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Abstract Vertical stratification of forest plays important roles in the local material balance and in maintaining forest health by distributing and redistributing precipitation materials through adsorption, fixation, and release. Differences in runoff nutrient concentrations among vertical layers are closely related to vertical stratification (factors such as the trunk, canopy, forest litter, and soil physical and chemical properties). Long-term forest observations revealed significant spatial differences in Pinus massoniana (Pinus massoniana Lamb.) forests in the Three Gorges Reservoir area. Pinus massoniana forests on downslopes were characterized by a dense canopy, green needles, and rich forest vegetation, while those on upslopes were characterized by low vegetation cover, dead trees, and decreases in the tree height, diameter at breast height, and volume per plant with increasing slope. By analyzing the soil at different sites, we found that the pH of the forest land soil differed significantly among different slope positions. Soil on upper slopes was significantly more acidic than soil on lower slopes, indicating that acidic substances were intercepted by filtration through the broad litter layer and the soil surface layer. This filtration process resulted in a normal rhizosphere environment suitable for the absorption of nutrients by vegetation on the lower slopes. In this way, downhill sites provided a good microenvironment for the growth of Pinus massoniana and other vegetation. Our results show that direct contact between needles and acid rain was not the main cause of root death. Instead, the redistribution of rainfall substances by forest spatial stratification caused changes in the soil microenvironment, which inhibited the absorption of nutrients by the roots of Pinus massoniana and the growth of understory plants in Pinus massoniana forests on upper slopes. These findings emphasize that increasing land cover with forests with vertical structural stratification plays an important role in woodland material redistribution and forest conservation.

Abstract The effect of serum glucose-to-potassium ratio (GPR) on cerebrovascular diseases has been previously validated. However, the value of the GPR in patients with severe intracerebral hemorrhage (ICH) requiring ICU admission remains unclear. This study aimed to investigate the association between the GPR and the clinical prognosis of critically ill patients with ICH. This study identified patients with severe ICH requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database and divided them into quartiles based on GPR levels. Outcomes included 30-day, 90-day, and 1-year mortality rates. The association between the GPR and clinical outcomes in critically ill patients with ICH was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. In total, 2018 patients (53.8% male), with a median age of 70 years, were enrolled in the study. The 30-day, 90-day, and 1-year mortality rates were 23.9%, 30.1%, and 38.4%, respectively. Per multivariate Cox proportional hazards analysis, an elevated GPR was significantly associated with all-cause mortality. After adjusting for age, sex, Charlson Comorbidity Index, white blood cell count, red blood cell count, platelet count, and Glasgow Coma Scale, patients with an elevated GPR had a higher 30-day mortality (hazard ratio [HR]: 1.32; 95% confidence interval [CI]: 1.22–1.42; P

Abstract Background Hyperglycemia upon admission is associated with poor prognosis of many cardiovascular diseases. However, the relationship of stress hyperglycemia ratio (SHR), admission blood glucose (ABG), and hemoglobin A1c (HbA1c) with pulmonary hypertension has not been reported. This study aimed to explore the association of hyperglycemia indices with disease severity and long-term adverse outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods This multi-center cohort study included 625 consecutive patients diagnosed with or treated for IPAH between January 2015 and June 2023. SHR was calculated using the followings: ABG (mmol/L)/(1.59 × HbA1c [%] − 2.59). The primary endpoint was defined as clinical worsening events. Multivariable Cox regression and restricted cubic spline analyses were employed to evaluate the association of SHR, ABG, and HbA1c with endpoint events. The mediating effect of pulmonary hemodynamics was evaluated to investigate the potential mechanism between hyperglycemia and clinical outcomes. Results During a mean follow-up period of 3.8 years, 219 (35.0%) patients experienced all-cause death or clinical worsening events. Hyperglycemia indices correlated with well-validated variables that reflected the severity of IPAH, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide levels. Multivariable Cox regression analyses indicated that SHR (hazard ratio [HR] 1.328, 95% confidence intervals [CI]: 1.185, 1.489 per 0.1-unit increment, P

Abstract Background With the ongoing prevalence of the emerging variant and global vaccination efforts, the optimal surgical timing for patients with resectable lung cancer in the Omicron-dominant period requires further investigation. Methods This prospective multicenter study involved patients who underwent radical surgery for lung cancer between January 29, 2023 and March 31, 2023. Patients were categorized into four groups based on the interval between SARS-CoV-2 infection and surgery. The main outcomes evaluated were 30-day mortality and 30-day morbidity. Results A total of 2081 patients were enrolled in the study, of which 1837 patients (88.3%) had a confirmed SARS-CoV-2 diagnosis before surgery. Notably, no instances of 30-day mortality were observed in any patient. Patients without prior infection had a 30-day morbidity rate of 15.2%, with postoperative pneumonia occurring in 7.0% of cases. In contrast, patients diagnosed with SARS-CoV-2 before surgery had significantly higher rates of 30-day morbidity and postoperative pneumonia when surgery was performed within 4–5 weeks (adjusted odds ratio (aOR) (95% CI):2.18 (1.29–3.71) and 2.39 (1.21–4.79), respectively) or within 6–7 weeks (aOR (95% CI):2.07 (1.36–3.20) and 2.10 (1.20–3.85), respectively). Conversely, surgeries performed ≥ 8 weeks after SARS-CoV-2 diagnosis exhibited similar risks of 30-day morbidity and pneumonia compared to those in the no prior infection group (aOR (95% CI):1.13 (0.77–1.70) and 1.12 (0.67–1.99), respectively). Conclusions Thoracic surgery for lung cancer conducted 4–7 weeks after SARS-CoV-2 infection is still associated with an increased risk of 30-day morbidity in the Omicron-dominant period. Therefore, surgeons should carefully assess the individual risks and benefits to formulate an optimal surgical strategy for patients with lung cancer with a history of SARS-CoV-2 infection.

