Necrotizing enterocolitis: current understanding of the prevention and management.

Necrotizing enterocolitis (NEC) is one of the diseases in neonates, with a high morbidity and mortality rate, especially in preterm infants. This review aimed to briefly introduce the latest epidemiology, susceptibility factors, and clinical diagnosis and presentation of NEC. We also organized new prevention strategies by risk factors according to different pathogeneses and then discussed new treatment methods based on Bell's staging and complications, and the classification of mild to high severity based on clinical and imaging manifestations. Such a generalization will help clinicians and researchers to gain a deeper understanding of the disease and to conduct more targeted classification, grading prevention, and exploration. We focused on prevention and treatment of the early and suspected stages of NEC, including the discovery of novel biomarkers and drugs to control disease progression. At the same time, we discussed its clinical application, future development, and shortcomings.

Minimum clinically important differences in the Minnesota Living with Heart Failure questionnaire: from a study of heart failure patients treated with integrated Chinese and Western medicine.

Objective: The purpose of this study was to estimate the minimum clinically important differences (MCIDs) in the Minnesota Living with Heart Failure questionnaire (MLHFQ), which targeted patients with heart failure treated with integrated Chinese and Western medicine, as a means of helping doctors and patients judge the effectiveness of intervention. Methods: A total of 194 patients with chronic heart failure were recruited from three general hospitals in Beijing. Anchor-based and distribution-based approaches were used to estimate MCID. The anchor was SF-36 item 2 (HT, Health Transition), and the calculation methods included the mean change method, receiver operating characteristic (ROC) curve analysis, and linear regression model. For the distribution-based approaches, 0.2, 0.5, and 0.8 standardized response mean (SRM) values and standard error of measurement (SEM) value of 1 were used. Results: The correlation coefficients of the MLHFQ scale information and HT were 0.346-0.583. Different MCIDs were obtained by the mean change method, ROC curve, and linear regression model. The minimum MCID in the physical domain, emotional domain, and total scores were 3.6, 2.0, and 7.4, respectively; the maximum estimates were 9.5, 2.5, and 13.0, respectively; and the average estimates were 5.7, 2.2, and 10.0, respectively. The average estimates were close to the result of the 0.5 SRM or 1 SEM. Conclusion: We established MCIDs in the MLHFQ using anchor-based and distribution-based approaches. It was recommended to round the average estimates of anchor-based approaches up to the nearest whole number for the MCIDs of the MLHFQ physical domain, emotional domain, and total scores. The results were 6.0, 2.0, and 10.0, respectively.

Prediction models for overall and cancer-specific survival in patients with metastatic early-onset colorectal cancer: a population-based study.

PURPOSE: Metastatic early-onset colorectal cancer (EO-CRC) is on the rise, yet there is a dearth of predictive models for this disease. Therefore, it is crucial to develop a nomogram to aid in the early detection and management of metastatic colorectal cancer in young patients. METHODS: We retrieved data from the SEER database on patients with metastatic colorectal cancer aged 50 or younger between 2010 and 2017. The data were randomly allocated in a 7:3 ratio to training and validation cohorts, and univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS) at 1, 3, and 5 years. The nomograms were developed based on these factors, and their discriminatory and calibration capabilities were validated. Using the nomogram risk scores, patients were stratified into low-risk and high-risk groups. RESULTS: The study included 2470 patients with metastatic EO-CRC. Univariate and multivariate Cox regression analysis identified 12 independent risk factors that were included in the nomogram. The training cohort had a consistency index (C-index) of 0.71, while the validation cohort had a C-index of 0.70, demonstrating good predictive accuracy. Calibration plots showed a high level of consistency between the observed and predicted values, with overlapping plots along the diagonal. The decision curve analysis (DCA) revealed that the nomogram had a high clinical application value. CONCLUSIONS: The novel nomograms were created to predict the prognosis of patients with metastatic EO-CRC, which can aid clinicians in developing more effective treatment strategies and contribute to more accurate prognostic assessments.

