Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease.

Purpose: To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Methods: Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Results: Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. Conclusion: A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.

Analysis of the Ability of a Distal Tibial Anatomical Locking Plate to Capture the Distal Tibial Fragments in Patients with Pilon Fractures.

OBJECTIVE: Although pilon fractures are rare in clinical practice, they are difficult to treat because of their complexity. Effective fixation of the fracture fragment is the key to the treatment of pilon fractures. Plate osteosynthesis is common clinically, but there are many types of plates and the evaluation of the effect of fixation plates is not comprehensive. This study attempted to compare the capture effect of different fixation plates on the fracture fragments based on 3D modeling and fine distinctions of fracture fragments. METHODS: The computed tomography (CT) images before treatment of 127 patients with pilon fractures from January 2019 to December 2021 were retrospectively collected. The fracture lines were mapped and digitally displayed as 3D images using MIMICS 21 software. APLUS distal tibia anatomical locking plate (Plate A) and ZIMMER distal tibia anatomical plate (Plate B) were placed on a pseudo-bone model and CT scans were used to determine the number of screws in the major and minor fragments of pilon fractures. The frequency of the two plates capturing the fracture fragments was recorded. RESULTS: Under Assumption 1 or 2, Plate A performed significantly better than Plate B in capturing the major, Chaput, Volkmann, medial malleolus, and die-punch fracture fragments. Plate A captured markedly more minor fragments than Plate B under Assumption 2 but was not significantly different from Plate B under Assumption 1. Plate A or Plate B showed no obvious difference between major and minor capture rates under the same assumption, and A1 or B1 showed a markedly higher capture rate compared with A2 or B2. In addition, there was a significant positive correlation between the major capture rate and the major fragments in B1, and a significant negative correlation between the minor capture rate and the minor fragments in Plates A and B. However, there was no correlation between the major capture rate of Plate A and the major fragments. CONCLUSION: The APLUS distal tibial anatomical locking plate is superior to the ZIMMER distal tibia anatomical plate in the ability to capture distal tibial fragments in pilon fracture cases.

Functional Characterization of the Nuclear Receptor Gene SaE75 in the Grain Aphid, Sitobion avenae.

Ecdysteroid hormones are key regulators of insect development and metamorphosis. Ecdysone-inducible E75, a major component of insect ecdysone signaling pathway, has been well characterized in holometabolous insects, however, barely in hemimetabolous species. In this study, a total of four full-length E75 cDNAs from the English grain aphid, Sitobion avenae, were identified, cloned, and characterized. The four SaE75 cDNAs contained 3048, 2625, 2505, and 2179 bp open reading frames (ORF), encoding 1015, 874, 856, and 835 amino acids, respectively. Temporal expression profiles showed that SaE75 expression was low in adult stages, while high in pseudo embryo and nymphal stages. SaE75 was differentially expressed between winged and wingless morphs. RNAi-mediated suppression of SaE75 led to substantial biological impacts, including mortality and molting defects. As for the pleiotropic effects on downstream ecdysone pathway genes, SaHr3 (hormone receptor like in 46) was significantly up-regulated, while Sabr-c (broad-complex core protein gene) and Saftz-f1 (transcription factor 1) were significantly down-regulated. These combined results not only shed light on the regulatory role of E75 in the ecdysone signaling pathway, but also provide a potential novel target for the long-term sustainable management of S. avenae, a devastating global grain pest.

A retrospective comparison of double-hooked locking plates versus non-locking plates in minimally invasive percutaneous plate osteosynthesis for the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures.

