TMEM100 acts as a TAK1 receptor that prevents pathological cardiac hypertrophy progression.

Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.

[Spatio-temporal Evolution and Driving Factors of Ecological Environment Quality in the Huaihe River Basin Based on RSEI].

Clarifying the spatio-temporal evolution of the ecological environment quality of a watershed and its response to the natural environment and human factors are crucial for policy implementation in the ecological environment of the watershed. Using the Google earth engine（GEE） to establish a remote sensing ecological index （RSEI）, the spatio-temporal changes in the ecological environment quality of the Huaihe River Basin from 2002 to 2022 were evaluated combined with trend analysis, variation coefficient, and Hurst index. The main driving factors of spatial differentiation of RSEI were explored using the geographic detector. The results showed that： ① In the past 21 years, RSEI of the Huaihe River Basin had generally improved, but it showed a gradual upward-downward trend. Overall, the area of poor and less poor grades decreased, the area of medium grades increased, and the area of good and excellent grades increased. The improved area accounted for 55.93%, and the degraded area accounted for 22.01%. ② In terms of spatial distribution, RSEI gradually deteriorated from east to west （except in the northwest and southwest marginal mountainous areas）. The stability was better in the east and worse in the western and central areas. In the future, the ecological quality change in the basin was prone to be anti-sustainable and mainly improved. ③ Factor detection results showed that the spatial differentiation of RSEI in the basin was mainly driven by vegetation factors, followed by altitude. The interaction between two factors enhanced the driving force for RSEI spatial differentiation, in which the interaction between vegetation factor and elevation had the strongest driving force for RSEI spatial differentiation, reaching 86.3%.

Short-term prognostic analysis of patients with systemic lupus erythematosus co-infection and comparison of mNGS and conventional microbiological test results.

Objectives: Infection is one of the major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE), and as a new diagnostic technique, metagenomic next-generation sequencing (mNGS) is increasingly used for the pathogenetic detection of co-infected SLE patients. However, conventional microbiological testing (CMT) is still the gold standard for pathogenic diagnosis, and the specific diagnostic efficacy of mNGS versus CMT in such patients is not known. In addition, there are few studies on the short-term prognosis of co-infected SLE patients. Methods: This study retrospectively included 58 SLE patients with co-infection admitted to the First Affiliated Hospital of Zhengzhou University from October 2020 to August 2022. Patients were divided into a survivors (n=27) and a non-survivors (n=31) according to their discharge status. Baseline characteristics and etiological data were collected and statistically analyzed for all patients during their hospitalization. The sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE) II and systemic lupus erythematosus disease activity index (SLEDAI) were calculated for each patient to assess the predictive ability of the 3 scores on the short-term prognosis of SLE patients. The mNGS and CMT culture results were also compared to clarify the flora characteristics of patients with SLE infection. Results: More patients in the non-survivors had renal impairment, neurological manifestations, multiplasmatic cavity effusion and gastrointestinal manifestations compared to the survivors (p < 0.05). The SOFA score, APACHE II and SLEDAI were significantly higher in the non-survivors than in the survivors (p < 0.01). There were also significant differences between the two groups in several tests such as hemoglobin, platelets, albumin, total bilirubin, C-reactive protein (CRP), procalcitonin (PCT), and complement C3 (p < 0.05). In addition, the absolute values of T lymphocytes, CD4+ T cells and CD8+ T cells were smaller in the non-survivors than in the survivors (p < 0.05). The most common type of infection in this study was pulmonary infection, followed by bloodstream infection. mNGS and CMT positivity rates were not significantly different among patients in the non-survivors, but were significantly different among patients in the survivors (p=0.029). In-hospital survival of patients with SLE infection could be predicted based on the SOFA score in relation to 6. For patients with SOFA <6, we recommend earlier mNGS testing to identify the pathogen and improve patient prognosis. Conclusions: For SLE patients with co-infection, in-hospital survival can be predicted based on SOFA score. For patients with SOFA <6, advising them to complete mNGS testing as early as possible may improve the prognosis to some extent.

Analysis of influencing factors for prognosis of patients with ventricular septal perforation: A single-center retrospective study.