Doppler Echocardiography Combined with NTproBNP/BNP in the Diagnosis of Pulmonary Artery Hypertension Associated with Congenital Heart Disease.

Background: Pulmonary artery hypertension (PAH) is a common complication of congenital heart disease (CHD) and is associated with worse outcomes and increased mortality. The Doppler echocardiography (DE) is a commonly used imaging tool for both diagnosis and follow-up examination of PAH. Here is to evaluate the diagnostic performance of DE combined with NTproBNP/BNP as screening strategy in PAH patients with CHD. Methods: A retrospective study in 64 patients with CHD has been carried out to compare estimate pulmonary artery systolic pressure (PASP) measured with DE to that measured with right heart catheterization (RHC). The Pearson correlation analyses were used to calculate the correlation coefficients between RHC and DE. The Bland-Altman analyses were carried out to assess the agreement between the two methods. ROC analyses were used to evaluate the diagnostic performance of DE, NTproBNP/BNP, and DE combined with NTproBNP/BNP. Results: Our data have demonstrated that a mild correlation (r = 0.4401, P < 0.01) was observed between PASP (78.1 ± 29.0 mmHg) measured during RHC and PASP (74.9 ± 19.7 mmHg) as estimated using DE. The Bland-Altman analysis demonstrated that the bias for DE PASP estimates was 3.2 mmHg with 95% limits of agreement ranging from -49.53 to 55.90 mmHg. The results of DE showed an AUC of 0.848 (95% CI = 0.666-1; P < 0.001), the sensitivity of which was 98.3% and the specificity was 77.8%. The AUC of NTproBNP/BNP for the identification of PAH was 0.804 (95% CI = 0.651-0.956; P < 0.001), the sensitivity of which was 81.4% and the specificity was 87.5%. The AUC of DE combined with NTproBNP/BNP was 0.857 (95% CI = 0.676-1; P < 0.001), of which sensitivity was 100% and specificity was 77.8%. The positive predictive value (PPV) and negative predictive value (NPV) were 96.6% and 100%, respectively. Conclusions: Our study shows that the Doppler echocardiography combined with NTproBNP/BNP has better diagnostic performance in pulmonary artery hypertension associated with congenital heart disease, especially when DE negative screening in PAH patients.

Low COVID-19 vaccine coverage and guardian acceptance among pediatric transplant recipients.

To investigate COVID-19 vaccine coverage in immunosuppressed children, assess guardians' intention to vaccinate children, and determine reasons and associated factors. In addition, we attempted to capture the characteristics of them with Omicron. We obtained the vaccination coverage and guardian vaccine acceptance among pediatric transplant recipients through a web-based questionnaire conducted from April 12 to 28, 2022, and performed the statistical analysis. Seven organ transplant recipient children with Omicron were also clinically analyzed. The three-dose vaccine coverage for liver transplant (n = 563) and hematopoietic stem cell transplantation (n = 122) recipient children was 0.9% and 4.9%, and guardian vaccine acceptance was 63.8%. Independent risk factors for vaccine acceptance were the child's age, geographic location, type of transplant, guardian's vaccination status, guardian's level of distress about epidemic events, guardian's risk perception ability, anxiety, and knowledge of epidemic control. The main reasons for vaccine hesitancy were fear of vaccine-induced adverse events and doubts about efficacy. Ultimately, most children infected with Omicron have mild or no symptoms and are infected by intra-family. Since vaccine coverage and guardian acceptance are lowest among liver transplant children, and the infected are mainly intra-family, we should devise more targeted education and vaccination instructions for their guardians.

LncRNA Osilr9 coordinates promoter DNA demethylation and the intrachromosomal loop structure required for maintaining stem cell pluripotency.