Abstract Background Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. Methods A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. Results During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P

Aims Dilated cardiomyopathy (DCM) is characterized by unilateral or bilateral ventricular enlargement and reduced ventricular systolic function, with or without heart failure. In previous studies, we found that a history of chronic obstructive pulmonary disease (COPD) or chronic bronchitis is a high risk factor for DCM combined with pulmonary hypertension (PH). Therefore, we propose that the comorbidity of COPD or chronic bronchitis will increase the cardiogenic mortality of patients with DCM.Methods Data were collected from patients with DCM who were admitted to The First Affiliated Hospital of Guangzhou University of Chinese Medicine from October 2008 to April 2020. The primary endpoint was cardiac death. Multivariable Cox regression analyses were employed to assess the associations between the comorbidities COPD or chronic bronchitis with the study endpoints. Different adjusting models were used to adjust for potential confounders.Results A total of 305 DCM patients were ultimately enrolled, among whom 46 patients had COPD or chronic bronchitis. The median follow-up was 50 months. The rate of cardiac death in the COPD or chronic bronchitis group was significantly greater than that in the non-COPD or nonchronic bronchitis group (p

Abstract The mechanism of hypoxia in chemoresistance of pancreatic ductal adenocarcinoma (PDAC) remains elusive. In this study, we revealed the essential role of miR-485-3p in PDAC, particularly its impact on cancer stemness and gemcitabine resistance under hypoxic conditions. We found substantial downregulation of miR-485-3p in PDAC tissues, with lower expression correlating to poor patient outcomes. Mechanistically, miR-485-3p influenced stemness characteristics, as evidenced by reduced tumor-sphere formation and increased sensitivity to gemcitabine upon overexpression. Moreover, we identified SOX9 and SLC7A11 as two targets of miR-485-3p, which play a vital role in stemness and ferroptosis. Under the hypoxic condition, DNMT3B expression was upregulated, leading to hypermethylation of the miR-485-3p promoter region. The reduced miR-485-3p expression promoted stemness and chemoresistance of PDAC. In conclusion, our findings elucidate the intricate interplay of hypoxia, epigenetic modifications, and ferroptosis in PDAC and shed light on potential avenues for targeted interventions that modulate cancer stemness and chemosensitivity, offering prospects for improved therapeutic strategies for PDAC.

Abstract Background Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. Methods A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. Results During a mean of 3.6 years’ follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P

Objective Hip fracture and falls are significant health concerns. Handgrip strength (HGS) is closely associated with overall muscle strength and physical health. However, the longitudinal relationship between HGS and the risk of hip fractures and falls remains unclear, particularly regarding gender differences. This longitudinal study aimed to investigate the association between HGS and the risk of hip fracture and falls in individuals aged 45 years and above, considering gender‐specific differences over a 4‐year period. Methods This study included 10,092 participants (4471 men and 5621 women) aged 45 years and above from the China Health and Retirement Longitudinal Study (CHARLS). Incidents of hip fractures and falls were recorded during a 4‐year follow‐up, along with various demographic and clinical factors. Participants were categorized into five groups based on their HGS quintiles. Logistic regression models were employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationship between HGS and hip fracture/fall risk. Results During the 4‐year follow‐up period, 223 cases of hip fracture (2.2%) and 1831 cases of falls (18.1%) were documented. Notably, higher HGS demonstrated a strong inverse association with the risk of hip fracture in both males and females (p

Abstract Background Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. Methods Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. Results Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100–4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019–2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358–0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245–0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367–0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231–0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. Conclusions Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Abstract Aims Despite refinements in balloon pulmonary angioplasty (BPA), total occlusion remains a challenge in chronic thromboembolic pulmonary hypertension (CTEPH). Owing to their low success and high complication rates, most interventional cardiologists are reluctant to address total occlusion, and there is a paucity of literature on BPA performance in total occlusion. We aimed to classify total occlusion according to morphology and present an illustrative approach for devising a tailored treatment strategy for each distinct type of total occlusion. Methods and results All patients diagnosed with CTEPH who underwent BPA between May 2018 and May 2022 at Fuwai Hospital in Beijing, China, were included retrospectively. A total of 204 patients with CTEPH who underwent BPA were included in this study. Among these, 38 occluded lesions were addressed in 33 patients. Based on the morphology, we categorized the lesions into three groups: pointed‐head, round‐head, and orifice occlusions. Pointed‐head occlusion could be successfully addressed using soft‐tip wire, round‐head occlusion warranted hard‐tip wire and stronger backup, and orifice occlusion warranted the strongest backup force. The success rates for each group were as follows: pointed‐head (95.45%), round‐head (46.15%), and orifice occlusion (33.33%), with orifice occlusion having the highest complication rate (50%). The classification of occlusion was associated with BPA success (round‐head occlusion vs. pointed‐head occlusion, OR 24.500, 95% CI 2.498–240.318, P = 0.006; orifice occlusion vs. pointed‐head occlusion, OR 42.000, 95% CI 3.034–581.434, P = 0.005). Conclusions Occlusion morphology has a significant impact on BPA success and complication rates. A treatment strategy tailored to each specific occlusive lesion, as outlined in the present study, has the potential to serve as a valuable guide for clinical practitioners.

Hypoxic-ischemic (HI) can cause neonatal brain damage leading to disability. Patients with HI experience long-term neurological issues impacting quality of life. Limited clinical treatments are available despite extensive research on HI's molecular mechanisms. Genistein-3′-sodium sulfonate (GSS), a phytoestrogen, has been found to improve acute brain injury in neonatal rats caused by hypoxic-ischemia, but its potential for chronic stage neurological recovery in HI is unknown. HI neonatal rats were treated with 1 mg/kg GSS once a day for 21 days. Then, a series of behavioral experiments was performed to evaluate the learning, memory, cognition, anxiety level and depression-like behaviors of the rats. GSS treatment reduced neuronal loss, enhanced learning, memory and cognitive function while also alleviated anxiety and depression-like behaviors in HI rats during the recovery period. These findings indicated that GSS exerted enhance neurological function in HI rats during the chronic stage, prompting further research on how it works to potentially develop new therapies.

Acinic cell carcinoma (ACC) is a malignant epithelial salivary gland neoplasm that most frequently occurs in the salivary glands. However, primary ACC of the lung is extremely rare. Due to its low incidence and the lack of related literature, clinicians lack relevant knowledge. It is prone to misdiagnosis, which delays the treatment of patients. Thus, we report a case of primary ACC of the lung confirmed via surgery and pathology, together with a review of relevant literature, in order to summarize the CT imaging manifestations and the value of CT in the diagnosis and treatment of this disease. The aim of this case report was to improve the understanding of primary ACC of the lung and to improve the diagnostic abilities.

BackgroundChildren with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance.MethodsAll children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups.ResultsA total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p

Objective: To explore the mulyi-slice computed tomograpy (MSCT) imaging characteristics of pulmonary mucosa-associated lymphoma tissue. Methods: The clinical data and MSCT findings of eight cases of pulmonary MALT lymphoma confirmed by pathology in our hospital from February 2014 to July 2022 were analyzed retrospectively. The causes of misdiagnosis were also analyzed. Results: Five patients underwent plain and enhanced chest CT scans, and three underwent plain chest CT scans alone. Among the eight patients, four had a single focus, four had multiple foci, and seven showed large patches of high-density shadows. All patients showed air bronchogram, and one showed mixed density patches. CT enhancement showed moderate enhancement in four cases, slight enhancement in one case, and angiography sign in four cases. Conclusion: Primary MALT lymphoma of the lung is an inert tumor with low-grade malignancy. The MSCT findings have certain characteristics. Therefore, it is necessary to obtain diseased tissues in time for pathological examination and immunohistochemistry to make a clear diagnosis.