BACKGROUND: Surgical approach and fixation material are crucial in the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures. This study compared the efficacy of double-hooked locking plates and anatomic plates in minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures. METHODS: Clinical data were collected from 96 patients diagnosed with comminuted distal fibular fractures accompanied by tibial Pilon fractures who had undergone MIPPO. Patients in the study group (n = 48) received double-hooked locking plate fixations and the control group (n = 48) received anatomical plate fixations. The operating time, intraoperative bleeding, length of hospital stays, full weight-bearing time, fracture healing time and complication rates in the two groups were compared. The quality of fracture reduction was evaluated using the Burwell-Chamley imaging scoring system; the ankle function was assessed based on the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score. RESULTS: Patients in the study group had shorter operating time, less bleeding, significantly shorter hospital stays, and shorter time to full weight-bearing as well as fracture healing compared to the control group (P < 0.05). Additionally, the post-operative complication rates were significantly lower in the study group (6.16% vs. 22.92%) (P < 0.05), but there was no significant difference in the fracture reduction rate between the two groups (P > 0.05). Patients in the study group experienced better ankle recovery than those in the control group (93.75% vs. 75.00%) (P < 0.05). CONCLUSION: Double-hooked locking plates have advantages in the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures during MIPPO due to their shorter operating time and less intraoperative bleeding, as well as shorter hospital stays, full weight-bearing time and fracture healing time, fewer complications and better ankle recovery. Therefore, double-hooked locking plates are worthy of clinical application.

Prognostic value and immunological role of FOXM1 in human solid tumors.

FOXM1 acts as an oncogenic transcription factor and is involved in multiple hallmarks of human malignancies. Recent studies have demonstrated that FOXM1 is upregulated and correlated with poor prognosis in a majority of cancers. However, there are few pan-cancer analyses of FOXM1. This study aimed to investigate the expression profiles and clinical significance of FOXM1 in 31 types of solid tumors. We explored the expression profiles and the prognostic value of FOXM1 in pan-cancer across The Cancer Genome Atlas (TCGA). We further used lung adenocarcinoma (LUAD) tissues combined with quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) for experimental validation of FOXM1 expression. Besides, we verified the function of FOXM1 in a lung cancer cell line. Gene set enrichment analysis (GSEA) was conducted to explore signaling pathways related to FOXM1 expression. We observed that up-regulated FOXM1 was significantly related to poor survival in most tumors. Furthermore, there are significant correlations between FOXM1 expression and the infiltrating levels of different types of immune cells, TMB, MSI and immune checkpoint genes in a variety of cancers. Additional analysis based on IMvigor 210 cohort confirmed that patients with high level of FOXM1 exhibited a superior response to anti-PD-L1 therapy, and had a prolonged OS. In conclusion, this study indicated that FOXM1 could serve as a prognostic biomarker for most types of cancers and played a crucial role in the tumor immune microenvironment.

Bioinformatics prediction and experimental verification of key biomarkers for diabetic kidney disease based on transcriptome sequencing in mice.

Background: Diabetic kidney disease (DKD) is the leading cause of death in people with type 2 diabetes mellitus (T2DM). The main objective of this study is to find the potential biomarkers for DKD. Materials and Methods: Two datasets (GSE86300 and GSE184836) retrieved from Gene Expression Omnibus (GEO) database were used, combined with our RNA sequencing (RNA-seq) results of DKD mice (C57 BLKS-32w db/db) and non-diabetic (db/m) mice for further analysis. After processing the expression matrix of the three sets of data using R software "Limma", differential expression analysis was performed. The significantly differentially expressed genes (DEGs) (-logFC- > 1, p-value < 0.05) were visualized by heatmaps and volcano plots respectively. Next, the co-expression genes expressed in the three groups of DEGs were obtained by constructing a Venn diagram. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were further analyzed the related functions and enrichment pathways of these co-expression genes. Then, qRT-PCR was used to verify the expression levels of co-expression genes in the kidney of DKD and control mice. Finally, protein-protein interaction network (PPI), GO, KEGG analysis and Pearson correlation test were performed on the experimentally validated genes, in order to clarify the possible mechanism of them in DKD. Results: Our RNA-seq results identified a total of 125 DEGs, including 59 up-regulated and 66 down-regulated DEGs. At the same time, 183 up-regulated and 153 down-regulated DEGs were obtained in GEO database GSE86300, and 76 up-regulated and 117 down-regulated DEGs were obtained in GSE184836. Venn diagram showed that 13 co-expression DEGs among the three groups of DEGs. GO analysis showed that biological processes (BP) were mainly enriched inresponse to stilbenoid, response to fatty acid, response to nutrient, positive regulation of macrophage derived foam cell differentiation, triglyceride metabolic process. KEGG pathway analysis showed that the three major enriched pathways were cholesterol metabolism, drug metabolism-cytochrome P450, PPAR signaling pathway. After qRT-PCR validation, we obtained 11 genes that were significant differentially expressed in the kidney tissues of DKD mice compared with control mice. (The mRNA expression levels of Aacs, Cpe, Cd36, Slc22a7, Slc1a4, Lpl, Cyp7b1, Akr1c14 and Apoh were declined, whereas Abcc4 and Gsta2 were elevated). Conclusion: Our study, based on RNA-seq results, GEO databases and qRT-PCR, identified 11 significant dysregulated DEGs, which play an important role in lipid metabolism and the PPAR signaling pathway, which provide novel targets for diagnosis and treatment of DKD.