Nuclear reprogramming of somatic cells into a pluripotent status has the potential to create patient-specific induced pluripotent stem cells for regenerative medicine. Currently, however, the epigenetic mechanisms underlying this pluripotent reprogramming are poorly understood. To delineate this epigenetic regulatory network, we utilized a chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to identify long noncoding RNAs (lncRNAs) embedded in the 3-dimensional intrachromosomal architecture of stem cell core factor genes. By combining CRIST-seq and RNA sequencing, we identified Oct4-Sox2 interacting lncRNA 9 (Osilr9) as a pluripotency-associated lncRNA. Osilr9 expression was associated with the status of stem cell pluripotency in reprogramming. Using short hairpin RNA (shRNA) knockdown, we showed that this lncRNA was required for the optimal maintenance of stem cell pluripotency. Overexpression of Osilr9 induced robust activation of endogenous stem cell core factor genes in fibroblasts. Osilr9 participated in the formation of the intrachromosomal looping required for the maintenance of pluripotency. After binding to the Oct4 promoter, Osilr9 recruited the DNA demethylase ten-eleven translocation 1, leading to promoter demethylation. These data demonstrate that Osilr9 is a critical chromatin epigenetic modulator that coordinates the promoter activity of core stem cell factor genes, highlighting the critical role of pluripotency-associated lncRNAs in stem cell pluripotency and reprogramming.

Comparison of EQ-5D-5L and EORTC QLU-C10D utilities in gastric cancer patients.

BACKGROUND: To compare measurement properties of the utility scores derived from various country-specific value sets of EQ-5D-5L (5L) and EORTC QLU-C10D (10D) in gastric cancer patient. METHODS: The study used cross-sectional data of 243 Chinese gastric cancer patients who completed both 5L and EORTC QLQ-C30. Utility score of QLU-C10D is generated from all the available QLU-C10D value sets currently; the score of 5L is derived from the corresponding 5L value sets for the countries with both the 5L and QLU-C10D value sets and the Chinese 5L value set. Convergent validity was evaluated by testing their correlations with the VAS score. Known-group validity was assessed by comparing the utility scores the patients with different severities. Their relative efficiency (RE) was also compared. RESULTS: Correlation coefficient of 5L and QLU-C10D utility scores with VAS ranged from 0.54 to 0.59, and 0.55 to 0.63, respectively. Both the utility scores were in general able to discriminate the patients with different severities; and 5L utility score had higher RE in the majority of known-groups. CONCLUSION: EQ-5D-5L and QLU-C10D utility scores were different and, thus, non-swappable. They possess similar convergent validity and known-group validity; while EQ-5D-5L scores may have better discriminative power.

Cancer-Secreted Exosomal MiR-620 Inhibits ESCC Aerobic Glycolysis via FOXM1/HER2 Pathway and Promotes Metastasis.

Background: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide. MicroRNAs (MiRNAs) have been reported to regulate cell functions through exosomes. Through the Gene Expression Omnibus (GEO) database, miR-620 was selected as a serum miRNA highly expressed in ESCC, but its detailed role in ESCC has not been explored. Tumor-secreted miRNAs have been reported to promote cancer metastasis through reprogramming the aerobic glycolysis of lung fibroblasts. Therefore, we intended to verify whether exosomal miR-620 secreted in ESCC cells may regulate the aerobic glycolysis of lung fibroblasts. Methods: The effect of miR-620 on the aerobic glycolysis of ESCC cells was firstly verified through bioinformatics prediction and mechanism assays. Exosomes secreted from ESCC cells was detected, and the influence of exosomal miR-620 in regulating the aerobic glycolysis of lung fibroblasts was then verified both in vitro and in vivo. Results: MiR-620 inhibited ESCC malignancy and suppressed the aerobic glycolysis of ESCC cells via targeting Forkhead box M1 (FOXM1) and human epidermal growth factor receptor 2 (HER2). Moreover, exosomal miR-620 was highly secreted in ESCC and could regulate HFL1 aerobic glycolysis via FOXM1/HER2 signaling. Furthermore, exosomal miR-620 could promote ESCC metastasis by reprogramming the aerobic glycolysis of lung fibroblasts (HFL1). Conclusion: Exosomal miR-620 secreted by ESCC cells inhibited the aerobic glycolysis via FOXM1/HER2 axis and promoted cancer metastasis.

Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with heart failure.

PURPOSE: Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with chronic heart failure, and to obtain the health utility value for health economic assessment. METHODS: Four statistical algorithms, including ordinary least square method (OLS), Tobit model, robust MM estimator (MM) and censored least absolute deviations (CLAD), were used to establish the alternative model. Models were validated by using a tenfold cross-validation technique. The mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate the prediction performance of the model. The Spearman correlation coefficient and Intraclass Correlation Coefficients (ICC) were used to examine the relationship between the predicted and observed SF-6Dv2 values. RESULTS: A total of 195 patients with chronic heart failure were recruited from 3 general hospitals in Beijing. The MLHFQ summary score and domain scores of the study sample were negatively correlated with SF-6Dv2 health utility value. The OLS regression model established based on the MLHFQ domain scores was the optimal fitting model and the predicted value was highly positively correlated with the observed value. CONCLUSION: The MLHFQ can be mapped to SF-6Dv2 by OLS, which can be used for health economic assessment of cardiovascular diseases such as chronic heart failure.

Paeoniflorin Upregulates Mitochondrial Thioredoxin of Schwann Cells to Improve Diabetic Peripheral Neuropathy Indicated by 4D Label-Free Quantitative Proteomics.

Diabetic peripheral neuropathy (DPN) is a diabetic complication characterized by demyelination. The pathogenesis of DPN has not been fully elucidated, thus lacking therapies. In the current study, we aimed to confirm whether paeoniflorin (PF) could improve DPN by upregulating mitochondrial thioredoxin (Trx2) based on 4D Label-free proteomic experiments of Schwann cells (SCs) mitochondria. Firstly, PF increased the expression of mitochondrial processing peptidase α (Pmpca) and small ubiquitin-related modifier 1 (Sumo1) to increase mitochondrial protein processing of Trx2. Then, PF increased the protein expression of Trx reductase 2 (TrxR2) and peroxiredoxin 3 (Prx3), which belong to mitochondrial Trx systems. Accordingly, PF decreased mitochondrial reactive oxygen species (ROS) while increasing mtDNA and mitochondrial membrane potential to improve mitochondria function under high glucose environment. Furthermore, total glucosides of paeony capsules (TGP), containing more than 90% PF, increased the Trx2, TrxR2, and Prx3 levels in sciatic nerve of DPN rats, thus reducing demyelination as well as improving mechanical pain threshold, thermal pain threshold, motor nerve conduction velocity (MNCV), and sensor nerve conduction velocity (SNCV). Overall, these results suggest that PF could provide protection for DPN by upregulating Trx2.

Prevalence, antimicrobial resistance, and genotype diversity of Salmonella isolates recovered from retail meat in Hebei Province, China.

