GPR176 Is a Biomarker for Predicting Prognosis and Immune Infiltration in Stomach Adenocarcinoma.

Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment for stomach adenocarcinoma (STAD), but only a minority of patients benefit from it. It is believed that the poor therapeutic efficacy is attributed to the complex tumor immune microenvironment (TIM) of STAD. Therefore, elucidating the specific regulatory mechanism of TIM in STAD is critical. Previous study suggests that GRP176 may be involved in regulating the pace of circadian behavior, and its role in tumors has not been reported. In this study, we first found that GPR176 was highly expressed in STAD and negatively correlated with patient prognosis. Next, we investigated the relationship between GPR176 and clinical characteristics, and the results showed that the stage is closely related to the level of GPR176. In addition, our further analysis found that GRP176 expression level was significantly correlated with chemotherapeutic drug sensitivity and ICI response. KEGG and GO analyses showed that GPR176 might be involved in stromal remodeling of STAD. Furthermore, we analyzed the association between GPR176 expression and immune implication, and the results revealed that GPR176 was negatively related to the infiltration of various immune cells. Interestingly, GPR176 induced the conversion of TIM while reducing the tumor immune burden (TMB). The expression of GRP176 is closely related to the level of various immunomodulators. Moreover, we performed univariate and multivariate regression analyses on the immunomodulators and finally obtained 4 genes (CRCR4, TNSF18, PDCD1, and TGFB1). Then, we constructed a GRP176-related immunomodulator prognostic model (GRIM) based on the above 4 genes, which was validated to have good predictive power. Finally, we developed a nomogram based on the risk score of GRIM and verified its accuracy. These results suggested that GPR176 is closely related to the prognosis and TIM of STAD. GPR176 may be a new potential target for immunotherapy in STAD.

Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs.

BACKGROUND: The associations between vitamin D and coronavirus disease 2019 (COVID-19) infection and clinical outcomes are controversial. The efficacy of vitamin D supplementation in COVID-19 is also not clear. METHODS: We identified relevant cohort studies that assessed the relationship between vitamin D, COVID-19 infection and associated death and randomized controlled trials (RCTs) that reported vitamin D supplementation on the outcomes in patients with COVID-19 by searching the PubMed, EMBASE, and medRxiv databases up to June 5th, 2021. Evidence quality levels and recommendations were assessed using the GRADE system. RESULTS: Eleven cohort studies with 536,105 patients and two RCTs were identified. Vitamin D deficiency (< 20 ng/ml) or insufficiency (< 30 ng/ml) was not associated with an significant increased risk of COVID-19 infection (OR for < 20 ng/ml: 1.61, 95% CI: 0.92-2.80, I2 = 92%) or in-hospital death (OR for < 20 ng/ml: 2.18, 95% CI: 0.91-5.26, I2 = 72%; OR for < 30 ng/ml: 3.07, 95% CI: 0.64-14.78, I2 = 66%). Each 10 ng/ml increase in serum vitamin D was not associated with a significant decreased risk of COVID-19 infection (OR: 0.92, 95% CI: 0.79-1.08, I2 = 98%) or death (OR: 0.65, 95% CI: 0.40-1.06, I2 = 79%). The overall quality of evidence (GRADE) for COVID-19 infection and associated death was very low. Vitamin D supplements did not significantly decrease death (OR: 0.57, I2 = 64%) or ICU admission (OR: 0.14, I2 = 90%) in patients with COVID-19. The level of evidence as qualified using GRADE was low. CONCLUSIONS: Current evidence suggested that vitamin D deficiency or insufficiency was not significantly linked to susceptibility to COVID-19 infection or its associated death. Vitamin D supplements did not significantly improve clinical outcomes in patients with COVID-19. The overall GRADE evidence quality was low, we suggest that vitamin D supplementation was not recommended for patients with COVID-19.

Inhibition of neointimal hyperplasia in rats treated with atorvastatin after carotid artery injury may be mainly associated with down-regulation of survivin and Fas expression.