High Expression of EIF4G2 Mediated by the TUG1/Hsa-miR-26a-5p Axis Is Associated with Poor Prognosis and Immune Infiltration of Gastric Cancer.

Objective: Eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) is involved in the occurrence and development of various tumors. However, the effect of EIF4G2 in gastric cancer (GC) has not been fully explored. The purpose of this study was to explore the function and mechanism of EIF4G2 in GC. Methods: The Tumor Immune Estimation Resource 2.0 database was used to analyze EIF4G2 expression in various cancers and the relationship between EIF4G2 expression and tumor-infiltrating immune cells. Gene Expression Profiling Interactive Analysis was utilized to assess the EIF4G2 expression level and its effect on survival in GC. UALCAN was conducted to analyze EIF4G2 expression in various subgroups of GC. The Kaplan-Meier plotter was employed for survival analysis. Receiver operator characteristic (ROC) curve analysis was applied to evaluate the diagnostic role of EIF4G2 in GC. LinkedOmics was used to identify the co-expressed genes and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The Tumor-Immune System Interaction database was employed to analyze the correlation between EIF4G2 expression and tumor-infiltrating lymphocytes. The starBase web platform was used to predict the upstream microRNAs and long noncoding RNAs. Results: EIF4G2 expression was upregulated in GC tissues compared to normal controls. High expression of EIF4G2 indicated poor prognosis in GC. ROC analysis revealed that EIF4G2 had good diagnostic ability to distinguish GC from normal tissues. Immune infiltration analysis indicated that EIF4G2 expression may be involved in the modulation of tumor immune infiltration in GC. Finally, we determined that the Taurine Upregulated 1 (TUG1)/hsa-miR-26a-5p/EIF4G2 axis was the most likely regulatory pathway involved in GC development. Conclusions: EIF4G2 was upregulated in GC and elevated expression of EIF4G2 indicated unfavorable prognosis. Moreover, EIF4G2 expression may be involved in the regulation of tumor immune cell infiltration. The TUG1/hsa-miR-26a-5p axis is a likely upstream regulatory mechanism of EIF4G2 in GC. EIF4G2 may thus serve as a prognosis biomarker and present a new therapeutic target.

Impact of COVID-19 Pandemic on Elevated Anxiety Symptoms of Maintenance Hemodialysis Patients in China: A One-Year Follow-Up Study.

Recent studies have shown that coronavirus disease 2019 (COVID-19) aggravates anxiety in patients with maintenance hemodialysis (MHD), but it is still unclear how long this adverse effect will last. This study aims to investigate the impact of COVID-19 on the elevated anxiety symptoms of MHD patients 1 year after the outbreak. Assessment of elevated anxiety symptoms was performed on patients with MHD during early COVID-19 (February 17-February 29, 2020) and 1-year follow-up (March 1-March 13, 2021), and a total of 100 patients had completed face-to-face questionnaires at the first and 1-year follow-up. At the beginning of the outbreak, 40% of the patients with MHD had anxiety symptoms [self-rating anxiety scale (SAS) score ≥ 50], and 11% (SAS score: 60-69) and 2% (SAS score ≥ 70) of the patients had moderate and severe anxiety symptoms, respectively. Multivariate analysis shows that possibility of unaccompanied transfer, possibility of family members or themselves being infected in a hospital, added body temperature monitoring during dialysis, and increased medical procedures are the risk factors in elevated anxiety symptoms during early COVID-19. At the 1-year follow-up, the incidence of anxiety symptoms in the same group of patients declined to 28%, and all the patients had mild anxiety symptoms (SAS score: 50-59), which is significantly lower than that of the early COVID-19 pandemic with statistically significant difference (p = 0.003). Increased protective measures taken by the medical staves were the only risk factor in elevated anxiety symptoms during the 1-year follow-up. This study shows that COVID-19 has a direct impact on the deterioration of anxiety symptoms in patients with MHD. With the changes of the requirements for COVID-19 prevention and control, as well as the enhancement of propaganda and education of the pandemic and psychological care, the severity and risk factors of anxiety symptoms in the patients with MHD are changing. Thus, targeted interventions are suggested to improve the psychological endurance of the patients with MHD.

