[Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study].

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

Bradyrhizobium arachidis mediated enhancement of (oxy)matrine content in the medicinal legume Sophora flavescens.

Effect of rhizobial inoculation and nitrate application on the content of bioactive compounds in legume plants is an interesting aspect for interactions among microbes, plants and chemical fertilizers, as well as for cultivated practice of legumes. In this study, nitrate (0, 5 and 20 mmol l-1 ) and Bradyrhizobium arachidis strain CCBAU 051107T were applied, individually or in combination, to the root rhizosphere of the medicinal legume Sophora flavescens Aiton (SFA). Then the plant growth, nodulation and active ingredients including (oxy)matrine of SFA were determined and compared. Rhizobial inoculation alone significantly increased the numbers and fresh weight of root nodules. Nodulation was significantly inhibited due to nitrate (5 and 20 mmol l-1 ). Only oxymatrine was detected in the control plants without rhizobial inoculation and nitrate supplement, while both oxymatrine and matrine were synthesized in plants treated with inoculation of B. arachidis or supplied with nitrate. The content of oxymatrine was the highest in plants inoculated solely with rhizobia and was not significantly altered by additional application of nitrate. Combinations of B. arachidis inoculation and different concentrations of nitrate did not significantly change the concentrations of (oxy)matrine in the plant. In conclusion, sole rhizobial inoculation was the best approach to increase the contents of key active ingredients oxymatrine and matrine in the medicinal legume SFA.

[Analysis on the trend of overweight and obesity of children and adolescents in 9 provinces of China from 1991 to 2015].

Objective: To analyze the trends of overweight and obesity of children and adolescents in 9 provinces of China from 1991 to 2015. Methods: A total of 14 888 children and adolescents aged 6-17 years with complete data were selected from the China Health and Nutrition Survey from 1991 to 2015. The definitions of overweight and obesity were defined using the international body mass index (BMI) cut-offs for child overweight and obesity established by the International Obesity Task Force in 2000 (hereinafter referred to as 'IOTF Standard'), the growth reference for school-aged children and adolescents established by the World Health Organization in 2007 (hereinafter referred to as 'WHO Standard'), the BMI cut-offs for screening overweight and obesity in Chinese children established by Li Hui et al. in 2009 (hereinafter referred to as 'Expert Standard'), and the screening thresholds for overweight and obesity in Chinese school-age children and adolescents released by the National Health and Family Planning Commission in 2018 (hereinafter referred to as 'Industry Standard'). Multivariable linear regression model was used to examine the trends in BMI values from 1991 to 2015, and multivariable logistic regression model was used to examine the trends in the prevalence of overweight and obesity from 1991 to 2015. Results: After adjusting for the age, sex and region, BMI values increased from 17.26 kg/m(2) in 1991 to 18.72 kg/m(2) in 2015 (P value for trend <0.001). The prevalence of overweight defined by the IOTF Standard, WHO Standard, Expert Standard, and Industry Standard increased from 4.06%, 5.37%, 5.16%, and 4.27% in 1991 to 13.58%, 16.23%, 13.30%, and 11.70% in 2015, respectively (all P values for trend <0.001), and the prevalence of obesity increased from 1.02%, 1.86%, 2.24%, and 2.41% in 1991 to 7.45%, 10.75%, 12.08%, and 12.74% in 2015, respectively (all P values for trend <0.001). Conclusion: The BMI values and prevalence of overweight and obesity increased significantly in Chinese children and adolescents from nine provinces from1991 to 2015.

Broadband Terahertz Generation via the Interface Inverse Rashba-Edelstein Effect.