CONTEXT: Atorvastatin is a member of the drug class known as statins, which is used for lowering blood cholesterol. OBJECTIVE: The present study investigates the effect and mechanism of atorvastatin on neointimal hyperplasia after carotid artery injury (CAI) of rat. MATERIALS AND METHODS: Fifty male rats were randomly divided into four groups: control group, sham-operated group, model group, and atorvastatin treatment group. The treatment group was fed with atorvastatin (10 mg/kg) with gastro-gavage at 5 p.m. every day for 28 d after surgery. The control group, model group, and sham-operated group were fed with the same volume of distilled water instead. The proliferations of intimal and medial layers were evaluated by hematoxylin & eosin (H&E) staining. The apoptosis of vascular smooth muscle cells (VSMCs) was determined by terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) staining. Plasma concentrations of survivin and sFas were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Atorvastatin reduced neointimal formation and increased apoptosis of VSMCs in neointima. VSMCs apoptosis emerged at 3 d (8.42 ± 0.449 µm) and the intimal proliferation peaked by the end of 14 d (41.58 ± 1.64 µm). The plasma levels of survivin and sFas were gradually increased with the neointimal hyperplasia and increasingly decreased after atorvastatin treatment. The plasma levels of survivin and sFas in rats were elevated at 3 d (464.80 ± 105.27 pg/ml and 3256.00 ± 478.20 pg/ml, respectively), reached the peak of survivin at 14 d (1089.20 ± 232.32 pg/ml) and sFas at 7 d (4362.00 ± 639.92 pg/ml) and decreased at 28 d (562.00 ± 90.11 pg/ml and 2148.00 ± 257.14 pg/ml, respectively) in the model group. Compared with the model group, the atorvastatin treatment group has significantly less neointimal hyperplasia and more apoptosis of VSMCs. CONCLUSIONS: Atorvastatin can inhibit neointimal hyperplasia and promote SMCs apoptosis in neointimal layers, which may be mainly associated with down-regulation of survivin and Fas expression after CAI of rat.

[Protein interacting with kinase Cα mediates the down-regulation of myocardial norepinephrine transporter expression in mice with adriamycin-induced congestive heart failure].

OBJECTIVE: To investigate the interaction between myocardial norepinephrine (NET) and protein interacting with kinase Cα (PICK1), and examine the myocardial expression pattern of NET and PICK1 in mice with adriamycin-induced congestive heart failure. METHODS: (1) Cellular experiments: 293T cells were transfected with NET, GFP-PICK1, NET+GFP-PICK1 or NET+GFP-PICK1(KD-AA), respectively. Immunofluorescence staining was performed 48 h after the transfection. (2) Animal experiments: 40 male C57BL/6J mice were divided into control group and adriamycin group (intraperitoneal injection of 2 mg/kg adriamycin with a cumulative amount of 22 mg/kg). The myocardial mRNA and protein expression level of NET, PICK1 and adrenergic receptor (ß1-AR) were detected by real-time PCR and Western blot after 10 weeks. RESULTS: (1) PICK1 mediates the intracellular trafficking of NET. (2) Compared to controls, cardiac mRNA expression of NET remained unchanged, but PICK1 and ß1-AR mRNA level were significantly reduced in the heart failure mice. (3) Myocardial NET protein expression level was significantly reduced, whereas tyrosine hydroxylase (TH) protein expression was significantly upregulated in heart failure mice. (4) The myocardial density of sympathetic nerve fibers remained unchanged in heart failure mice. CONCLUSIONS: Cardiac expression of NET and PICK1 are down-regulated in heart failure mice. Reduced PICK1-mediated intracellular trafficking of NET may be involved in the impairment of NET function in this congestive heart failure mice model.

Early prediction of remaining useful life for lithium-ion batteries based on CEEMDAN-transformer-DNN hybrid model.