Background: Ventricular septal rupture (VSR) is a type of cardiac rupture, usually complicated by acute myocardial infarction (AMI), with a high mortality rate and often poor prognosis. The aim of our study was to investigate the factors influencing the long-term prognosis of patients with VSR from different aspects, comparing the evaluation performance of the Gensini score, Sequential Organ Failure Assessment (SOFA) score and European Heart Surgery Risk Assessment System II (EuroSCORE II) score systems. Methods: This study retrospectively enrolled 188 patients with VSR between Dec 9, 2011 and Nov 21, 2021at the First Affiliated Hospital of Zhengzhou University. All patients were followed up until Jan 27, 2022 for clinical data, angiographic characteristics, echocardiogram outcomes, intraoperative, postoperative characteristics and major adverse cardiac events (MACEs) (30-day mortality, cardiac readmission). Cox proportional hazard regression analysis was used to explore the predictors of long-term mortality. Results: The median age of 188 VSR patients was 66.2 ± 9.1 years and 97 (51.6%) were males, and there were 103 (54.8%) patients in the medication group, 34 (18.1%) patients in the percutaneous transcatheter closure (TCC) group, and 51 (27.1%) patients in the surgical repair group. The average follow-up time was 857.4 days. The long-term mortality of the medically managed group, the percutaneous TCC group, and the surgical repair group was 94.2, 32.4, and 35.3%, respectively. Whether combined with cardiogenic shock (OR 0.023, 95% CI 0.001-0.054, P = 0.019), NT-pro BNP level (OR 0.027, 95% CI 0.002-0.34, P = 0.005), EuroSCORE II (OR 0.530, 95% CI 0.305-0.918, P = 0.024) and therapy group (OR 3.518, 95% CI 1.079-11.463, P = 0.037) were independently associated with long-term mortality in patients with VSR, and this seems to be independent of the therapy group. The mortality rate of surgical repair after 2 weeks of VSR was much lower than within 2 weeks (P = 0.025). The cut-off point of EuroSCORE II was determined to be 14, and there were statistically significant differences between the EuroSCORE II < 14 group and EuroSCORE II≥14 group (HR = 0.2596, 95%CI: 0.1800-0.3744, Logrank P < 0.001). Conclusion: Patients with AMI combined with VSR have a poor prognosis if not treated surgically, surgical repair after 2 weeks of VSR is a better time. In addition, EuroSCORE II can be used as a scoring system to assess the prognosis of patients with VSR.

[Estimating the climatic capacity of food security in Henan Province, China under the future climate change scenarios]. / æœªæ¥æ°”å€™å˜åŒ–æƒ æ™¯ä¸‹æ²³å—çœç²®é£Ÿå®‰å ¨æ°”å€™æ‰¿è½½åŠ›è¯„ä¼°.

To explore the effects of future climate change on food production in Henan Province, the climate potential productivity and its change characteristics in Henan Province were calculated by agro-ecological zone (AEZ) model. This study was based on the production potential and climate resource carrying capacity of summer maize and winter wheat, combined with the observation data of 111 meteorological stations in Henan Province from 1961 to 2017 and the meteorological data under two emission scenarios of RCP4.5 and RCP8.5 in 2041-2080. With the grain demand index under different living standards, we analyzed climate carrying capacity and surplus space of Henan Pro-vince. The results showed that the average climatic potential productivity of maize was 18408.87 kg·hm-2 from 1961 to 2017, with high values in the middle and east, and low values in the west. Compared with the reference period (1981-2010), climatic potential productivity of maize under RCP4.5 and RCP8.5 decreased by 13.0% and 8.0% respectively, with the high value center shifting from the east to the southwest of Henan. The average climatic potential productivity of wheat was 10889.79 kg·hm-2, which was high in the middle region and low in the north. Compared with the reference period, climatic potential productivity of wheat under RCP4.5 and RCP8.5 decreased by 18.6% and 21.7%, respectively. Under the current condition of subsistence and well-off food demand, the maximum carrying capacity of climate resources respectively could support 252 million and 183 million people. In 2070s (2071-2080), the average supporting population of the maximum climate resource carrying capacity (Cmax) would decrease. Compared with the reference period, Cmax under the level of well-off and subsistence would decrease by 9.7% and 18.4% respectively in RCP4.5 scenario, and 7.7% and 16.6% respectively in RCP8.5 scenario. Under current climate condition, the relative surplus rate of climate resources in Henan Province ranged from -93.0% to 356.9%. Compared with the reference period, the relative residual rate of climate resources in the future would reduce nearly 40%.

Stent-unsheathed effect predicts acute distal middle cerebral artery atherosclerotic disease-related occlusion.