Novel mechanisms for electromagnetic wave emission in the terahertz frequency regime emerging at the nanometer scale have recently attracted intense attention for the purpose of searching next-generation broadband THz emitters. Here, we report broadband THz emission, utilizing the interface inverse Rashba-Edelstein effect. By engineering the symmetry of the Ag/Bi Rashba interface, we demonstrate a controllable THz radiation (∼0.1-5 THz) waveform emitted from metallic Fe/Ag/Bi heterostructures following photoexcitation. We further reveal that this type of THz radiation can be selectively superimposed on the emission discovered recently due to the inverse spin Hall effect, yielding a unique film thickness dependent emission pattern. Our results thus offer new opportunities for versatile broadband THz radiation using the interface quantum effects.

Genetic diversity and population structure analysis in Perilla frutescens from Northern areas of China based on simple sequence repeats.

In this study, 21 simple sequence repeat (SSR) markers were used to evaluate the genetic diversity and population structure among 77 Perilla accessions from high-latitude and middle-latitude areas of China. Ninety-five alleles were identified with an average of 4.52 alleles per locus. The average polymorphic information content (PIC) and genetic diversity values were 0.346 and 0.372, respectively. The level of genetic diversity and PIC value for cultivated accessions of Perilla frutescens var. frutescens from middle-latitude areas were higher than accessions from high-latitude areas. Based on the dendrogram of unweighted pair group method with arithmetic mean (UPGMA), all accessions were classified into four major groups with a genetic similarity of 46%. All accessions of the cultivated var. frutescens were discriminated from the cultivated P. frutescens var. crispa. Furthermore, most accessions of the cultivated var. frutescens collected in high-latitude and middle-latitude areas were distinguished depending on their geographical location. However, the geographical locations of several accessions of the cultivated var. frutescens have no relation with their positions in the UPGMA dendrogram and population structure. This result implies that the diffusion of accessions of the cultivated Perilla crop in the northern areas of China might be through multiple routes. On the population structure analysis, 77 Perilla accessions were divided into Group I, Group II, and an admixed group based on a membership probability threshold of 0.8. Finally, the findings in this study can provide useful theoretical knowledge for further study on the population structure and genetic diversity of Perilla and benefit for Perilla crop breeding and germplasm conservation.

Financial burden on the families of patients with hepatitis B virus-related liver diseases and the role of public health insurance in Yunnan province of China.

OBJECTIVE: To investigate the financial burden of patients who had various stages of hepatitis B virus-related diseases and the level of alleviation from financial burden by health insurance schemes in Yunnan province of China. STUDY DESIGN: A cross-sectional survey. METHODS: Patients' information was consecutively recorded at the First Affiliated Hospital of Kunming Medical University, from December 2012 to June 2013. Consecutive cases of hepatitis B virus (HBV) (520), compensated cirrhosis (91), decompensated cirrhosis (198) and hepatocellular carcinoma (HCC) (131) were recruited from the outpatient and inpatient departments. The total direct costs, hospital charge, outpatient costs, hospitalization fees being reimbursed and household catastrophic health expenditure were estimated for each disease group. RESULTS: The average annual direct costs for each disease group were 19,496 RMB for HBV, 28,466 RMB in compensated cirrhosis, 46,061 RMB for decompensated cirrhosis, and 33,044 RMB for HCC patients. Catastrophic health expenditure occurred in all four groups. Health insurance reimbursement released the financial burden incurred by medical expenses of patients under a high level of household economic status. Public health insurance schemes helped the patients to various extents. CONCLUSIONS: Among these patient groups, direct costs represent a significant economic burden. Health expenditure and financing systems must be considered to prevent the increase of household catastrophe, particularly among the poor.