A reliable and safe energy storage system utilizing lithium-ion batteries relies on the early prediction of remaining useful life (RUL). Despite this, accurate capacity prediction can be challenging if little historical capacity data is available due to the capacity regeneration and the complexity of capacity degradation over multiple time scales. In this study, data decomposition, transformers, and deep neural networks (DNNs) are combined to develop a model of RUL prediction for lithium-ion batteries. Complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) is used for battery capacity sequential data to account for the capacity regeneration effect. The transformer networks are leveraged to predict each component of capacity regeneration thus improving the model's ability to handle long sequences while reducing the amount of data. The global degradation trend is predicted using a deep neural network. We validated the early prediction performance of the model using two publicly available battery datasets. Results show that the prediction model only uses 25%-30% data to achieve high accuracy. In the two public data sets, the RMSE errors were 0.0208 and 0.0337, respectively. A high level of accuracy is achieved with the model proposed in this study, which is based on fewer capacity data.

Abdominal pain in an adolescent girl with acute phlegmonous gastritis: a case report.

Acute phlegmonous gastritis (APG), a rare clinical condition, is mainly characterized by bacterial invasion in the gastric lining and is associated with a high mortality rate. The symptoms of APG include abdominal pain, nausea, vomiting, fever, and infection. Notably, the lack of specificity in the clinical presentation presents challenges in the early diagnosis of the disease. APG is often prevalent in adults, with a higher incidence in men than women. However, patients of other ages may also be affected. We herein present a case report of a 12-year-old girl who was admitted to the hospital with gastrointestinal symptoms and fever. The patient's imaging findings were compatible with APG. Despite the requirement for surgical treatment in most cases of phlegmonous gastritis, our patient rapidly improved with imaging and antibiotic therapy. This case demonstrates the success of antibiotic therapy with early diagnosis.

Relative Entropy Regularized Sample-Efficient Reinforcement Learning With Continuous Actions.

In this article, a novel reinforcement learning (RL) approach, continuous dynamic policy programming (CDPP), is proposed to tackle the issues of both learning stability and sample efficiency in the current RL methods with continuous actions. The proposed method naturally extends the relative entropy regularization from the value function-based framework to the actor-critic (AC) framework of deep deterministic policy gradient (DDPG) to stabilize the learning process in continuous action space. It tackles the intractable softmax operation over continuous actions in the critic by Monte Carlo estimation and explores the practical advantages of the Mellowmax operator. A Boltzmann sampling policy is proposed to guide the exploration of actor following the relative entropy regularized critic for superior learning capability, exploration efficiency, and robustness. Evaluated by several benchmark and real-robot-based simulation tasks, the proposed method illustrates the positive impact of the relative entropy regularization including efficient exploration behavior and stable policy update in RL with continuous action space and successfully outperforms the related baseline approaches in both sample efficiency and learning stability.

A Self-Crystallized Nanofibrous Ni-GDC Anode by Magnetron Sputtering for Low-Temperature Solid Oxide Fuel Cells.

The optimum composition ratio of the anode cermet (Ni-GDC) for solid oxide fuel cells (SOFCs) varies because the electron-collecting mechanism is different depending on its applications. A Co-sputtering method facilitates ratio control with sputtering power adjustment. However, there is a practical issue with fabricating anode cermet with various ratios attributed to the large sputtering yield gap of the metal target, Ni, and the ceramic target, gadolinia-doped ceria (GDC). Therefore, in this study, a Gd-Ce metal alloy was applied instead of GDC to match the sputtering rate with that of Ni, which enables a wide ratio range achievement. A thin film of Gd-Ce oxidized after deposition and successfully transformed to crystallized GDC under a SOFC operation environment. X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM) confirmed its crystallinity, and the film deposited with various power ratios was sputtered on the ScSZ electrolyte pellet to clarify the optimum Ni-GDC ratio for thin-film SOFCs. Last, the Ni-GDC was applied to anodized aluminum oxide (AAO)-supported SOFCs to maximize the performance. The performance change according to the thickness of Ni-GDC was identified, and the best performance among them was 638 mW/cm2 at 500 °C.

Patent ductus arteriosus shunting direction and diameter predict inpatient outcomes in newborns with congenital diaphragmatic hernia.