BACKGROUND: The differentiation of intracranial atherosclerosis (ICAS) and embolism is important. OBJECTIVE: In cases of ICAS, we observe a phenomenon that we call the "post-stent-deployment effect"; that is, all major branches are clearly visible beyond the occlusion segment when the stent is deployed at the site of occlusion. Our objective is to evaluates whether this post-stent-deployment effect can be used to differentiate ICAS from embolism in the distal M1 segment occlusion. METHODS: We conduct a retrospective study which reviewed consecutive patients with acute distal M1 segment and in whom recanalization was achieved by endovascular treatment. The post-stent-deployment effect was assessed in these patients. The sensitivity, specificity, positive predictive values (PPV), and accuracy of the post-stent-deployment effect for prediction of ICAS were assessed. RESULTS: From January 2015 to July 2018, a total of 80 patients were evaluated. The post-stent-deployment effect was more frequently observed in patients with ICAS than in those with embolism (100% vs 15.0%, P < .001). For identifying ICAS in distal M1 segment, the sensitivity, specificity, PPV, and accuracy of the post-stent-deployment effect were 100%, 85.0%, 69.0%, and 88.7%, respectively. CONCLUSION: Our study finds that the sensitivity and accuracy of the post-stent-deployment effect in predicting distal M1 segment ICAS occlusion in patients with acute symptoms was high, and it may be useful in identifying ICAS lesion.

Clinical significance of common-stem lenticulostriate arteries in patients with internal watershed infarction.

BACKGROUND: A common-stem origin of lenticulostriate arteries (CS-LSAs) is an anatomical variation that supplies a moderate to large section of the basal ganglia. We hypothesized that CS-LSAs with a patent orifice are located at distal positions of the acute-occluded middle cerebral artery (MCA) and that the blood flow of CS-LSAs is supplied by pail arterial anastomoses and results in hypoperfusion of CS-LSAs, similar to a deep watershed (DWS) infarction. OBJECTIVE: Our study evaluated the possibility of CS-LSAs in patients with DWS infarction and MCA occlusion and also assessed the safety of endovascular therapy (ET) in these patients. METHODS: A cohort of consecutive patients with DWS infarction and MCA occlusion and in whom full recanalization via ET was achieved were identified. Patients were divided into two groups based on the presence of CS-LSAs observed during ET. In addition, radiological and clinical data were retrospectively analyzed. RESULTS: Thirty-three patients were included, and CS-LSAs were observed in 48.5% (16/33) of patients. The possibility (72.2%, 13/18) of CS-LSAs was high in patients with DWS infarction companied with basal ganglia infarction. A good clinical outcome was similar in patients with CS-LSAs and basal ganglia infarction and in patients without CS-LSAs and basal ganglia infarction (69.2% vs. 81.8%, P = 0.649). CONCLUSIONS: The possibility of CS-LSAs was 48.5% in patients with DWS infarction and MCA occlusion, and the revascularization procedure was safe and feasible in these patients despite the moderate-to-large basal ganglia infarction.

Association of copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein gene with the natural history in a Chinese spinal muscular atrophy cohort.

We evaluated survival motor neuron 2 (SMN2) and neuronal apoptosis inhibitory protein (NAIP) gene copy distribution and the association of copy number with survival in 232 Chinese spinal muscular atrophy (SMA) patients. The SMN2 and NAIP copy numbers correlated positively with the median onset age (r = 0.72 and 0.377). The risk of death for patients with fewer copies of SMN2 or NAIP was much higher than for those with more copies (P < .01). The survival probabilities at 5 years were 5.1%, 90.7%, and 100% for 2, 3, and 4 SMN2 copies and 27.9%, 66.7%, and 87.2% for 0, 1, and 2 NAIP copies, respectively. Our results indicated that combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age and poorer survival probability. Better survival status for Chinese type I SMA might due to a higher proportion of 3 SMN2 and a lower rate of zero NAIP.

[A study involving antioxidizability and cytotoxicity of two kinds of phenol from Ajania Salicifolia and their mechanisms of apoptosis].