Efficacy and safety of keto-supplemented low-protein diet on nutritional status of peritoneal-dialysis patients: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this meta-analysis is to evaluate the efficacy of a keto-supplemented low-protein diet (sLPD) in enhancing nutritional status among individuals undergoing peritoneal dialysis (PD) compared to a low-protein diet (LPD). MATERIALS AND METHODS: Studies from PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched and reviewed up to January 2023. Randomized controlled trials (RCTs) were enrolled and analyzed using STATA MP 17. In this review, serum albumin (Alb), body mass index (BMI), and serum prealbumin (PA) were included for efficacy evaluation and serum calcium (CA) for safety evaluation. Potential heterogeneity was detected using subgroup analyses. RESULTS: 7 RCTs were included. Compared with LPD, sLPD can improve the Alb [Weighted Mean Difference (WMD)=4.16; 95% CI: 2.50, 5.83; p<0.0001), BMI [WMD=1.35; 95% CI: 0.59, 2.11; p<0.0001] and PA [WMD=0.07; 95% CI: 0.04, 0.10; p<0.0001] level of patients undergoing PD. Subgroup analyses showed that, although Alb had no difference with LPD within 12 months of PD duration, sLPD treatment could improve the levels of Alb and PA regardless of PD duration or course of treatment. sLPD can improve the BMI of patients with a PD duration of more than 24 months, regardless of the duration of treatment. CONCLUSIONS: A sLPD is an effective intervention for improving the nutritional status of PD patients. It is suggested that patients undergoing PD should initiate sLPD at the beginning of PD to ensure sufficient nutritional intake.

The effects of computer-aided cognitive rehabilitation combined with virtual reality technology on event-related potential P300 and cognitive function of patients with cognitive impairment after stroke.

OBJECTIVE: The aim of this study was to explore the effects of computer-aided cognitive rehabilitation (CACR) combined with virtual reality (VR) technology on event-related potential P300 and cognitive function in patients with cognitive impairment after stroke. PATIENTS AND METHODS: Clinical data from 94 patients with post-stroke cognitive impairment, admitted to our hospital from January 2020 to March 2023, were retrospectively analyzed. Of them, 45 patients received routine rehabilitation training (Control group), and 49 patients received CACR combined with VR technology (Observation group). Cognitive rehabilitation status, event-related potential P300 examination status, biochemical indices levels, and daily living activity scores of the two groups were evaluated and compared. RESULTS: After treatment, cognitive function significantly improved in the Observation group compared to the Control group. The amplitude of P300 in the Observation group was significantly higher, and the latency was significantly lower compared to the Control group. The levels of brain-derived neurotrophic factor (BDNF) in the Observation group were significantly higher (p<0.05), while the levels of cystatin C (Cys-C) and neuron-specific enolase (NSE) were significantly lower than those in the Control group (p<0.05 each). Patients in the Observation group demonstrated a significantly higher ability to perform daily living activities compared to the Control group (p<0.05). CONCLUSIONS: Compared with conventional rehabilitation training, the combination of CACR and VR technology in the treatment of stroke-induced cognitive impairment is more effective in improving patients' cognitive function, regulating BDNF, Cys-C, and NSE levels, and enhancing patients' ability to perform daily living activities.

Proteomic study on CUMS-induced senile depression mice's frontal lobe cortex and the regulating effect of KTLD formula.

OBJECTIVE: The aim of this study was to investigate the protein expression of chronic unpredictable mild stress (CUMS)-induced senile depression in SAMP-8 mice's frontal lobe cortex and the regulating effect of the kidney tonifying and liver dispersing (KTLD) formula. MATERIALS AND METHODS: A total of 15 male SAMP-8 mice were randomly divided into control, CUMS, and KTLD groups. CUMS and KTLD mice were subjected to CUMS for 21 days. Control group mice were kept to normal feeding. At the same time as molding, the herbal gavage (KTLD formula, 19.5 g/kg/d) was given from the beginning of the stress stimulation, while the control group and the CUMS group mice were given the same volume of saline for 21 days. Open-field testing (OFT) was used to assess the mice's depression levels. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify differentially expressed proteins (DEPs) in mice's frontal lobe cortex. Bioinformatics analysis including Gene Ontology (GO); Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) networks were utilized to study the DEPs connections. RESULTS: Results revealed that mice with senile depression experienced more anxiety and depression than control mice, whereas KTLD mice had the opposite experience. Biological processes including transport, regulation of transcription, and DNA-templated were identified in both KTLD and CUMS. The KEGG enrichment study of the DEPs in KTLD revealed their involvement in the MAPK signaling pathway, glutamatergic synapse, dopaminergic synapse, axon guidance, and ribosome. KEGG pathway enrichment showed that the mechanism of senile depression and the pathway of KTLD are closely related to axonal conductance and ribosomes. According to the PPI analysis, disease-related proteins regulated by KTLD revealed that some proteins, such as GLOI1 and TRRAP, have potential interactions. This provides fresh insight into how KTLD works to cue senile depression. CONCLUSIONS: KTLD treats senile depression via multiple targets and pathways, which may include regulations of 467 DEPs. Proteomics showed significant changes in protein levels in geriatric depression and after KTLD intervention. Senile depression involves the cross-linking and modulation of signal pathways, presenting a pattern of multiple pathways and multiple targets. According to a protein pathway enrichment and protein interaction model of KTLD in senile depression, KTLD is capable of treating senile depression via multiple pathways and targets.