This study investigated the prevalence of Salmonella in 210 retail meat samples (105 raw chicken and 105 raw pork) collected from supermarkets and wet markets in 13 areas of Hebei Province, China, from June to October 2018. Whole-genome sequencing was performed on all 125 Salmonella isolates to investigate their genetic relationship. Core genome multilocus sequence typing of 77 representative isolates was used to further elucidate the genetic relatedness among the Salmonella isolated from retail meat. The mean detection rate of Salmonella in all samples was 59.5% (125/210). The prevalence of Salmonella was 53.3% (56/105) in chicken and 65.7% (69/105) in pork. Chicken and pork samples collected in July had the highest detection rate of Salmonella among the sampling months. The isolates were assigned to 19 serotypes, with S. Derby, S. London, and S. Thompson being the most frequent serotypes. Resistance to tetracycline (primarily used for the treatment of bacterial infections) was observed in 89.6% of the isolates, and 84.0% were resistant to doxycycline (also a tetracycline antibiotic) or gemifloxacin (commonly used for clinical treatment of human acute bronchitis). More than 80% of the isolates were multidrug resistant. A total of 21 sequence types were identified. Sequence type 40 (ST-40), the predominant genotype among all isolates, was found only in pork; the sequence types of chicken isolates were more diverse. A total of 58 different antibiotic resistance genes (ARGs) were detected in the 125 isolates. Most types of ARGs were associated with aminoglycoside and ß-lactam resistance. Nevertheless, the tetracycline resistance gene tet(A) was the most frequently occurring ARG in all isolates at 78.4%. Multiple isolates of ST-26 contained 20 ARGs. All isolates of ST-40 were divided into two clusters, with at least 160 allelic differences between them. The findings highlight the need to continually monitor ARGs in foodborne Salmonella with particular emphasis on ST-40 and ST-26; the monitoring should include as many retail meat types as possible in the study area.

The Fitting Optimization Path Analysis on Scale Missing Data: Based on the 507 Patients of Poststroke Depression Measured by SDS.

OBJECTIVE: To explore the optimal fitting path of missing data of the Scale to make the fitting data close to the real situation of patients' data. METHODS: Based on the complete data set of the SDS of 507 patients with stroke, the data simulation sets of Missing Completely at Random (MCAR), Missing at Random (MAR), and Missing Not at Random (MNAR) were constructed by R software, respectively, with missing rates of 5%, 10%, 15%, 20%, 25%, 30%, 35%, and 40% under three missing mechanisms. Mean substitution (MS), random forest regression (RFR), and predictive mean matching (PMM) were used to fit the data. Root mean square error (RMSE), the width of 95% confidence intervals (95% CI), and Spearman correlation coefficient (SCC) were used to evaluate the fitting effect and determine the optimal fitting path. RESULTS: when dealing with the problem of missing data in scales, the optimal fitting path is ① under the MCAR deletion mechanism, when the deletion proportion is less than 20%, the MS method is the most convenient; when the missing ratio is greater than 20%, RFR algorithm is the best fitting method. ② Under the Mar mechanism, when the deletion ratio is less than 35%, the MS method is the most convenient. When the deletion ratio is greater than 35%, RFR has a better correlation. ③ Under the mechanism of MNAR, RFR is the best data fitting method, especially when the missing proportion is greater than 30%. In reality, when the deletion ratio is small, the complete case deletion method is the most commonly used, but the RFR algorithm can greatly expand the application scope of samples and save the cost of clinical research when the deletion ratio is less than 30%. The best way to deal with data missing should be based on the missing mechanism and proportion of actual data, and choose the best method between the statistical analysis ability of the research team, the effectiveness of the method, and the understanding of readers.