OBJECTIVE: To extract two kinds of phenols 4-hydroxy-3, 5-dimethoxy-4-(2-oxopropyl) cyclohexa-2, 5-dien-l-one and 6-methoxy-5,7-dihydroxy coumarin (named as I and H compounds respectively) from Ajania salicifolia and to investigate their antioxidation and cytotoxicity to tumors and explore their pro-apoptosis mechanism. METHODS: The antioxidant activities of two compounds were assessed by ABTS and DPPH radical-scavenging assays. Two compounds were evaluated for their cytotoxicity against human chronic myelogenous leukemia (K562) cells using the MIT assay. The expression of NF-kappaB P65 mRNA in K562 apoptotic cells was measured by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR. In addition, protein expression levels of the NF-ICB P65, p-Akt, Fas, P-catenina and E-cadherin were also measured by Western blot. RESULTS: (1) We found that compound I displayed significant inoxidizability, while compound II had no obvious antioxidizability. (2) In cytotoxicity experiments, compound I didn't display cytotoxicity while compound H displayed obvious cytotoxicity. (3) Compared with the blank group, the expression of NF-kappaB P65 mRNA in K562 cell after treatment with compound II was obviously up-regulated. (4) Compared with the blank group, the expression levels of NF-kappaB P65, Fas, beta-catenina and E-cadherin were significantly increased in compound II treated groups and it appeared obvious dose-effect relationship between the expression of protein and drug concentration. CONCLUSION: Two phenols have obvious antioxidizability and cytotoxicity respectively. On the one hand, the tumor-suppressing mechanism of compound II maybe act by up-regulation the expression of NF-kappaB P65 and Fas protein; thereby, affecting the classical Fas apoptosis signaling pathways. On the other hand, it can also up-regulate the expression of protein beta-catenin and E-cadherin, which participate in the adhesion between cells, and accordingly, playing an important role in preventing the proliferation and metastasis of cancer cells.

Blood lead levels among children aged 0 to 6 years in 16 cities of China, 2004-2008.

BACKGROUND: The adverse health effects of lead for children under 6 years are well known. Studies to assess the lead exposure among children in China are small in sample size and lack of national representative data. The aim of this study therefore was to describe blood lead levels and identify risk factors for lead exposure among children aged 0 to 6 years living in 16 cities in China. METHODS: We analyzed data from blood lead levels surveillance in China carried out in 16 large cities between 2004 and 2008. A stratified clustered random sampling strategy was used. A total of 69 968 children aged 0 to 6 years were included. We conducted multiple Logistic regression analyses to explore risk factors to high blood lead level. RESULTS: The geometric mean blood lead level of the children was 4.50 µg/dl (median: 4.90 µg/dl; IQR: 3.20 - 7.00 µg/dl). Overall prevalence of blood lead level ≥ 10.00 µg/dl among 0- to 6-year-old children was 7.57%. But the proportion of blood lead level ≥ 5.00 but < 10.00 µg/dl was 42.12%. Blood lead levels were significantly higher in boys (4.63 µg/dl) than in girls (4.35 µg/dl) (P < 0.0001). The geometric mean blood lead levels and prevalence of blood lead level ≥ 10.00 µg/dl increased with age (P < 0.0001 for the two trends). After controlling for sociodemographic, dietary and behavior factors, multivariable analysis indicated that lower maternal education, male gender, younger age, often biting pencil or/and toys, walking or playing for long time on the street, not washing hands before eating are major risk factors for higher lead levels. CONCLUSIONS: The blood lead levels among Chinese children in urban areas are lower than previous studies but close to those of developed countries. However, children with low lead exposure account for almost half and the sociodemographic factors (age, male sex, and low mother education level) continue to be associated with higher blood lead levels.

Common underlying diseases do not contribute in determining the causes of sudden unexplained death.

BACKGROUND: Underlying diseases have a statistically significant positive correlation to sudden death. However, sudden unexplained death (SUD) is different from sudden death, as there is no clinical evidence to support the sudden death due to the original underlying disease, nor a lethal pathological basis to be found during autopsy. In addition, SUD are more common in young, previously healthy individuals, usually without any signs of disease, with no positive lesions found after autopsy. Therefore, a causal relationship between SUD and the underlying disease needs to be further explored. This study aimed to explore the role that common underlying diseases play in patients with SUD and to reveal the correlation between them. METHODS: The medical records, history and case information of 208 patients with SUD were collected for the survey. All these SUD occurred in the emergency room of Peking University Third Hospital from January 2006 to December 2009. The patients were stratified by with and without common underlying diseases. To examine possible associations between the underlying diseases and the cause of unexplained sudden death, the chi-squared and Fisher's exact tests were used. RESULTS: Among the 208 patients, 65 were diagnosed with common underlying diseases while 143 were not. Within these two groups, there were 45 patients for whom the clear cause of death was determined. However, there were no statistically significant differences or strong associations (χ(2) = 1.238, P > 0.05) between the 11 patients with (16.90%) and 34 without (23.78%) common underlying disease among these 45 patients. We also found that occurrence of the common underlying diseases, such as neurological system, cardiovascular and pulmonary system diseases, are not statistically significant (P > 0.05) in the diagnosis of the SUD. CONCLUSION: Common underlying diseases make no obvious contributions to SUD and are not useful in diagnosing the underlying reasons for death.