Abstract Background Cystatin C is a novel biomarker to identify renal dysfunction and cardiovascular risk. Objective The aim of this study was to investigate the role of cystatin C in non-invasive risk prediction in a large cohort of patients with pre-capillary pulmonary hypertension (PH). Method We retrospectively analyzed pre-capillary PH patients with available cystatin C and hemodynamic data derived from right heart catheterization. Results A total of 398 consecutive patients with confirmed pre-capillary PH were recruited from Fuwai Hospital between November 2020 and November 2021. Over a median duration of 282 days, 72 (18.1%) of these patients experienced clinical worsening. Cystatin C levels significantly correlated with cardiac index (r = -0.286, P

Abstract Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014–2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163–3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001–1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well‐validated PH biomarkers, CA125 was still of prognostic value in the low‐risk patients (HR: 1.014, 95% CI: 1.004–1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.

BackgroundThis investigation aimed to examine the epidemiological characteristics of children with liver disease hospitalized for the first time between June 2012 and May 2022 in a tertiary hospital.MethodsThe study retrospectively recruited children aged between 29 days and 18 years who had been hospitalized for liver disease. Clinical characteristics were categorized by age and etiology, and time trends were assessed using linear regression analysis.ResultsA total of 4,313 children were recruited, with a median age of 0.7 (0.2–4.5) years, and 54.5% of the cases were in the 0–1 years age group. Infection was the primary cause of liver disease (30.0%), followed by undiagnosed cases (25.8%), biliary obstructive disease (15.9%), inherited metabolic liver disease (13.9%), and non-alcoholic fatty liver disease (NAFLD) (3.2%). Genetic diagnoses were established in 43.9% (478/1,088) of patients. The percentage of NAFLD demonstrated an upward trend from 1.2% in 2012 to 12.6% in 2022 (p = 0.006). In contrast, the percentage of cytomegalovirus hepatitis decreased from 13.3% in 2012 to 3.4% in 2022 (p = 0.002).ConclusionsLiver disease in infancy makes up the largest group in pediatric liver disease. Infection remains the leading cause of pediatric liver disease. Hospital admissions for NAFLD in children have increased rapidly over the past decade, while cytomegalovirus hepatitis has declined markedly.

Background: Balloon pulmonary angioplasty (BPA) is typically performed in a sequential manner. Objectives: This study aimed to determine the lowest frequency of BPA for patients who could not reach treatment goals in a short period. Design: Retrospective cohort. Methods: We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of performed BPA sessions or treated pulmonary vessels or the ratio of the number of treated pulmonary vessels/the number of baseline lesions (T/P) prior to the initial occurrence of clinical outcome or censored date, we divided patients into different groups. The principal outcome was clinical worsening. Results: After stratifying patients by the number of performed BPA sessions, most baseline parameters were comparable among groups. During follow-up, 31 (16.7%) of 186 patients experienced clinical worsening. The 6-month cumulative clinical worsening-free survival rates of ⩾2 performed sessions group were significantly higher than that of 1 performed session group. The 12-month cumulative rates of clinical worsening-free survival exhibited a declining pattern in the subsequent sequence: ⩾3, 2, and 1 performed BPA sessions, and this trend persisted when follow-up time exceeded 12 months. The 6-, 12-, and 24-month cumulative clinical worsening-free survival rates were comparable between patients with 3 and ⩾4 performed BPA sessions. Similar results were also observed when stratifying patients by the accumulative number of treated pulmonary vessels (⩽8, 9–16, ⩾17) and T/P (⩽0.789, 0.790–1.263, ⩾1.264). Conclusion: To achieve optimal short-term outcomes, patients might need to undergo ⩾2 BPA sessions or have ⩾9 pulmonary vessels treated or have T/P ⩾0.790 within 6 months, and undergo ⩾3 BPA sessions or have ⩾17 pulmonary vessels treated or have T/P ⩾1.264 within 12 months.

The thermal properties of bipolar plates, being key elements of polymer electrolyte membrane fuel cells, significantly affect their heat conduction and management. This study employed an innovative approach known as a heat flow loop integral method to experimentally assess the in-plane thermal conductivity of graphite bipolar plates, addressing the constraints of traditional methods that have strict demands for thermal stimulation, boundary or initial conditions, and sample size. This method employs infrared thermal imaging to gather information from the surface temperature field of the sample, which is induced by laser stimulation. An enclosed test loop on the infrared image of the sample’s surface, situated between the heat source and the sample’s boundary, is utilized to calculate the in-plane heat flow density by integrating the temperature at the sampling locations on the loop and the in-plane thermal conductivity can be determined based on Fourier’s law of heat conduction. The numerical simulation analysis of the graphite models and the experimental tests with aluminum have confirmed the precision and practicality of this method. The results of 1060 aluminum and 6061 aluminum samples, each 1 and 2 mm in thickness, show a deviation between the reference and actual measurements of the in-plane thermal conductivity within 4.3% and repeatability within 2.7%. Using the loop integral method, the in-plane thermal conductivities of three graphite bipolar plates with thicknesses of 0.5 mm, 1 mm, and 1.5 mm were tested, resulting in 311.98 W(m·K)−1, 314.41 W(m·K)−1, and 323.48 W(m·K)−1, with repeatabilities of 0.9%, 3.0%, and 2.0%, respectively. A comparison with the reference value from the simulation model for graphite bipolar plates with the same thickness showed a deviation of 4.7%. The test results for three different thicknesses of graphite bipolar plates show a repeatability of 2.6%, indicating the high consistency and reliability of this measurement method. Consequently, as a supplement to existing technology, this method can achieve a rapid and nondestructive measurement of materials such as graphite bipolar plates’ in-plane thermal conductivity.