Paeoniflorin Effect of Schwann Cell-Derived Exosomes Ameliorates Dorsal Root Ganglion Neurons Apoptosis through IRE1α Pathway.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes but its pathogenesis is not fully clarified. Endoplasmic reticulum (ER) stress has been confirmed to be involved in the development of DPN. Dorsal root ganglion neuron (DRGn) is the target cell of DPN injure in the peripheral neurons system. Schwann cell (SCs)-derived exosomes (SC-EXOs) can carry IRE1α signal transduction factors in ER stress to DRGn. The aim of this study is to investigate the effect of SC-EXOs treated with paeoniflorin (PF) on DRGn stimulated by high glucose. METHODS: SCs were divided into Control group (Control), 150 mM glucose group (HG), high osmotic pressure group (HOP), and low, middle, and high dose PF group (PF1, PF10, and PF100). Exosomes were obtained from SCs by ultracentrifugation and identified according to marker proteins, including CD63, Alix, Hsp70, and TSG101. ER stress initiating factor GRP78, the IRE1α pathway information transmission factor IRE1α, and the phosphorylation level of IRE1α were detected by Western blot, DRGn is divided into Control group (Control), 50 mM glucose group + Control exosomes group (HG + EXOs Control), 50 mM glucose group (HG), and 50 mM glucose group + administration exosomes group (HG + EXOs PF1, HG + EXOs PF10, and HG + EXOs PF100); ER morphology of primary DRGn was observed by using the transmission electron microscope, the level of DRGn apoptosis was analyzed by TUNEL, and the downstream proteins of ER stress including CHOP, XBP1S, JNK, and p-JNK in DRG and the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, and Caspase-12 were measured by Western blot. RESULTS: Compared with the exosomes in the HG group, the exosomes after the intervention of PF can significantly reduce the expression of GRP78, IRE1α, and the phosphorylation level of IRE1α(P < 0.05); compared with the DRGn in the HG group, the SC-EXOs treated with PF could regulate the expression of proteins downstream of IRE1α pathway in ER stress (P < 0.05 or P < 0.01), improve the morphological integrity of ER, and reduce apoptosis in DRGn (P < 0.05 or P < 0.01). CONCLUSION: PF regulates the information of ER stress carried by SC-EXOs and further affects downstream of IRE1α pathway in DRGn, thus reducing ER stress-induced apoptosis. PF can interfere with DPN through affecting information communication carried by EXOs between SCs and DRGn.

Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network.

BACKGROUND: A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in the Oct4 promoter. RESULTS: We identify Platr10 as an Oct4 - Sox2 binding lncRNA that is activated in somatic cell reprogramming. Platr10 is essential for the maintenance of pluripotency, and lack of this lncRNA causes stem cells to exit from pluripotency. In fibroblasts, ectopically expressed Platr10 functions in trans to activate core stem cell factor genes and enhance pluripotent reprogramming. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we show that Platr10 interacts with multiple pluripotency-associated genes, including Oct4, Sox2, Klf4, and c-Myc, which have been extensively used to reprogram somatic cells. Mechanistically, we demonstrate that Platr10 helps orchestrate intrachromosomal promoter-enhancer looping and recruits TET1, the enzyme that actively induces DNA demethylation for the initiation of pluripotency. We further show that Platr10 contains an Oct4 binding element that interacts with the Oct4 promoter and a TET1-binding element that recruits TET1. Mutation of either of these two elements abolishes Platr10 activity. CONCLUSION: These data suggest that Platr10 functions as a novel chromatin RNA molecule to control pluripotency in trans by modulating chromatin architecture and regulating DNA methylation in the core stem cell factor network.

Evaluating health-related quality of life in gastric cancer patients in Suzhou, China.

BACKGROUND: Health-related quality of life (HRQOL) has become an important part of the evaluation of clinical efficacy and prognosis in gastric cancer. This study aimed to assess the HRQOL of patients with gastric cancer using the a five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) and explore the factors influencing patients' perceived quality of life. For those significant factors, we can take appropriate measures to intervene to extend patient survival and improve the quality of life. METHODS: A cross-sectional questionnaire survey was administered to 243 patients with gastric cancer in the First Affiliated Hospital of Suzhou University from December 2018 to December 2020. HRQOL was measured by the Chinese version of the EQ-5D-5L. Nonparametric test analyses and a Tobit regression model were used to identify the independent variables associated with the EQ-5D-5L utility scores. RESULTS: In this research, the mean score was 0.810, and the median was 0.893. Approximately 25% of patients reported no problems at all in any of the five dimensions. Problems in pain and discomfort were the most frequently reported (64.2%). Nonparametric test analyses showed that patients who did not have health insurance, or who had a history of alcohol use, a family history of cancer, had received surgery only, or had an interval of less than 1 week between taking this survey and their last treatment, demonstrated lower EQ-5D-5L scores. The Tobit regression model confirmed that health insurance, family history, and treatment were significantly associated with EQ-5D-5L scores. CONCLUSIONS: The HRQOL of gastric cancer patients can be measured by EQ-5D-5L, and the results may provide a guide for choosing an appropriate individualized treatment plan.