Efficacy of Apatinib plus S-1 Therapy in the Treatment of Advanced Gastric Cancer Patients and the Effect on the Levels of Tumor Markers and Th1 and Th2-Like Cytokines.

Objective: To assess the efficacy of apatinib plus S-1 therapy in the treatment of advanced gastric cancer patients and the effect on the levels of tumor markers and Th1 and Th2-like cytokines. Methods: From October 2019 to December 2020, 100 patients with advanced gastric cancer assessed for eligibility were recruited and assigned at a ratio of 1 : 1 to receive either S-1 regimen (tegafur, gimeracil, and oteracil potassium capsules) (observation group) or apatinib plus S-1 therapy (experimental group). Outcome measures included clinical efficacy serum tumor marker levels, Th1 and Th2-like cytokine levels, time to progression (TTP), overall survival (OS), and adverse events. Results: The S-1 therapy plus apatinib was associated with a significantly higher efficacy versus S-1 therapy alone (P < 0.05). The eligible patients given S-1 therapy plus apatinib showed significantly lower levels of serum carcinoembryonic antigen (CEA), glycoantigen 199 (CA199), and glycoantigen 125 (CA125) versus those receiving S-1 therapy (P < 0.05). S-1 therapy plus apatinib outperformed the single therapy of S-1 therapy in mitigating the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and interleukin-10 (IL-10) (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). S-1 therapy plus apatinib was associated with a significantly shorter TTP (5.2 ± 0.7 months) and a longer OS (9.3 ± 2.5 months) versus S-1 therapy alone (7.1 ± 1.3, 5.1 ± 1.3 months) (P < 0.05). Conclusion: The efficacy of apatinib plus S-1 therapy showed better improvement in lowering the serum tumor marker levels and ameliorating the Th1 and Th2-like cytokine levels versus S-1 therapy alone, so it is worthy of clinical application.

[Application of percutaneous transcalcaneal reconstruction technique for acute Achilles tendon insertion avulsion].

Objective: To introduce a percutaneous transcalcaneal reconstruction technique for the treatment of acute Achilles tendon insertion avulsion, and to assess its short-term effectiveness. Methods: Between January 2014 and June 2020, 25 patients with acute Achilles tendon insertion avulsion were treated with the percutaneous transcalcaneal reconstruction technique. There were 24 males and 1 female, with an average age of 44.1 years (range, 34-60 years). The disease duration was 1-5 days (mean, 1.8 days). There were 23 cases of sports injury and 2 cases of fall injury. The preoperative American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was 55.6±6.7 and the visual analogue scale (VAS) score was 4.6±0.5. The operation time, intraoperative blood loss, hospital stay, related complications, the time of weight-bearing standing with a slightly raised heel, and the time of walking with a slightly raised heel were recorded. The AOFAS ankle-hindfoot score and the VAS score were used to evaluate the ankle joint function and the pain. Achilles tendon continuity was examined by color Doppler ultrasonography and healing of the Achilles tendon was examined by MRI. At last follow-up, the Arner-Lindholm scale was used to evaluate the effectiveness. Results: The operation time was 45-50 minutes (mean, 46.8 minutes). The intraoperative blood loss was 10-20 mL (mean, 13.8 mL). The hospital stay was 4-6 days (mean, 4.9 days). The color Doppler ultrasonography before discharge showed the continuous recovery of the Achilles tendon. All incisions healed by first intention, and there was no complication such as sural nerve injury or deep venous thrombosis of lower extremity. All patients were followed up 15-50 months (mean, 30.3 months). After 14-21 days, the patients started to weight-bearing stand with a slightly raised heel, with an average of 17.6 days; they began to walk with a slightly raised heel at 20-28 days, with an average of 23.7 days. MRI showed that the Achilles tendon healed at last follow-up. The AOFAS score was 90.0±3.2 at 6 months after operation and 95.8±4.5 at last follow-up, and the VAS scores were 1.7±0.6 at 6 months and 1.0±0.8 at last follow-up, which were all improved when compared with those before operation (P<0.05); the difference was also significant between the two time points after operation (P<0.05). According to the Arner-Lindholm scale, the effectiveness at last follow-up was excellent in 25 cases. All patients had returned to sports. Conclusion: The percutaneous transcalcaneal reconstruction technique is a promising alternative option in treating acute Achilles tendon insertion avulsion, for it can achieve early rehabilitation and better ankle function recovery.