Abstract Aims The prognosis is poor for patients with pulmonary artery stenosis‐associated pulmonary hypertension (PAS‐PH). Identifying predictors of prognosis in PAS‐PH is crucial to preventing premature death, which has rarely been investigated. We aimed to explore the cardiopulmonary exercise testing (CPET) parameters to predict the prognosis of these patients. Methods We prospectively included all patients with PAS‐PH who underwent CPET between September 2014 and June 2021 in Fuwai Hospital (ClinicalTrials.gov ID: NCT02061787). The primary outcome was clinical worsening, including death, rehospitalization for heart failure, or deterioration of PH. Results Seventy‐two patients were included in this study. A median of 2‐year follow‐up revealed that 18 (25%) patients experienced clinical worsening. The 1‐year, 3‐year, and 5‐year event‐free survival rates were 92.5%, 81.7%, and 62.7%, respectively. Patients with clinical worsening demonstrated significantly worse baseline haemodynamics and poorer exercise capacity than their counterparts. Multivariable Cox regression identified that peak O2 pulse could independently predict clinical worsening [hazard ratio: 0.344, 95% confidence interval (CI) 0.188–0.631, P

Abstract Background Activated microglia play a key role in initiating the inflammatory cascade following ischemic stroke and exert proinflammatory or anti-inflammatory effects, depending on whether they are polarized toward the M1 or M2 phenotype. The present study investigated the regulatory effect of icaritin (ICT) on microglial polarization in rats after cerebral ischemia/reperfusion injury (CI/RI) and explored the possible anti-inflammatory mechanisms of ICT. Methods A rat model of transient middle cerebral artery occlusion (tMCAO) was established. Following treatment with ICT, a G protein-coupled estrogen receptor (GPER) inhibitor or an extracellular signal-regulated kinase (ERK) inhibitor, the Garcia scale and rotarod test were used to assess neurological and locomotor function. 2,3,5-Triphenyltetrazolium chloride (TTC) and Fluoro-Jade C (FJC) staining were used to evaluate the infarct volume and neuronal death. The levels of inflammatory factors in the ischemic penumbra were evaluated using enzyme-linked immunosorbent assays (ELISAs). In addition, western blotting, immunofluorescence staining and quantitative PCR (qPCR) were performed to measure the expression levels of markers of different microglial phenotypes and proteins related to the GPER–ERK–nuclear factor kappa B (NF-κB) signaling pathway. Results ICT treatment significantly decreased the cerebral infarct volume, brain water content and fluorescence intensity of FJC; improved the Garcia score; increased the latency to fall and rotation speed in the rotarod test; decreased the levels of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), Iba1, CD40, CD68 and p-P65-NF-κB; and increased the levels of CD206 and p-ERK. U0126 (an inhibitor of ERK) and G15 (a selective antagonist of GPER) antagonized these effects. Conclusions These findings indicate that ICT plays roles in inhibiting the inflammatory response and achieving neuroprotection by regulating GPER–ERK–NF-κB signaling and then inhibiting microglial activation and M1 polarization while promoting M2 polarization, which provides a new therapeutic for against cerebral ischemic stroke. Graphical Abstract

Abstract Background The COMPERA 2.0 4-stratum (4-S) risk score has been demonstrated superior over the 3-stratum (3-S) one in patients with pulmonary arterial hypertension and medically managed patients with chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to determine the prognostic value of the original 4-S and 3-S COMPERA 2.0 risk score and two new derivative versions in CTEPH patients who underwent balloon pulmonary angioplasty (BPA). Methods We retrospectively enrolled 175 BPA-treated patients with CTEPH. We assessed the risk stratification before and after each BPA session of CTEPH patients by the original 4-S and 3-S COMPERA 2.0 risk score (by rounding decimal to the nearest integer) and two new proposed derivative versions: the modified version (by rounding decimal to the next integer) and a hybrid version that fuses the original and modified versions. The primary endpoint was clinical worsening events. The secondary outcomes were achieving low-risk profile and mean pulmonary arterial pressure (mPAP)

Abstract Background Ventilatory power is a novel index which could reflect both ventilation efficiency and peripheral blood flow. However, its clinical value in pulmonary hypertension (PH) is rarely discussed. In the present study, we aimed to investigate the diagnostic and prognostic value of ventilatory power as well as its association with disease severity in PH. Methods Consecutive patients with normal hemodynamics and patients diagnosed with PH between September, 2012 and December, 2020 in Fuwai hospital were enrolled. Receiver operating characteristic curves were constructed to determine diagnostic power of ventilatory power and tricuspid regurgitation velocity (TRV). Spearman correlation coefficients were used to evaluate bivariate correlation. Multivariable Cox analysis were used to evaluate the association between ventilatory power and clinical worsening. Results A total of 679 patients were included in the study, among whom 177 were patients with normal hemodynamics, and 502 were patients with PH. Among patients with PH, those experiencing clinical worsening had lower ventilatory power than those did not. The area under the curve of TRV plus ventilatory power was higher than TRV used alone when identifying overt and borderline PH. Ventilatory power was also correlated with well-validated variables that reflected severity of PH, such as NT-proBNP. Multivariable Cox analysis showed that ventilatory power could independently predict clinical worsening and could improve the predictive power of the current PH risk assessment tool. Conclusion Ventilatory power could improve the predictive power of TRV in identifying overt PH and borderline PH. Moreover, it could reflect disease severity and independently predict clinical worsening.

In recent years, more and more researchers are devoting themselves to the studies about authentication based on biomarkers. Among a wide variety of biomarkers, code-modulated visual evoked potential (c-VEP) has attracted increasing attention due to its significant role in the field of brain-computer interface. In this study, we designed a mild-burdened cognitive task (MBCT), which can check whether participants focus their attention on the visual stimuli that evoke c-VEP. Furthermore, we investigated the authentication based on the c-VEP evoked in the cognitive task by introducing a deep learning method. Seventeen participants were recruited to take part in the MBCT experiments including two sessions, which were carried out on two different days. The c-VEP signals from the first session were extracted to train the authentication deep models. The c-VEP data of the second session were used to verify the models. It achieved a desirable performance, with the average accuracy and F1 score, respectively, of 0.92 and 0.89. These results show that c-VEP carries individual discriminative characteristics and it is feasible to develop a practical authentication system based on c-VEP.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors. In addition to behavioral interventions and psychotherapies, and pharmacological interventions, in-depth studies of intestinal microbiota in ASD has obvious abnormalities which may effectively influenced in ASD. Several attempts have been made to indicate that microbiota can reduce the occurrence of ASD effectively. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient’s gastrointestinal tract to improve the gut microenvironment. In this case report, we describe a case of child ASD treated by FMT. The patient have poor response to long-term behavioral interventions. After five rounds of FMT, clinical core symptoms of ASD and gastrointestinal(GI) symptoms were significantly altered. Moreover, the multiple levels of functional development of child were also significantly ameliorated. We found that FMT changed the composition of the intestinal microbiota as well as the metabolites, intestinal inflammatory manifestations, and these changes were consistent with the patient’s symptoms. This report suggests further FMT studies in ASD could be worth pursuing, and more studies are needed to validate the effectiveness of FMT in ASD and its mechanisms.