[Association between periodontitis and mild cognitive impairment: a clinical pilot study].

Objective: To evaluate the association between periodontitis and mild cognitive impairment (MCI), and explore the potential local oral risk factors for MCI. Methods: The study included 70 middle-aged and elderly subjects (44 females and 26 males) with periodontal disease who were first diagnosed by the Department of Periodontology or referred by the Department of Geriatrics in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2021 to January 2022. In this study, the control group consisted of periodontal disease patients without cognitive impairment, and the case group (MCI group) consisted of those diagnosed with MCI referred by the geriatrics specialists. Full-mouth periodontal examinations of all subjects were performed and periodontal indicators were recorded by periodontists, while digital panoramic radiographs were taken. The severity of periodontitis was defined according to the 1999 classification, and the staging and grading of periodontitis were defined according to the 2018 American Academy of Periodontology and European Federation of Periodontology classification. The mini-mental state examination scale was chosen by geriatricians to evaluate the cognitive function of the included subjects. The cubital venous blood was drawn to detect the expression levels of inflammatory factors such as hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α(TNF-α) in serum. Independent-samples t test and chi-square test were used to analyze the differences in population factors, periodontal-related indexes and serum inflammatory factors between the two groups (α=0.05). Odds ratios (OR) for MCI according to the severity of periodontitis and main periodontal clinical indexes were calculated by binary Logistic analysis. Results: Thirty-nine subjects were included in the control group and thirty-one in the MCI group. The age of the study population was (58.3±6.2) years (range: 45-70 years). The comparison between two groups showed that the control group was with higher educational background (χ²=9.45, P=0.024) and 2.6 years younger than the MCI group [(57.1±6.0) years vs. (59.7±6.3) years, t=-1.24, P=0.082]. The number and proportion of moderate to severe periodontitis in control group were significantly lower compared to those in MCI group (17 cases with 43.6% vs. 23 cases with 74.2%, χ²=6.61, P=0.010), and the OR of moderate to severe periodontitis adjusted by age and educational background was 3.00 (95%CI: 1.01-8.86, P=0.048). Compared with the grading (χ²=5.56, P=0.062) of periodontitis, staging had a greater impact on MCI (χ²=7.69, P=0.041), moreover the proportion of MCI in stage Ⅰ grade A periodontitis was significantly lower than any other type of periodontitis (χ²=13.86, P=0.036). In addition, less presence of deep periodontal pockets [probing depth (PD)≥6 mm] (17.9% vs. 41.9%, χ²=4.87, P=0.027), fewer number of PD≥4 mm (6.48±6.70 vs. 11.03±8.91, t=-2.44, P=0.017), lower plaque index (1.42±0.56 vs. 1.68±0.57, t=-1.91, P=0.059) and gingival index (1.68±0.29 vs. 1.96±0.30, t=-3.93, P<0.001) were in the control group than in the MCI group. However, there were no significant differences between the two groups in the levels of serum inflammatory factors, such as hs-CRP, IL-1ß, IL-6 and TNF-α (P>0.05). Conclusions: It appears a strong correlation between moderate to severe periodontitis and the incidence of MCI in middle-aged and elderly people. Moreover, deep and increased number of periodontal pockets, poor oral hygiene, and severe gingival inflammation can be potentially associated risk factors for MCI.