Objective: To evaluate whether the patent ductus arteriosus (PDA) can serve as a predictive factor for inpatient outcomes in congenital diaphragmatic hernia (CDH) patients. Methods: A retrospective cohort study was conducted on 59 CDH patients at the Capital Institute of Pediatrics from January 2020 to August 2022. Echocardiography was performed at least three times: within 2-3 h after birth, pre-operatively, and post-operatively of CDH surgery. Based on the direction of the PDA shunt in the first echocardiogram, patients were classified into three groups: left-to-right shunting or closed PDA (L-R), bi-directional shunting, and right-to-left shunting (R-L). Results: The mortality rate was 15.3% (9/59), with all non-survivors having R-L shunting and group mortality of 39.1% (9/23). The direction of the PDA shunt was significantly associated with the duration of ventilation and length of hospital stay (p < 0.05). Decreased PDA diameter or pre-operative shunting direction change towards L-R or bi-directional shunting were associated with higher survival rates, while increased PDA diameter or continuous R-L shunting were associated with higher mortality rates. Pre-operative PDA shunt direction, PDA size after birth and before surgery, gestational age of diagnosis, and shortening fraction before surgery were significantly correlated with patient outcomes. The direction of the preoperative PDA shunt was the most relevant factor among these relationships (p = 0.009, OR 20.6, CI 2.2∼196.1). Conclusion: Our findings highlight the importance of monitoring changes in PDA shunt directionality and diameter in the early stage after birth, as these parameters may serve as valuable predictors of patient outcomes.

Reference values and the Z-score values of tricuspid annular plane systolic excursion in Chinese children.

To establish age-specific and body surface area (BSA)-specific reference values of Tricuspid Annular Plane Systolic Excursion (TAPSE) for children under 15 years old in China. A retrospective study was conducted in Children's Hospital Attached to the Capital Institute of Pediatrics. A total of 702 cases were included in this research to establish reference values of TAPSE in Chinese children. SPSS 25.0 (IBM) was used for data analysis. Lambda-mu-sigma method was used to calculate and construct the age-specific and BSA-specific percentiles and Z-score curves of TAPSE. The mean value of TAPSE increased with age and BSA from 0 to 15 years in a nonlinear way and reached the adult threshold (17 mm) until 1 year old. There was no difference between genders. TAPSE values increased with age and BSA in Chinese children aged between 0 and 15 years and there was no difference between boys and girls. A prospective, multicenter cohort study from different parts of China is supposed to be conducted in the future to reflect the whole spectrum of TAPSE in Chinese children.

Synthesis of BaCO3 nanowires and their humidity sensitive property.

Barium carbonate (BaCO3) nanowires have been synthesized for the first time by using the composite hydroxide mediated (CHM) method. The products are characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). Humidity sensors based on BaCO3 nanowires have been fabricated. The response to humidity in static and dynamic measurement proves the ultrasensitive property of the sensors. The resistance changes from 386 M(omega) to 7.1 M(omega) as the relative humidity (RH) increases from 20% to 95%. The response and recovery time of the resistance is 16 s and 56 s versus the changes of relative humidity from 25% to 85%. These results indicate promising applications of BaCO3 nanowires in a highly sensitive environmental monitoring and humidity control electronic device.

Deciphering the mysteries of crisscross heart by transthoracic echocardiography.

BACKGROUND: Accurate diagnosis of crisscross heart and its associated anomalies is important but problematic for cardiologists. This study aimed at identifying unique transthoracic echocardiographic features and common associated lesions of this complex condition. METHOD: Clinical and echocardiographic features of 10 patients with crisscross anatomy were studied. Echocardiographic findings were verified by cardiac magnetic resonance imaging or surgical inspection. RESULTS: Crisscross anatomy (10 patients, age at diagnosis ranged from 1 month to 25 years, five female) was identified in 0.076% of patients with congenital heart diseases from 1985 to 2006. All patients had cyanosis and 80% of them were underweight. Superior-inferior ventricles (SIV) and crossed ventricular inflow streams were seen in 90% and 100% of patients, respectively. All patients had abnormal ventriculo-arterial (VA) connections: five with transposition of great artery (L-type: n = 2; D-type: n = 3) and five with double outlet right ventricle. Commonly associated anomalies included ventricular septal defects (100%), right ventricular outflow tract obstruction (60%), atrioventricular valves straddling or overriding (50%), atrial septal defect (40%), and right ventricular hypoplasia (30%). Seven patients received cardiac surgery for the relief of cyanosis. CONCLUSIONS: SIV and crossed inflow streams are important diagnostic features for crisscross heart by transthoracic echocardiogram. The hemodynamic consequences of abnormal VA connections and associated defects impact surgical management.