Association among sleep, depression, and health-related quality of life in patients with non-dialysis chronic kidney disease during the coronavirus disease 2019 pandemic.

BACKGROUND: Sleep disturbance is well documented as a crucial element that impairs health. Depression and health-related quality of life (HRQOL), which on behalf of a patient's overall perception of emotional, physical and social well-being, are increasingly emphasized self-reported health outcomes especially during the coronavirus disease 2019 (COVID-19) pandemic. Among dialysis patients, sleep disturbance is associated with depression and poorer HRQOL. The study was designed to depict the prevalence of sleep disturbance, and to explore the association among sleep, depression, and HRQOL in patients with non-dialysis chronic kidney disease (CKD) during the COVID-19 pandemic. METHODS: A total of 172 non-dialysis CKD patients enrolled in this cross-sectional study, with sociodemographic and clinical data recorded. Sleep, HRQOL, and depression were evaluated via the Pittsburgh Sleep Quality Index (PSQI), the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36), and the 9-item Patient Health Questionnaire (PHQ-9), respectively. RESULTS: A total of 100 (58%) met the criteria for poor sleep. Good sleepers had strikingly disparate HRQOL and depression scores compared to poor sleepers. Sleep disorders were significantly associated with decreased HRQOL and increased depression in regression models adjusted or unadjusted for sociodemographic and clinical characteristics. Mediation analysis indicated depression was a significant mediator explaining 51% of the relationship between sleep status with physical component summary (PCS) and played a fully mediating role in the association between sleep and mental component summary (MCS). CONCLUSIONS: Our study suggested the high incidence of sleep disorders in patients with non-dialysis CKD during the COVID-19 pandemic, as well as the tight associations among sleep, depression, and HRQOL. Considering the negative influences of sleep and depression on HRQOL, appropriate screening and treatment for these treatable health-related domains are necessary for patients with non-dialysis CKD.

Astragalus-Saffron-Rhubarb Mixture Delays the Progress of Diabetic Nephropathy in db/db Mice.

OBJECTIVE: This study aimed to investigate the protective effect of astragalus-saffron-rhubarb mixture (Bao'shen recipe, BSR) on diabetic nephropathy (DN) in db/db mice and preliminarily explore the possible underlying mechanism. METHODS: A total of 125 8-week-old male db/db mice with DN were randomly divided into five groups: model group, irbesartan group and high-, medium- and low doses of BSR group, while 25 male db/m mice were used as a blank control. At 8, 12, 16, 20, and 24 weeks of feeding, the animals were sacrificed and blood as well as urine samples were collected for blood glucose, urea nitrogen, creatinine and urinary albumin excretion rate (UAER) measurement via blood glucose meter or corresponding detection kits, respectively. The renal tissues of each mouse underwent hematoxylin and eosin (H&E), Masson, periodic acid Schiff (PAS) staining. Renal homogenate was used to detect IL-6, TNF-α, TNF-1R and TNF-2R by enzyme-linked immunosorbent assay. Additionally, the data obtained was statistically analyzed via one-way analysis of variance. RESULTS: BSR could effectively reduce the body weight, blood glucose, UAER, blood urea nitrogen and creatinine levels, relieve the proliferation of mesangial tissue, and lower the levels of IL-6, TNF-α, TNF-1R, and TNF-2R in renal tissue of db/db mice with DN. Of note, the high-dose BSR treatment group has advantages over irbesartan treatment group in improving above-mentioned aspects. CONCLUSION: BSR could effectively delay the progress of DN, partly related to its anti-inflammation effect.