[Changing trends in the levels of blood pressure and prevalence of hypertension among Chinese children and adolescents from 1991 to 2015].

Objective: To examine the trends in blood pressure levels and prevalence of hypertension among Chinese children and adolescents aged 7-17 years from 1991 to 2015, using the four blood pressure references for children and adolescents, in order to provide basic data for the prevention and control of hypertension. Methods: A total of 14 622 children and adolescents aged 7-17 years were selected from the China Health and Nutrition Survey 1991-2015. Hypertension was defined under the four latest published references including the 2018 Health Industry pediatric blood pressure reference (Industry Reference), the 2018 Chinese Hypertension Prevention and Treatment Guideline reference (Guideline Reference), the 2016 International Child Blood Pressure Reference (International Reference), and the 2017 Blood Pressure Reference by the American Academy of Pediatrics (US Reference). Multivariable liner regression model was used to examine the trends in blood pressure levels from 1991 to 2015, and multivariable logistic regression model was used to examine the trend in prevalence of hypertension from 1991 to 2015. Results: After adjusted for factors as age, sex, region, and BMI, the SBP appeared an increase, from 96.1 mmHg in 1991 to 102.7 mmHg and DBP from 62.6 mmHg to 67.4 mmHg (all P for trend <0.001) in 2015. The prevalence rates of hypertension defined by Industry Reference, Guideline Reference, International Reference and US Reference increased from 5.7%, 8.9%, 4.4% and 8.1% in 1991, to 12.8%, 20.5%, 13.1% and 17.8% (all P for trend <0.001) in 2015, respectively. Conclusion: Both levels of blood pressure and the prevalence of hypertension increased significantly in Chinese children and adolescents from 1991 to 2015.

The prevalence of household second-hand smoke exposure and its correlated factors in six counties of China.

OBJECTIVE: To study the prevalence of, and discuss factors contributing to, household second-hand smoke exposure in six counties in China, providing scientific support for the need to establish tobacco control measures in these areas. METHODS: A cross-sectional survey was performed. Investigators conducted face-to-face interviews using a standardised questionnaire to collect information on demographics, passive smoking behaviours and knowledge, and attitudes towards tobacco control. The setting was six counties from the three provinces: Mianzhu and Xichong counties in Sichuan Province; Anyi and Hukou counties in Jiangxi Province; and Xinan and Yanshi counties in Henan Province. A total of 8142 non-smokers (aged 18-69) in 2004 were included in the data analysis. Household second-hand smoke exposure rate as defined as the proportion of household passive smokers in the non-smoker population was used as the measure of household second-hand smoke exposure. RESULTS: The analysis of 8142 non-smokers revealed that, in these selected counties, the household second-hand smoke exposure rate was 48.3%. Respondents had positive attitudes towards tobacco control. Of 6972 respondents, 84.4% supported all the three tobacco control policies (banning smoking in public places, banning the selling of cigarettes to minors, banning all cigarette advertisements). In 3165 families with smokers, 87.2% of respondents reported that smokers would smoke in front of them. In 2124 families with smokers and children, 76.5% of respondents reported that smokers would smoke in front of children. As many as 42.1% of non-smokers would offer cigarettes to their guests, and only 46.8% of respondents would ask smokers to smoke outdoors. Only 6.3% of families completely forbade smoking at home. Multivariate logistic regression analysis revealed high second-hand smoke exposure for the following demographic groups: Jiangxi Province inhabitants, females, those with low education level, farmers and married respondents. CONCLUSIONS: Household second-hand smoke exposure rates in the selected counties were high. A high percentage of respondents reported that smokers would smoke in front of them and children. The pressure from non-smokers against smoking was relatively low, although offering cigarette was prevalent. Households that were completely smoking-free were rare, Further studies on these correlated factors could help us establish effective measures to reduce household second-hand smoke exposure.