[Retracted] Knockdown of AQP1 inhibits growth and invasion of human ovarian cancer cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Fig. 2B and flow cytometric data shown in Fig. 3B bore unexpected similarities to data appearing in different form in other articles by different authors. Furthermore, there were additional concerns regarding the possibly anomalous appearance of cell migration data shown in Fig. 4B. Owing to the fact that some of the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 5499­5504, 2017; DOI: 10.3892/mmr.2017.7282].

Persistent fifth aortic arch: a single-center experience, case series.

BACKGROUND: Persistent fifth aortic arch (PFAA) is an extremely rare congenital cardiovascular malformation and there is limited data in the literature. The objective of this study is to enhance our understanding and diagnosis of PFAA from echocardiography and computed tomography angiography (CTA) findings, and to evaluate the application of echocardiography in the diagnosis of PFAA. METHODS: We retrospectively reviewed five cases of PFAA diagnosed from October 2016 to September 2019 at the Affiliated Children's Hospital of Capital Institute of Pediatrics. We described their diagnosis by echocardiography and CTA findings, and medical history. RESULTS: Five cases of PFAA were identified in the study. Patients aged from 3 to 48 months and weighed from 4 to 12 kg presented different clinical symptoms upon clinical examination. All the patients completed a primary echocardiographic assessment; however, the first two patients were misdiagnosed by echocardiography and was confirmed by supplemental CTA while the other three patients were directly diagnosed by echocardiography. Surgery was necessary for three patients, two of whom accepted and one refused. The other two patients only needed a follow-up assessment, which showed good results. CONCLUSIONS: The clinical manifestation of PFAA in our patient population was atypical, and their diagnosis depended on the use of echocardiography. In the case of uncertainty, the final diagnosis was confirmed by CTA. Although the nomenclature and embryonic origin of PFAA remains controversial, the accurate diagnosis of aortic arch abnormalities and associated malformations are imperative for time-sensitive treatments.

Saikosaponin a ameliorates lipopolysaccharide and d­galactosamine-induced liver injury via activating LXRα.

Saikosaponin a (SSa), one of the major active components of Bupleurum falcatum, has antioxidant and anti-inflammatory pharmacological properties. However, the effects of SSa on liver injury have not been reported. In the present study, we evaluated the protective effects and mechanisms of SSa on lipopolysaccharide (LPS)/d­galactosamine (D-GalN)-induced liver injury. The mice were pretreated with SSa 1 h before LPS/D-GalN treatment. The liver MPO, MDA, and the serum AST and ALT levels were tested by specific determination kits. The pro-inflammatory cytokines TNF-α and IL-1ß were tested by ELISA kits. The expression of NF-κB signaling pathway and LXRα were tested by western blot analysis. The results showed that SSa significantly reduced the levels of liver MPO, MDA, and serum AST, ALT levels induced by LPS/D-GalN. SSa also dose-dependently inhibited LPS/D-GalN-induced pro-inflammatory cytokines TNF-α and IL-1ß production. Furthermore, we found that SSa inhibited NF-κB signaling pathway activation induced by LPS/D-GalN. In addition, SSa dose-dependently increased the expression of LXRα. In conclusion, the results demonstrated that SSa had protective effect on liver injury and the anti-inflammatory mechanisms of SSa on LPS/D-GalN-induced liver injury may be due to its ability to increase LXRα expression. SSa might be a potential treatment for liver injury.

Down-regulation of LncRNA UCA1 alleviates liver injury in rats with liver cirrhosis.