Abstract Background Excessive inflammatory response is the primary cause of early death in patients with endotoxemia. Interleukin 22 (IL-22) has been shown to play critical roles in the modulation of infectious diseases, but its function in regulating immune responses during endotoxemia remains unclear. Methods Lipopolysaccharide (LPS) was used to induce endotoxemia mouse model with or without a recombinant fusion protein containing human IL-22 (F-652). IL-6, TNF-α, IL-1β, and MCP-1 were measured by ELISA assays. The type of macrophage was assessed by flow cytometry. Real-time PCR was used to detect the expression of S100A9. Results We found that F-652 injection significantly improved the survival rates and reduced pro-inflammatory cytokines (IL-6, TNF-a, IL-1β, MCP-1) in LPS-induced endotoxemia mice. However, the mice injected with F-652 had a higher number of infiltrated immune cells after LPS treatment, suggesting an impaired immune response. Flow cytometry analysis showed a higher number of F4/80+Ly6GhiLy6Chi cells that highly expressed M2-like macrophage markers (Ym1, Arg, CCL17) in the peritoneal cavity of the F-652-treated endotoxemia mice. Further investigation found that these suppressive M2 macrophages might be induced by F-652 since the F-652 treatment could increase S100A9 in vitro. Conclusions Our study suggests that IL-22 has a protective role against endotoxemia by inducing the development of immunosuppressive cells through S100A9.

Extreme weather is frequent and aggressive, posing a huge challenge to urban management capacity. The construction of urban resilience is a systematic project of multi-system coordination. Previous studies have focused on temporal evolution, external system coupling and coordination, and less on the internal study of urban resilience systems. Based on the perspective of the Wuli-Shili-Renli methodology, the study combines urban resilience with Eastern management philosophy. Using a coupled coordination model, the evolutionary laws of key elements of multiple processes in the complex urban resilience system of Henan Province are studied. The coupled coordination mechanism of multiple elements and processes in the province is revealed. It is found that (1) the development of the urban resilient system in Henan Province has gone through two stages from fluctuation to stability. From 2010 to 2015 called “fluctuating growth” and from 2016 to 2019 called “linear growth”. (2) There are three different periods of development for the coordination of the urban resilient system in Henan. Stage 1 (2010–2015) the “coupling teething period”, stage 2 (2016–2017) the “decoupling accumulation period” and stage 3 (2018–2019) the “self-organized explosive period”. (3) Henan has strong preventive power, but weak resistance and recovery power. Then, from the perspective of WSR, the optimal regulation of the regional urban resilient system is proposed.

Abstract Background Local anesthesia has been recommended for percutaneous endoscopic lumbar discectomy (PELD) in recent years; however, the efficacy, including oxidative stress, inflammatory reactions and ventilation effects, when intravenous dexmedetomidine (DEX) is administered during PELD has not been described. Methods Sixty adult patients undergoing PELD were randomly allocated to either an intravenous DEX sedation group (Group A) or a normal saline group (Group B). Respiratory data, including minute ventilation (MV), tidal volume (TV), and respiratory rate (RR), were recorded using a respiratory volume monitor (RVM), and peripheral oxygen saturation (SpO2) was monitored by pulse oximetry. The visual analog score (VAS) was used to assess the level of pain. The serum levels of inflammatory biomarkers including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were to assess inflammatory reactions. The serum levels of oxidative stress biomarkers including malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were also recorded to evaluate oxidative stress. Results There were no significant differences in RR, MV, TV and SpO2 between the two groups at any time point (P > 0.05). Group B exhibited lower serum levels of GSH-PX (P

BackgroundNeonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a common clinical phenotype of citrin deficiency in infants. Its phenotype is atypical, so genetic testing is quite necessary for the diagnosis.Case presentationWe report 4 patients with jaundice and low body weight. Furthermore, the biochemical examination of all showed abnormal liver function and metabolic changes. DNA samples of the patients were extracted and subjected to genetic screening. All candidate pathogenic variants were validated by Sanger sequencing, and CNVs were ascertained by qPCR. The genetic screening revealed 6 variants in 4 patients, and all patients carried compound heterozygous variants of SLC25A13. Importantly, 3 variants were newly discovered: a nonsense mutation in exon17 (c.1803C > G), a frameshift mutation in exon 11(c.1141delG) and a deletion of the whole exon11. Thus, four NICCD patients were clearly caused by variants of SLC25A13. Biochemical indicators of all patients gradually returned to normal after dietary adjustment.ConclusionsOur study clarified the genetic etiology of the four infants, expanded the variant spectrum of SLC25A13, and provided a basis for genetic counseling of the family. Early diagnosis and intervention should be given to patients with NICCD.

Introduction: Guillain-Barré syndrome (GBS) is an autoimmune disorder targeting the peripheral nervous system. The neutrophil-to-lymphocyte ratio (NLR), a simple indicator of immune function, is potentially related to its incidence and severity; however, this should be confirmed. We aimed to evaluate the role of NLR in the diagnosis, severity, and prognosis of GBS. Methods: Data of GBS patients and controls visiting our hospital from January 2010 to December 2020 were retrospectively analyzed (Clinical trial registration: ChiCTR2100053540). Risk factors were determined through logistic regression. Smoothing curves, receiver-operating characteristic curves, and forest plots were drawn. Results: We included 136 GBS patients and 211 controls. NLR, as a continuous variable, was associated with GBS risk (OR, 2.32; 95% CI, 1.68–3.21; p

IntroductionRepair and regeneration of the peripheral nerve are important for the treatment of peripheral nerve injury (PNI) caused by mechanical tears, external compression injuries and traction injuries. Pharmacological treatment can promote the proliferation of fibroblasts and Schwann cells (SCs), which longitudinally fill the endoneurial canal and form Bungner’s band, helping the repair of peripheral nerves. Therefore, the development of new drugs for the treatment of PNI has become a top priority in recent years.MethodsHere, we report that small extracellular vesicles (sEVs) produced from umbilical cord mesenchymal stem cells (MSC-sEVs) cultured under hypoxia promote repair and regeneration of the peripheral nerve in PNI and may be a new therapeutic drug candidate.ResultsThe results showed that the amount of secreted sEVs was significantly increased in UC-MSCs compared with control cells after 48 h of culture at 3% oxygen partial pressure in a serum-free culture system. The identified MSC-sEVs could be taken up by SCs in vitro, promoting the growth and migration of SCs. In a spared nerve injury (SNI) mouse model, MSC-sEVs accelerated the recruitment of SCs at the site of PNI and promoted peripheral nerve repair and regeneration. Notably, repair and regeneration in the SNI mouse model were enhanced by treatment with hypoxic cultured UC-MSC-derived sEVs.DiscussionTherefore, we conclude that hypoxic cultured UC-MSC-derived sEVs may be a promising candidate drug for repair and regeneration in PNI.

BackgroundMost studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn’s disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children.MethodsWe retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy.ResultsTwenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 ± 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029).ConclusionThis study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.