Analysis of SO2 Physisorption by Edge-Functionalized Nanoporous Carbons Using Grand Canonical Monte Carlo Methods and Density Functional Theory: Implications for SO2 Removal.

Nanoporous carbons (NPCs) are ideal materials for the dry process of flue gas desulfurization (FGD) due to their rich pore structure and high specific surface area. To study the effect of edge-functionalized NPCs on the physisorption mechanism of sulfur dioxide, different functional groups were embedded at the edge of NPCs, and the physisorption behavior was simulated using the grand canonical Monte Carlo method (GCMC) combined with density functional theory (DFT). The results indicated that the insertion of acidic oxygenous groups or basic nitrogenous groups into NPCs could enhance the physisorption of SO2. The influence of edge functionalization on the pore structure of NPCs is also analyzed. To further explore the interaction in the adsorption process, the van der Waals (vdW) interaction and electrostatic interaction between the SO2 molecule and the basic structural unit (BSU) were investigated. Simulated results showed that edge functionalization had limited influence on vdW interaction and did not significantly change the distribution characteristics of vdW interaction. According to the study on electrostatic interaction, edge functionalization was found to promote inhomogeneity of the surface charge of the adsorbent, enhance the polarity of the adsorbent, and thus enhance the physisorption capacity of SO2. More importantly, we provide an idea for studying the difference in adsorption capacity caused by different functional groups connected to carbon adsorbents.

Neuroprotective Effects of Dexmedetomidine on the Ketamine-Induced Disruption of the Proliferation and Differentiation of Developing Neural Stem Cells in the Subventricular Zone.

Background: Ketamine disrupts the proliferation and differentiation of developing neural stem cells (NSCs). Therefore, the safe use of ketamine in pediatric anesthesia has been an issue of increasing concern among anesthesiologists and children's parents. Dexmedetomidine (DEX) is widely used in sedation as an antianxiety agent and for analgesia. DEX has recently been shown to provide neuroprotection against anesthetic-induced neurotoxicity in the developing brain. The aim of this in vivo study was to investigate whether DEX exerted neuroprotective effects on the proliferation and differentiation of NSCs in the subventricular zone (SVZ) following neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were equally divided into the following five groups: control group (n = 8), ketamine group (n = 8), 1 µg/kg DEX+ketamine group (n = 8), 5 µg/kg DEX+ketamine group (n = 8) and 10 µg/kg DEX+ketamine group (n = 8). Immediately after treatment, rats received a single intraperitoneal injection of BrdU, and the proliferation and differentiation of NSCs in the SVZ were assessed using immunostaining at 24 h after the BrdU injection. In the olfactory behavioral tests, rats in each group were raised until 2 months old, and the buried food test and olfactory memory test were performed. Results: The proliferation of NSCs and astrocytic differentiation in the SVZ were significantly inhibited at 24 h after repeated ketamine exposure in the neonatal period, and neuronal differentiation was markedly increased. Furthermore, pretreatment with moderately high (5 µg/kg) or high doses (10 µg/kg) of DEX reversed ketamine-induced disturbances in the proliferation and differentiation of NSCs. In the behavior tests, repeated neonatal ketamine exposure induced olfactory cognitive dysfunction in the adult stage, and moderately high and high doses of DEX reversed the olfactory cognitive dysfunction induced by ketamine. Conclusions: Based on the present findings, pretreatment with a moderately high (5 µg/kg) or high dose (10 µg/kg) of DEX may alleviate the developmental neurogenesis disorder in the SVZ at 24 h after repeated ketamine exposure and improve olfactory cognitive dysfunction in adulthood.

[Intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain].