Corrigendum: Tang Luo Ning, a Traditional Chinese Compound Prescription, Ameliorates Schwannopathy of Diabetic Peripheral Neuropathy Rats by Regulating Mitochondrial Dynamics In Vivo and In Vitro.

[This corrects the article DOI: 10.3389/fphar.2021.650448.].

Tang Luo Ning, a Traditional Chinese Compound Prescription, Ameliorates Schwannopathy of Diabetic Peripheral Neuropathy Rats by Regulating Mitochondrial Dynamics In Vivo and In Vitro.

Tang Luo Ning (TLN), a traditional Chinese compound prescription, has been used clinically to treat diabetic peripheral neuropathy (DPN) in China. However, the exact mechanisms remain unclear. The objective of this study is to unravel the effects of TLN on mitochondrial dynamics of DPN in streptozotocin-induced rat models and Schwann cells cultured in 150 mM glucose. Mitochondrial function was determined by Ca2+ and ATP levels of streptozotocin (STZ)-induced DPN rats and mitochondria structure, mitochondrial membrane potential (MMP), and mtDNA of high glucose incubated SCs. Mitochondrial dynamics protein including mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), optic atrophy 1 (Opa1), and dynamin-related protein 1 (Drp1) were investigated using Western blot or immunofluorescence. Myelin basic protein (MBP), myelin protein zero (MPZ), and sex-determining region Y (SRY)-box 10 (Sox10) were measured to represent schwannopathy. Our results showed that TLN increased ATP levels (0.38 of model, 0.69 of HTLN, 0.61 of LTLN, P＜0.01; 0.52 of 150 mM glucose, 1.00 of 10% TLN, P＜0.01, 0.94 of 1% TLN, P＜0.05), MMP (0.56 of 150 mM glucose, P＜0.01, 0.75 of 10% TLN, P＜0.05, 0.83 of 1% TLN, P＜0.01), and mtDNA (0.32 of 150 mM glucose, 0.43 of 10% TLN, P＜0.01) while decreased Ca2+ (1.54 of model, 1.06 of HTLN, 0.96 of LTLN, P＜0.01) to improve mitochondrial function in vivo and in vitro. TLN helps maintain balance of mitochondrial dynamics: it reduces the mitochondria number (1.60 of 150 mM glucose, 1.10 of 10% TLN, P＜0.01) and increases the mitochondria coverage (0.51 of 150 mM glucose, 0.80 of 10% TLN, 0.87 of 1% TLN, P＜0.01), mitochondrial network size (0.51 of 150 mM glucose, 0.95 of 10% TLN, 0.94 of 1% TLN, P＜0.01), and branch length (0.63 of 150 mM glucose, P＜0.01, 0.73 of 10% TLN, P＜0.05, 0.78 of 1% TLN, P＜0.01). Further, mitochondrial dynamics-related Mfn1 (0.47 of model, 0.82 of HTLN, 0.77 of LTLN, P＜0.01; 0.42 of 150 mM glucose, 0.56 of 10% TLN, 0.57 of 1% TLN, P＜0.01), Mfn2 (0.40 of model, 0.84 of HTLN, 0.63 of LTLN, P＜0.01; 0.46 of 150 mM glucose, 1.40 of 10% TLN, 1.40 of 1% TLN, P＜0.01), and Opa1 (0.58 of model, 0.71 of HTLN, 0.90 of LTLN, P＜0.01; 0.69 of 150 mM glucose, 0.96 of 10% TLN, 0.98 of 1% TLN, P＜0.05) were increased, while Drp1 (1.39 of model, 0.96 of HTLN, 1.18 of LTLN, P＜0.01; 1.70 of 150 mM glucose, 1.20 of 10% TLN, 1.10 of 1% TLN, P＜0.05), phosphorylated Drp1 (2.61 of model, 1.44 of HTLN, P＜0.05; 2.80 of 150 mM glucose, 1.50 of 10% TLN, 1.30 of 1% TLN, P＜0.01), and Drp1 located in mitochondria (1.80 of 150 mM glucose, 1.00 of 10% TLN, P＜0.05) were decreased after treatment with TLN. Additionally, TLN improved schwannopathy by increasing MBP (0.50 of model, 1.05 of HTLN, 0.94 of HTLN, P＜0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, P＜0.01, 0.72 of 1% TLN, P＜0.05), Sox101 (0.41 of model, 0.99 of LTLN, P＜0.01; 0.48 of 150 mM glucose, 0.65 of 10% TLN, P＜0.05, 0.69 of 1% TLN, P＜0.01), and MPZ (0.48 of model, 0.66 of HTLN, 0.55 of HTLN, P＜0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, P＜0.01, 0.75 of 1% TLN, P＜0.05) expressions. In conclusion, our study indicated that TLN's function on DPN may link to the improvement of the mitochondrial dynamics, which provides scientific evidence for the clinical application.