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Background: To achieve favorable hemodynamics, the number of balloon pulmonary angioplasty (BPA) sessions varied significantly among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Increased BPA sessions burdened patients financially and psychologically. We aim to identify baseline characteristics that could predict early BPA response. Methods: Consecutive patients who were diagnosed with inoperable CTEPH and received BPA between May 2018 and October 2021 at Fuwai Hospital were retrospectively collected. Patients were categorized into ‘Early BPA responders’ or ‘Non-early BPA responders’ according to the hemodynamic outcome within the first three BPA sessions. Results: In total, 101 patients were included into analysis. At baseline, non-early BPA responders had lower female proportion, longer disease duration, and poorer laboratory test results compared with early responders, whereas hemodynamics were comparable. After the first three BPA sessions, hemodynamic improvement was more significant in early responders. Incidence of complication was comparable between the two groups. Multivariable logistic analysis identified that female sex (odds ratio [OR]: 7.155, 95% confidence interval [CI]: 1.323-38.692, p = 0.022), disease duration (OR: 0.851, 95% CI: 0.727-0.995, p = 0.043), baseline total bilirubin (OR: 0.934, 95% CI: 0.875-0.996, p = 0.038), and baseline NT-proBNP (OR: 0.473, 95% CI: 0.255-0.879, p = 0.018) were independently associated with early BPA response. Combination of these four parameters could predict 90% early BPA response. Conclusions: Patients with shorter disease duration, female sex, lower baseline NT-proBNP, and lower baseline total bilirubin are more likely to achieve early hemodynamic response to BPA. Moreover, early hemodynamic response was not accompanied with increased incidence of procedure-related complications.

Spinal cord injury (SCI) is a devastating central nervous system disease, caused by physical traumas. With the characteristic of high disability rate, catastrophic dysfunction, and enormous burden on the patient’s family, SCI has become a tough neurological problem without efficient treatments. Contemporarily, the pathophysiology of SCI comprises complicated and underlying mechanisms, in which oxidative stress (OS) may play a critical role in contributing to a cascade of secondary injuries. OS substantively leads to ion imbalance, lipid peroxidation, inflammatory cell infiltration, mitochondrial disorder, and neuronal dysfunction. Hence, seeking the therapeutic intervention of alleviating OS and appropriate antioxidants is an essential clinical strategy. Previous studies have reported that traditional Chinese medicine (TCM) has antioxidant, anti-inflammatory, antiapoptotic and neuroprotective effects on alleviating SCI. Notably, the antioxidant effects of some metabolites and compounds of TCM have obtained numerous verifications, suggesting a potential therapeutic strategy for SCI. This review aims at investigating the mechanisms of OS in SCI and highlighting some TCM with antioxidant capacity used in the treatment of SCI.

Dioscorea cirrhosa is a plant that is used as a dye as well as in medicine. Many metabolites with pharmacological activity exist in the tubers of D. cirrhosa. However, little is known about the mechanism regulating biosynthesis in these metabolites. In this study, transcriptome and metabolome profiling were performed in four color tubers. A total of 531 metabolites, including 62 flavonoids, were identified. Epicatechin and proanthocyanin B2 were the key metabolites that exhibited high content levels in the four tubers. These metabolites were divided into nine classes with distinct change patterns. A total of 22,865 differentially expressed genes (DEGs) were identified by transcriptome analysis. Among these DEGs, we identified 67 candidate genes related to the flavonoid biosynthesis pathway and three genes that played pivotal roles in proanthocyanin (PA) synthesis. A weighted gene co-expression network analysis (WGCNA) revealed that the two modules, “MEblue” and “MEblack,” were two key gene sets strongly associated with phenylpropanoid and flavonoid biosynthesis. We also found that the plant hormone signal transduction biological process exhibited activity in the late stage of tuber color formation. Additionally, we identified 37 hub transcript factors related to flavonoid biosynthesis, of which 24 were found to be highly associated with flavonoid pathway genes. In addition to the MYB-bHLH-WD40 (MBW) genes, we found that the plant hormone gene families exhibited high expression levels. This study provides a reference for understanding the synthesis of D. cirrhosa tuber metabolites at the molecular level and provides a foundation for the further development of D. cirrhosa related plant pigments as well as its further use in the pharmaceutical industry.

Abstract Au nanoparticles synthesized from colloidal techniques have the capability in many applications such as catalysis and sensing. Au nanoparticles function as both catalyst and highly sensitive SERS probe can be employed for sustainable and green catalytic process. However, capping ligands that are necessary to stabilize nanoparticles during synthesis are negative for catalytic activity. In this work, a simple effective mild thermal treatment to remove capping ligands meanwhile preserving the high SERS sensitivity of Au nanoparticles is reported. We show that under the optimal treatment conditions (250 °C for 2 h), 50 nm Au nanoparticles surfaces are free from any capping molecules. The catalytic activity of treated Au nanoparticles is studied through H2O2 decomposition, which proves that the treatment is favorable for catalytic performance improvement. A reaction intermediate during H2O2 decomposition is observed and identified.

Aims: Impairment of right ventricle-to-pulmonary artery coupling (RV-PA coupling) is a major determinant of poor prognosis in patients with pulmonary hypertension. This study sought to evaluate the ability of an echo-derived metric of RV-PA coupling, the ratio between tricuspid annular plane systolic excursion (TAPSE), and pulmonary artery systolic pressure (PASP) and to predict adverse clinical outcomes in chronic thromboembolic pulmonary hypertension (CTEPH). Methods and results: A total of 205 consecutive patients with confirmed CTEPH were retrospectively recruited from Fuwai Hospital between February 2016 and November 2020. Baseline echocardiography, right heart catheterization, and cardiopulmonary exercise testing were analyzed. Patients with lower TAPSE/PASP had a significantly compromised echocardiographic and hemodynamic status and exercise capacity at baseline. The TAPSE/PASP ratio correlated significantly with hemodynamic parameters, including pulmonary vascular resistance ( r = −0.48, p

BackgroundLittle is known regarding the quantification of sleep apnea- and hypoxemia-elicited heart rate (HR) response and its prognostic significance of the cardiovascular risk. We sought to explore the impact of HR response and variability specific to obstructive sleep apnea (OSA) on the occurrence of a common cardiovascular event – acute myocardial infarction (AMI).MethodsConsecutive patients with suspected OSA were enrolled and underwent nocturnal respiratory study and electrocardiography monitoring. The minimal oxygen saturation (minSpO2) was determined from the oxygen saturation curve under a subject-specific search window. Primary HR metrics such as maximal HR in response to minSpO2 and respiratory event-specific HR variability were computed from the synchronized recordings. Multivariate regression analyses were conducted to analyze the associations between individualized HR metrics and the occurrence of AMI.ResultsOf 2,748 patients recruited, 39% (n = 1,071) had moderate-to-severe OSA (respiratory event index, REI ≥ 15), and 11.4% (n = 313) patients had AMI. Patients with AMI experienced severe OSA, severe minSpO2, and greater HR reactions. Patients with minSpO2 73 bpm) was significantly associated with AMI (OR 1.72, 95% CI: 1.32–2.23, p < 0.001). Patients with both severe minSpO2 (

Niemann–Pick disease is a relatively common lysosomal storage disease. Cholestatic liver disease is a typical clinical phenotype of Niemann–Pick disease in infancy. The diagnosis is traditionally based on Niemann–Pick cells in bone marrow smears or liver biopsies. Treatment for cholestatic liver disease mainly includes ursodeoxycholic acid and liver protection drugs. Here, we reported two cases of Niemann–Pick disease type C, diagnosed by genetic analysis during early infancy. Besides cholestatic jaundice, the two patients also exhibited signs of immune system hyperactivity, such as elevated immunoglobulins or multiple autoantibodies, which might require the application of glucocorticoids. In addition, three novel missense variants of the NPC1 gene were identified. The findings suggest that immune activation should be considered as a “new” clinical phenotype of lysosomal storage diseases.