Analysis of the prodromal symptoms of unexplained sudden death in patients with or without underlying diseases.

BACKGROUND: In recent years, the incidence of unexplained sudden death has risen significantly across the world. However, it occurred suddenly, often in young apparently healthy individuals and almost 50% of the patients did not have any warning signals or symptoms. Therefore, the prodromal symptoms before the incident are extremely important for early prediction of sudden death. In this article, we aimed to explore the value of prodromal symptoms for unexplained sudden death and whether the prodromal symptoms have a predictive function to unexplained sudden death (USD) without underlying diseases. METHODS: A total of 208 sudden death cases were selected for the survey in the Emergency Department of Peking University Third Hospital from January 2006 to December 2009 and their medical records were reviewed. The patients were divided into two groups, 65 patients had underlying diseases while 143 had not underlying diseases. In the meantime, their prodromal symptoms were collected and compared, prodromal symptoms including chest distress, dyspnea, syncope, fever, headache, vomiting, etc. RESULTS: Patients with underlying diseases were compared to those without underlying diseases associated with sudden death; there was no significant difference in gender and age distribution. Among the 208 cases, 39 cases (18.75%) had prodromal symptoms, patients with underlying diseases had prodromal symptoms in 12 cases (18.46%), while patients without underlying diseases had prodromal symptoms in 27 cases (18.88%). The difference between the two groups with prodromal symptoms was not statistically significant (P > 0.05). CONCLUSIONS: Prodromal symptoms are extremely important warning signals in the occurrence of USD. It has equally important predictive value for patients both with and without underlying diseases, especially in predicting sudden death caused by cardiopulmonary and neurological diseases.

Effect of centrally administered C75, a fatty acid synthase inhibitor, on gastric emptying and gastrointestinal transit in mice.

The central or systemic administration of 3-carboxy-4-octyl-2-methylenebutyrolactone (C75), a synthetic inhibitor of fatty acid synthase (FAS), causes anorexia and profound weight loss in rodents. The amount of food intake and gastrointestinal mobility are closely related. In this study, an attempt has been made to investigate the effects and mechanisms of C75 on gastric emptying and gastrointestinal transit after intracerebroventricular (i.c.v.) injection in mice. Our data showed that C75 (1, 5, 10 microg/mouse) dose-dependently delayed gastric emptying and gastrointestinal transit in fasted mice. 10 microg C75 delayed gastric emptying by about 21.4% and reduced gastrointestinal transit by about 31.0% compared with vehicle control group. Administration (i.c.v.) of 5-(tetradecyloxy)-2-furoic acid (TOFA, an acetyl-CoA carboxylase (ACC) inhibitor) or ghrelin attenuated the delayed gastrointestinal mobility effect induced by 10 microg C75. Taken together, C75 is able to decrease gastrointestinal mobility and it seems possible that malonyl-CoA and ghrelin might play an intermediary role in these processes.

[Estimation of chemical fertilizer N-induced direct N2O emission from China agricultural fields in 1991-2000 based on GIS technology].

Referring to the definition of agricultural field N2O emission factor by the Intergovernmental Panel on Climate Change, the main controlling factors climate and cropping system were introduced to estimate the chemical fertilizer N-induced direct N2O emission from China agricultural fields in 1991-2000, and a spatial inventory with 10 km x 10 km resolution was developed by dint of GIS framework. The results indicated that there was an increasing trend in the annual direct N2O emission, due to the increasing input of chemical fertilizer N. The mean annual emission in 1990s was estimated to be 204 Gg N2O-N, ranging from 159 to 269 Gg N2O-N, and the lowest and the highest emission occurred in 1992 and 1998, respectively. The uncertainty of the estimation was quantified to be about 23%. The spatial distribution of N2O emission was characterized by higher flux in eastern China and lower flux in western China, which was mainly attributed to the application rate of chemical fertilizer N and precipitation.