OBJECTIVE: To observe the effect of intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain. METHODS: A total of 60 patients with moderate to severe cancer pain were randomly divided into an observation group and a control group，30 cases in each one. In the control group，opioids were taken to relief pain according to the three-step analgesic method of World Health Organization. On the base of the treatment as the control group, intradermal needling combined with heat-sensitive moxibustion were applied at Neiguan (PC 6), Hegu (LI 4), Zusanli (ST 36), Taichong (LR 3), etc. in the observation group, 14 days of treatment were required. The equivalent morphine consumption at the first day and whole course, the scores of cancer quality of life questionnaire-C30 (QLQ-C30) and Hamilton anxiety scale before and after treatment, and the adverse reaction rate were compared in the two groups. The total analgesic effective rate was evaluated. RESULTS: The total analgesic effective rate was 93.3% (28/30) in the observation group, higher than 73.3% (22/30) in the control group (P<0.05). The total equivalent morphine consumption in the observation group was less than the control group (P<0.05). After treatment, the QLQ-C30 scores were increased (P<0.001) and the HAMA scores were decreased (P<0.001) in the both groups, and those in the observation group were superior to the control group (P<0.001). The adverse reaction rates of fatigue, dizziness, nausea and vomiting, constipation in the observation group were lower than the control group (P<0.05). CONCLUSION: Intradermal needling combined with heat-sensitive moxibustion can reduce the dose of opioids, improve the quality of life, relief the anxiety in patients with moderate to severe cancer pain, and reduce the incidence of common adverse reaction of opioids.

Protein disulfide isomerase inhibits endoplasmic reticulum stress response and apoptosis via its oxidoreductase activity in colorectal cancer.

Protein disulfide isomerase (PDI), a principal endoplasmic reticulum resident oxidoreductase chaperone, is known to play a role in malignancies. This study aims to explore the molecular mechanism by which PDI regulates endoplasmic reticulum stress and the apoptosis signaling pathway in colorectal cancer (CRC). We determined the expression of PDI in CRC tissues and adjacent normal tissues. Gain- and loss- of function assays were conducted to evaluate the effects of PDI on oxidative stress, endoplasmic reticulum stress, and apoptosis in CRC cells, as reflected by hydrogen peroxide (H2O2) level and the expression of related proteins. PDI protein expression was upregulated in CRC tissues. Small molecule inhibitor of PDI or PDI knockdown reduced CRC cell viability and induced apoptosis. Overexpression of wild-type PDI augmented the viability of CRC cells and inhibited endoplasmic reticulum stress response and apoptosis. Small molecule inhibitor of PDI or PDI knockdown increased intracellular H2O2 level and activated apoptosis signaling pathway, which could be reversed by wild-type PDI restoration. Moreover, the catalytic active site of C-terminal of PDI was found to be indispensable for the regulatory effects of PDI on H2O2 levels, apoptosis and cell viability in CRC cells. Collectively, PDI inhibits endoplasmic reticulum stress and apoptosis of CRC cells through its oxidoreductase activity, thereby promoting the malignancy of CRC.

ErbB4 in Spinal PV Interneurons Regulates Mechanical Allodynia in Neuropathic Pain via Modulation of Glycinergic Inhibitory Tone.

BACKGROUND: Mechanical allodynia is the most common and challenging symptom associated with neuropathic pain; however, the underlying mechanisms are still unclear. The aim of this study was to investigate whether ErbB4, a receptor for neuregulin-1 (NRG1), participates in the modulation of mechanical allodynia. METHODS: Radiant heat and von Frey filaments were applied to assess nociceptive behaviors. Real-time quantitative polymerase chain reaction, Western blotting, immunofluorescence, and small interfering RNA were used to identify the likely mechanisms. RESULTS: ErbB4 was rapidly and persistently activated in spinal parvalbumin (PV) interneurons after chronic constriction injury (CCI) in mice. Knockdown of ErbB4 in the spinal cord prevented and reversed CCI-induced mechanical allodynia, and activation of ErbB4 by spinal application of NRG1 induced mechanical allodynia in naïve mice. Furthermore, we found that activation of ErbB4 decreased the glycine concentration in the spinal cord, contributing to modulation of mechanical allodynia. CONCLUSION: ErbB4 in spinal PV interneurons gates mechanical allodynia in neuropathic pain via regulation of glycinergic inhibitory tone, suggesting that a possible ErbB4-mediated process participates in the development of neuropathic pain.

Perioperative pulmonary aspiration and regurgitation without aspiration in adults: a retrospective observational study of 166,491 anesthesia records.