BackgroundSerum uric acid (UA) has long been identified as a prognostic factor of adverse outcomes in pulmonary hypertension. However, there remains a paucity of evidence on patients with idiopathic pulmonary artery hypertension (IPAH) in the era of targeted drug therapy. This study aims to explore the impact of serum UA levels on the disease severity and mortality in patients with IPAH.MethodsConsecutive patients diagnosed with IPAH were enrolled, from which UA levels at baseline and the first follow-up were collected. Patients were divided into groups of “hyperuricemia,” which is defined as serum UA level ≥357 μmol/L in women and ≥420 μmol/L in men, and otherwise “normouricemia.” The potential relationship between UA and hemodynamics at right heart catheterization was investigated. Associations between UA and survival were evaluated by Kaplan-Meier analysis and Cox proportional hazard modeling.ResultsOf 207 patients with IPAH, 121 (58.5%) had hyperuricemia. Higher serum UA levels were associated with lower cardiac index (r = 0.47, p < 0.001) and higher pulmonary vascular resistance (r = 0.36, p < 0.001). During a median follow-up of 34 months, there were 32 deaths recorded, accounting for a 15.5% mortality rate. Patients with hyperuricemia had a significantly lower survival rate than those with normouricemia (log-rank test, p = 0.002). Hyperuricemia at baseline was independently associated with a 2.6-fold increased risk of 5-year death, which was consistent across different subgroups, especially in females and those aged ≥30 years (each p < 0.05). Individuals with higher variability in UA had a higher mortality than those with stable UA (log-rank test, p = 0.024).ConclusionsBaseline hyperuricemia and high variability in serum UA at first follow-up were related to a higher rate of 5-year mortality in patients with IPAH. Closely detecting the UA levels may aid in the early recognition of IPAH patients at higher mortality risk.

Immune checkpoint inhibitors (ICIs) are widely used to treat local or metastatic lung cancer. However, the efficacy of ICI in patients with brain metastases (BM) from lung cancer is unknown. This study aimed to evaluate the efficacy of PD-1/PD-L1 ICIs compared with chemotherapy for patients with lung cancer with BM. Electronic databases (PubMed, Embase, The Cochrane Library, and Web of Science) were searched. The meta-analysis assessed overall survival (OS) and progression-free survival (PFS) of the PD-1/PD-L1 inhibitors axis and its relationship with pathological type, drug modality, and the treatment line number in patients with BM from lung cancer. We included 694 patients with BM from lung cancer from 11 randomized controlled trials. Statistical analysis showed that compared with chemotherapy, PD-1/PD-L1 inhibitors could significantly prolong OS (hazard ratio HR=0.75, 95%confidence interval 95%CI=0.51–0.99) and PFS (HR=0.65, 95%CI=0.51–0.80). In the subgroup analysis, ICIs plus chemotherapy improved PFS (HR=0.60, 95%CI=0.40–0.80), but not OS (HR=0.75, 95%CI=0.30–1.19). The efficacy of ICI monotherapy in patients with BM was significantly different between OS and PFS: OS pooled HR=0.81 (95%CI=0.57–1.05) and PFS=0.78 (95%CI=0.62–0.94). Among different pathological types, the OS pooled HR was 0.67 (95%CI=0.39–0.95) for non-small cell lung cancer (NSCLC) and 0.94 (95%CI=0.56–1.33) for small cell lung cancer (SCLC); the PFS pooled HR was 0.58 (95%CI=0.39–0.76) for NSCLC and 0.79 (95%CI=0.65–0.93) for SCLC. Subgroups analysis of treatment line showed that no advantage for OS with ICIs as first-line or subsequent-line therapy, whereas ICIs as first-line (HR=0.63, 95%CI=0.53–0.74) and second-line (HR=0.62, 95%CI=0.62–0.96) benefitted PFS. This meta-analysis implied that compared with chemotherapy, PD-1/PD-L1 inhibitors significantly improved efficacy treatment of patients with BM from lung cancer. Further studies are needed to confirm the role of ICIs in different pathological types and drug treatment modalities.

Background: Balloon pulmonary angioplasty (BPA)-related complications are not uncommon and could contribute to perioperative mortality. However, there is a lack of a prediction model for BPA-related complications. Methods: Data from consecutive patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) who underwent BPA were retrospectively analyzed. The primary outcome was BPA-related complications. The secondary outcomes were mortality and hemodynamics after BPA. Results: A total of 207 patients with 614 BPA sessions were included. Complications occurred during 63 sessions (10.26%) in 49 patients. Hemoptysis or hemosputum (6.51%) was the most common complication, whereas pulmonary reperfusion edema was rare (0.49%). Multivariable logistic regression identified that disease duration, mean pulmonary arterial pressure (mPAP) and the proportion of occlusion lesions were correlated with BPA complications. A nomogram was constructed accordingly, which had the highest area under curve (0.703) and was superior to previously reported predictors [nomogram vs. mPAP, net reclassification index (95% confidence interval (CI)), 0.215 (0.002, 0.427), p = 0.047; integrated discrimination index (95% CI), 0.059 (0.010, 0.109), p = 0.018]. The nomogram was found to be accurate based on validation and calibration (slope 0.978, Bier score 0.163). After adjusting for the number of BPA sessions in multivariable linear regression, the occurrence of complications was not associated with hemodynamic improvement after BPA. The 3-year survival was also comparable between patients with and without complications (98.0% vs. 94.8%, log-rank p = 0.503). Conclusions: The nomogram, comprising mPAP, the proportion of occlusion lesions and disease duration, could better predict BPA-related complications than previously reported single parameters. Distinctively, the occurrence of complications did not impair the beneficial impact of BPA on hemodynamics and survival. The occurrence of complications should not discourage patients from continuing BPA sessions.