The cyclic expansion and contraction characteristics of a loess slope and implications for slope stability.

Loess covers approximately 6.6% of China and forms thick extensive deposits in the northern and northwestern parts of the country. Natural erosional processes and human modification of thick loess deposits have produced abundant, potentially unstable steep slopes in this region. Slope deformation monitoring aimed at evaluating the mechanical behavior of a loess slope has shown a cyclic pattern of contraction and expansion. Such cyclic strain change on the slope materials can damage the loess and contribute to slope instability. The site showing this behavior is a 70-m high loess slope near Yan'an city in Shanxi Province, northwest China. A Ground-Based Synthetic Aperture Radar (GB-SAR) sensor and a displacement meter were used to monitor this cyclic deformation of the slope over a one-year period from September 2018 to August 2019. It is postulated that this cyclic behavior corresponds to thermal and moisture fluctuations, following energy conservation laws. To investigate the validity of this mechanism, physical models of soil temperature and moisture measured by hygrothermographs were used to simulate the observed cyclic deformations. We found good correlations between the models based on the proposed mechanism and the exhibited daily and annual cyclic contraction and expansion. The slope absorbed energy from the time of maximum contraction to the time of maximum expansion, and released energy from the time of maximum expansion to the time of maximum contraction. Recoverable cyclic deformations suggest stresses in the loess are within the elastic range, and non-recoverable cyclic deformations suggest damage of the loess material (breakage of bonds between soil grains), which could lead to instability. Based on these observations and the models, we developed a quantitative relationship between weather cycles and thermal deformation of the slope. Given the current climate change projections of temperature increases of up to 3.5 °C by 2100, the model estimates the loess slope to expand about 0.35 mm in average, which would be in addition to the current cyclic "breathing" behavior experienced by the slope.

Role of hypoxia inducible factor-1 in cancer stem cells (Review).

Cancer stem cells (CSCs) have been found to play a decisive role in cancer recurrence, metastasis, and chemo­, radio­ and immuno­resistance. Understanding the mechanism of CSC self­renewal and proliferation may help overcome the limitations of clinical treatment. The microenvironment of tumor growth consists of a lack of oxygen, and hypoxia has been confirmed to induce cancer cell invasion, metastasis and epithelial­mesenchymal transition, and is usually associated with poor prognosis and low survival rates. Hypoxia inducible factor­1 (HIF­1) can be stably expressed under hypoxia and act as an important molecule to regulate the development of CSCs, but the specific mechanism remains unclear. The present review attempted to explain the role of HIF­1 in the generation and maintenance of CSCs from the perspective of epigenetics, metabolic reprogramming, tumor immunity, CSC markers, non­coding RNA and signaling pathways associated with HIF­1, in order to provide novel targets with HIF­1 as the core for clinical treatment, and extend the life of patients.