OBJECTIVE: The purpose of this study is to explore the role of long non-coding RNA HULC (lncRNA HULC) in liver injury of rats with cirrhosis. METHODS: The rat model of liver cirrhosis was induced by dimethylnitrosamine (DMN), which was intraperitoneally injected with siRNA-negative control (NC) or HULC siRNA. HULC expression in rat liver tissues was detected by qRT-PCR. The amounts of alanine transaminase (ALT) and aspartate aminotransferase (AST) in serum and levels of malonyldialdehyde (MDA) and superoxide dismutase (SOD) in liver tissues were measured. TUNEL staining was used to determine hepatocyte apoptosis. Western blot analysis was used to detect the expression of Caspase-3, Bax, and Bcl-2 in liver tissues. qRT-PCR and ELISA were used to detect the mRNA levels and contents of IL-1ß and TNF-α in liver tissues and serum of rats, respectively. RESULTS: High expression of HULC was found in liver tissues of rats with liver cirrhosis. Downregulation of HULC reduced the contents of ALT and AST in serum of rats, inhibited liver tissue lesions and liver fibrosis in rats, suppressed apoptosis (lower expression of caspase-3 and Bax as well as higher BCL-2 expression) of hepatocytes in rats, and inhibited oxidative stress (decreased MDA and increased SOD) and inflammatory injury (decreased IL-1ß and TNF-α) in rats with cirrhosis. CONCLUSION: The findings in this study highlight that the expression of HULC is up-regulated in liver tissues of rats with cirrhosis, and down-regulation of UCA1 could inhibit liver injury in rats with cirrhosis.

Effect of Prepregnancy Obesity on Litter Size in Primiparous Minipigs.

Obesity is a public health problem in both developed and developing countries, and the negative effects of obesity on reproductive physiology have been highlighted recently. We evaluated the effects of porcine obesity index, sex hormones, and peptide hormones on litter size in various breeds of minipigs. Blood samples were collected from sedated 8-,10-, and 12-mo-old minipigs to measure preovulatory levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin) and peptide hormones (insulin-like growth factor, glucagon, cortisol, growth hormone, free thyroxine, free triiodothyronine, insulin, and leptin). We also measured weight, abdominal circumference, neck circumference, and body length and then calculated the porcine obesity index. Data were analyzed by one-way ANOVA, and means were compared by least significance difference testing. Pearson correlation between parameters and litter size was analyzed. Prepregnancy porcine obesity index and litter size were negatively correlated in primiparous minipigs. Litter size was influenced by luteinizing hormone, estradiol, progesterone, testosterone, prolactin, follicle-stimulating hormone, cortisol, insulin-like growth factor 1, growth hormone, free thyroxine, insulin, and leptin. In conclusion, prepregnancy obesity reduces litter size in primiparous minipigs.

Knockdown of AQP1 inhibits growth and invasion of human ovarian cancer cells.

Aquaporin 1 (AQP1), which is a water channel protein, has been demonstrated to have an important role in cell proliferation and migration of various cancers. However, its specific role in ovarian cancer remains to be elucidated. The present study demonstrated that AQP1 expression was elevated in the majority of patients with ovarian cancer compared with normal ovarian tissues. In addition, a short interfering (si)RNA targeting AQP1 was established, and transfected into the SKOV3 ovarian cancer cell line, to investigate the effects on cell viability, apoptosis, migration and invasion in the ovarian cancer cells using an MTT assay, flow cytometry, wound healing and Transwell invasion chamber assays, respectively. The results of the present study demonstrated that siRNA targeting AQP1 effectively downregulated AQP1 expression at the mRNA and protein levels, markedly suppressed cell viability, migration and invasion and promoted apoptosis of ovarian cancers cells. These results suggested that AQP1 may serve as a novel target for ovarian cancer treatment in the future.

Experience of Mowat-Wilson syndrome prenatal diagnosis for a Chinese family.

Mowat-Wilson syndrome (MWS) is a complex developmental disorder. We report the first prenatal diagnosis provided for a family in mainland China after identifying the causal mutation for the proband. Special focus on MWS-related organs during prenatal ultrasound scan is described which is extremely important for genetic counseling of parents.