Purpose: To screen RPE65 in 187 families with Leber congenital amaurosis (LCA). Methods: Sanger sequencing and/or targeted exome sequencing was employed to identify mutations in the RPE65 gene, and intrafamilial cosegregation analysis if DNA was available. In silico analyses and splicing assay were used to evaluate the variants’ pathogenicity. Results: Genetic analysis revealed 15 mutations in RPE65 in 14 pedigrees, including one splice-site mutation, one frameshift mutation, three nonsense mutations, and ten missense mutations. Of the mutations identified in RPE65, seven are novel associated with LCA, including five missense variants (c.124C>T, c.149T>C, c.340A>C, c.425A>G, and c.1399C>G) and two indel (insertions or deletions) variants (c.858+1delG and c.1181_1182insT). In vitro splicing assay was performed to evaluate the functional impact on RNA splicing of novel mutations if two of three in silico analyses were predicated to be non-pathogenic at the protein level. Among these 15 variants, 14 were classified as ‘pathogenic variants,’ and a variant (c.124C>T) was ‘variants with uncertain significance’ according to the standards and guidelines of the American College of Medical Genetics and Genomics. Conclusions: Mutations in RPE65 were responsible for 11 of the cohort of 187 Chinese families with LCA, which expands the spectrum of RPE65-related LCA in the Chinese population and potentially facilitates its clinical implementation.

A digital twin is regarded as a potential solution to optimize positive energy districts (PED). This paper presents a compact review about digital twins for PED from aspects of concepts, working principles, tools/platforms, and applications, in order to address the issues of both how a digital PED twin is made and what tools can be used for a digital PED twin. Four key components of digital PED twin are identified, i.e., a virtual model, sensor network integration, data analytics, and a stakeholder layer. Very few available tools now have full functions for digital PED twin, while most tools either have a focus on industrial applications or are designed for data collection, communication and visualization based on building information models (BIM) or geographical information system (GIS). Several observations gained from successful application are that current digital PED twins can be categorized into three tiers: (1) an enhanced version of BIM model only, (2) semantic platforms for data flow, and (3) big data analysis and feedback operation. Further challenges and opportunities are found in areas of data analysis and semantic interoperability, business models, data security, and management. The outcome of the review is expected to provide useful information for further development of digital PED twins and optimizing its sustainability.

Excitatory toxicity due to excessive glutamate release is considered the core pathophysiological mechanism of cerebral ischemia. It is primarily mediated by N-methyl-D-aspartate receptors (NMDARs) on neuronal membranes. Our previous studies have found that icaritin (ICT) exhibits neuroprotective effects against cerebral ischemia in rats, but the underlying mechanism is unclear. This study aims to investigate the protective effect of ICT on glutamate-induced neuronal injury and uncover its possible molecular mechanism. An excitatory toxicity injury model was created using rat primary cortical neurons treated with glutamate and glycine. The results showed that ICT has neuroprotective effects on glutamate-treated primary cortical neurons by increasing cell viability while reducing the rate of lactate dehydrogenase (LDH) release and reducing apoptosis. Remarkably, ICT rescued the changes in the ERK/DAPK1 signaling pathway after glutamate treatment by increasing the expression levels of p-ERK, p-DAPK1 and t-DAPK1. In addition, ICT also regulates NMDAR function during glutamate-induced injury by decreasing the expression level of the GluN2B subunit and enhancing the expression level of the GluN2A subunit. As cotreatment with the ERK-specific inhibitor U0126 and ICT abolishes the beneficial effects of ITC on the ERK/DAPK1 pathway, NMDAR subtypes and neuronal cell survival, ERK is recognized as a crucial mediator in the protective mechanism of ICT. In conclusion, our findings demonstrate that ICT has a neuroprotective effect on neuronal damage induced by glutamate, and its mechanism may be related to inactivating GluN2B-containing NMDAR through the ERK/DAPK1 pathway. This study provides a new clue for the prevention and treatment of clinical ischemic cerebrovascular diseases.

Aiming at the problem of real-time detection and location of moving objects, the deep learning algorithm is used to detect moving objects in complex situations. In this paper, based on the deep learning algorithm of wireless sensor networks, a novel target motion detection method is proposed. This method uses the deep learning model to extract visual potential representation features through offline similarity function ranking learning and online model incremental update and uses the hierarchical clustering algorithm to achieve target detection and positioning; the low-precision histogram and high-precision histogram cascade the method which determines the correct position of the target and achieves the purpose of detecting the moving target. In order to verify the advantages and disadvantages of the deep learning algorithm compared with traditional moving object detection methods, a large number of comparative experiments are carried out, and the experimental results were analyzed qualitatively and quantitatively from a statistical perspective. The results show that, compared with the traditional methods, the deep learning algorithm based on the wireless sensor network proposed in this paper is more efficient. The detection and positioning method do not produce the error accumulation phenomenon and has significant advantages and robustness. The moving target can be accurately detected with a small computational cost.

Computer technology and related Internet of things technology have penetrated into people’s daily life and industrial production; even in competitive sports training and competition, the Internet of things technology has also been a large number of applications. Traditional intelligent wearable devices are mainly used to calculate the steps of athletes or sports enthusiasts, corresponding physical data, and corresponding body indicators. The energy consumption calculated by these indexes is rough and the corresponding error is large. Based on this, this paper will design a wearable device which can accurately calculate and monitor sports energy consumption based on relevant sensors and Internet of things technology. The corresponding core algorithm is the step counting algorithm, which can accurately calculate the relationship between human motion and the corresponding energy consumption and feed back to the intelligent device. In the experiment, the wearable device designed in this paper is compared with the traditional intelligent device. The experiment shows that the wearable device proposed in this paper is more accurate in energy consumption estimation than the traditional device, and its corresponding energy consumption is relatively small.

The aim of the research was to determine the protective effect and mechanism of Pteris wallichiana J. Agardh extract (PWE) on DSS-induced ulcerative colitis (UC) in mice. In this research, PWE is rich in flavonoids and diterpenoids by UPLC-MS/MS analysis. In LPS-induced RAW264.7 cells, PWE reduced the productions of inflammatory factors (i.e., NO, TNF-α, IL-6, and IL-1β). In DSS-induced UC in mice, PWE improved disease activity index (DAI) score, attenuated oxidative stress by decreasing MPO and MDA activities and activating GSH and SOD levels, and inhibited TNF-α, IL-6, and IL-1β expressions in the colonic tissues. PWE also improved the intestinal barrier by upregulating the expressions of tight junction proteins, including occludin and ZO-1. Moreover, PWE extract alleviated intestinal inflammation by suppressing the TLR4/MyD88/NF-κB signaling pathway. Conclusion: PWE can alleviate DSS-induced UC in mice by increasing the expressions of intestinal tight junction proteins and inhibiting the TLR4/NF-κB inflammatory pathway.