[A new mediation analysis method for multiple mediators].

Mediation analysis is mainly used to explore the causal mechanism between independent variable X and dependent variable Y. It determines whether mediator M plays a role and evaluate the role's degree in the causal path by decomposing the causal path between the independent variable X and the dependent variable Y. However, the classical mediation analysis is generally used for single mediator. This paper introduces a new mediation analysis method for multiple mediators.

The cloning and characterization of a soluble epoxide hydrolase in chicken.

The mammalian soluble epoxide hydrolase (sEH) plays a role in the regulation of blood pressure and vascular homeostasis through its hydrolysis of the endothelial-derived messenger molecules, the epoxyeicosatrienoic acids. This study reports the cloning and expression of a sEH homolog from chicken liver. The resulting 63-kDa protein has an isoelectric point of 6.1. The recombinant enzyme displayed epoxide hydrolase activity when assayed with [3H]-trans-1,3-diphenylpropene oxide (t-DPPO), as well as trans-9,10-epoxystearate and the cis-8,9-, 11,12-, and 14,15- epoxyeicosatrienoic acids. The chicken enzyme displayed a lower kcat:Km for t-DPPO than the mammalian enzymes. The enzyme was sensitive to urea-based inhibitors developed for mammalian sEH. Such compounds could be used to study the role of chicken sEH in conditions in which endothelial-derived vasodilation is believed to be impaired, such as pulmonary hypertension syndrome.

Inactivated Pseudomonas aeruginosa inhibits hypoxia-induced pulmonary hypertension by preventing TGF-ß1/Smad signaling.

Pseudomonas aeruginosa is one of the common colonizing bacteria of the human body and is an opportunistic pathogen frequently associated with respiratory infections. Inactivated P. aeruginosa (IPA) have a variety of biological effects against inflammation and allergy. Transforming growth factor-ß (TGF-ß) signaling plays a critical role in the regulation of cell growth, differentiation, and development in a wide range of biological systems. The present study was designed to investigate the effects of IPA on TGF-ß/Smad signaling in vivo, using a hypoxia-induced pulmonary hypertension (PH) rat model. Sprague Dawley rats (n=40) were exposed to 10% oxygen for 21 days to induce PH. At the same time, IPA was administered intravenously from day 1 to day 14. Mean pulmonary artery pressure (mPAP) and the right ventricle (RV) to left ventricle plus the interventricular septum (LV+S) mass ratio were used to evaluate the development of PH. Vessel thickness and density were measured using immunohistochemistry. Primary arterial smooth muscle cells (PASMCs) were isolated and the proliferation of PASMCs was assayed by flow cytometry. The production of TGF-ß1 in cultured supernatant of PASMCs was assayed by ELISA. The expression levels of α-smooth muscle actin (α-SMA), TGF-ß1 and phospho-Smad 2/3 in PASMCs were assayed by western blot. Our data indicated that IPA attenuated PH, RV hypertrophy and pulmonary vascular remodeling in rats, which was probably mediated by restraining the hypoxia-induced overactive TGF-ß1/Smad signaling. In conclusion, IPA is a promising protective treatment in PH due to the inhibiting effects on TGF-ß1/Smad 2/3 signaling.

Targeted hsp70.1 disruption increases infarction volume after focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: Heat-shock proteins (HSPs) are highly conserved proteins that are induced by a variety of stresses. HSP70 is a 70-kDa HSP family known to have cytoprotective effects against various insults. The role of HSP70 in cerebral ischemia remains to be elucidated in vivo. METHODS: To investigate the effect of reduced HSP70 levels on cerebral ischemia, focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery was induced in hsp70.1 knockout mice. The expressions of hsp70.1 and hsp70.3 mRNAs and HSP70 protein were determined, and infarction volumes were measured and compared. RESULTS: Northern blots confirmed the absence of hsp70.1 mRNA expression in the knockout mice. The mean infarction volume was significantly larger in hsp70.1 knockout mice (92.5+/-8.3 mm(3)) than in the wild-type mice (59.3+/-8.9 mm,(3) P<0.001). Western blots showed increased HSP70 expression in the ischemic hemisphere in both knockout and wild-type mice, but HSP70 expression levels in knockout mice were significantly lower than those in their wild-type littermates. Immunohistochemistry did not show any significant differences between the knockout and wild-type animals and showed increased HSP70 immunoreactivity in the ischemic hemisphere, with predominance in the cerebral cortex, especially in the penumbra. CONCLUSIONS: Our results suggest that hsp70.1 plays an important role in the early protection of the brain, at least after acute focal cerebral ischemia in mice.

The (3R,9R)-3-hydroxy-7,8-dihydro-beta-ionol disaccharide glycoside is an aroma precursor in tea leaves.

The disaccharide glycoside, (3R,9R)-3-hydroxy-7,8-dihydro-beta-ionyl 6-O-beta-D-apiofuranosyl-beta-D-glucopyranoside was isolated as an aroma precursor from the leaves of Camellia sinensis var. sinensis cv. Yabukita. Its stereochemistry was elucidated on the basis of spectral data and chemical synthesis.

Dopamine 4-sulfate: effects on isolated perfused rat heart and role of atria.

We studied the effects of sulfate conjugate of dopamine on the isolated perfused rat heart (Langendorff preparation). In the experimental group, we removed atria from half number of the hearts. In the hearts with intact atria, dopamine 4-sulfate significantly improved the DT (developed tension), +dT/dt max (maximal rate of contraction), -dT/dt max (maximum rate of relaxation) over baseline values. But when atria were removed, dopamine 4-sulfate had no effect on the mechanical functions of heart. We analysed the effluent perfusate for the free and conjugated catecholamines. In the control group (no drug), and when atria were excised, the free catecholamine levels were negligible. But when the atria were kept intact, the effluent contained significant amount of free dopamine (DA), and norepinephrine (NE). These data suggested that dopamine sulfate had no direct effect on the ventricular muscle of rat heart, but was converted within the atrial tissues into free catecholamines which might be responsible for the positive inotropic actions.

Plasma levels of cyclic nucleotides in chronic congestive heart failure and their clinical implication.

Plasma levels of cyclic nucleotides were determined by radioimmunoassay in 196 cardiac patients and 50 normal persons. Plasma levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) increased with the deterioration of cardiac function. The level of cGMP was correlated with the cardiothoracic ratio, ratio of pre-ejection period and left ventricular ejection time, the intracardiac diameter, left ventricular ejection fraction and left ventricular short axis shortening (r = 0.55, r = 0.50, r = 0.55, r = -0.53 and r = -0.50, respectively; P < 0.001). There were only weak correlations between the level of cAMP and the cardiothoracic ratio, the ratio of pre-ejection period and the left ventricular ejection time, left ventricular ejection fraction, and left ventricular short axis shortening (r = 0.35, r = 0.38, r = -0.28 and r = -0.31, respectively; P < 0.01). The correlations between cGMP and mean pulmonary artery pressure (r = 0.48; P < 0.05) and mean left atrial pressure (r = 0.55; P < 0.01) were also significant. In patients who had received cardioversion and valve replacement the plasma cGMP level decreased significantly. During the follow-up period, 29 of 108 patients died (26.9%), the initial plasma levels of cAMP and cGMP in the dead group were significantly higher than those in the survival group (27.41 +/- 1.13 and 31.11 +/- 3.33 vs. 21.56 +/- 0.60 and 17.45 +/- 1.05 nmol/l, respectively; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)