BACKGROUND: Pulmonary aspiration (PA) of gastric contents is a rare but serious perioperative complication. Recent studies focused on pediatric patients, but over a decade has passed since the latest incidence and outcome in adult population have been reported. Patients who experienced regurgitation without aspiration were rarely mentioned. Besides, our department proposed a modified rapid sequence induction (RSI) protocol in 2018 and its preventive effect remained to be examined. METHODS: A total of 166,491 anesthesia records from March 2015-October 2020 were reviewed. Outcomes from regurgitation events were classified as PA or regurgitation without aspiration following strict criteria. Available information including demographics, anesthetic managements, surgical procedures, and other medical records were reviewed for analysis. RESULTS: Among the 166,491 anesthesia records, 20 patients had PA (1:8,325), and 20 had regurgitation without aspiration (1:8,325). The morbidity of PA was 1:16,649, and the mortality was 1:55,497. During anesthesia induction, 76.0% of regurgitation events developed aspiration, and the remaining 24.0% had regurgitation without aspiration. But prior to anesthesia induction, only 10.0% regurgitation events developed aspiration. Emergency procedures were associated with serious risks of PA (OR: 27.1, 95% CI: 10.8-68.0) and regurgitation without aspiration (OR: 83.0, 95% CI: 24.3-283.1) compared with elective procedures. The highest incidence of pulmonary aspiration was observed in bronchoscopy procedures (2/1,747). The modified RSI reduced the incidence of regurgitation events during induction in emergency procedures but did not show significant advantages over classic protocol (0:1,055 versus 12:4,469, P=0.139) possibly due to insufficient sample size. The sample size required for future study was estimated based on the current data. CONCLUSIONS: The incidence of pulmonary aspiration and regurgitation without aspiration was low, especially in elective cases. Regurgitation during anesthesia induction had mostly developed aspiration. Further evaluation of the effect of modified RSI protocol needs a large sample size.

Exosomal miR-10b-5p mediates cell communication of gastric cancer cells and fibroblasts and facilitates cell proliferation.

Tumor microenvironment interacts with gastric cancer (GC) cells and affects tumor development. The communication between GC cells and fibroblasts has not been clearly studied and understood. MiR-10b-5p was found highly expressed in tissue and serum samples of patients with advanced stages (stage III+IV) than that in early stage patients (stage I+II). The expression determination of serum exosomal microRNA was also shown with high expression of miR-10b-5p in GC patients with advanced stages. Dual-luciferase activity assays indicated that miR-10b-5p targeted PTEN in GC cells and KLF11 in fibroblasts. The silence of miR-10b-5p up-regulated the expression of PTEN and repressed PI3K/Akt/mTORC1 signaling in GC cells. Clonogenic assay and MTT assay demonstrated that miR-10b-5p inhibitor could significantly reduce the colony formation and cell viability of GC cells. And the incubation of exosomal miR-10b-5p could increase the proliferation of GC cells. Immunohistochemistry staining revealed that high expression of α-SMA was detected in GC tissues with advanced stages. The overexpression of miR-10b-5p down-regulated KLF11 expression and elevated TGFßR1 expression in fibroblasts. In addition, miR-10b-5p inhibitor blocked the secretion of TGFß1 in GC cells and the directional migration of fibroblasts. Therefore, up-regulated exosomal miR-10b-5p is involved in the interaction of GC cells and fibroblasts in tumor microenvironment via participating in the regulation of TGFß signaling pathway.

Serum Cholesterol-Lowering Activity of ß-Sitosterol Laurate Is Attributed to the Reduction of Both Cholesterol Absorption and Bile Acids Reabsorption in Hamsters.

The research was performed to delineate how ß-sitosterol laurate (ß-SLE) consumption influenced serum and hepatic lipids. The results showed that 220 mg/5 mL oil/kg body weight of ß-SLE robustly reduced serum total triglyceride and cholesterol levels and the epididymal adipocyte size, and efficiently protected hepatic polyunsaturated fatty acids against lipid peroxidation through superoxide dismutase and glutathione transferase activity enhancement and malondialdehyde level reduction. Based on the changes of fecal cholesterol contents, fecal and hepatic bile acid (BAs) levels, and related protein expression, it was concluded that the mechanisms for lowering serum cholesterol by ß-SLE involved (i) the enhanced excretion of fecal cholesterol via down-regulation of intestinal Niemann-Pick C1-like 1 protein; (ii) the increased conversion from cholesterol to primary BAs via up-regulation of cholesterol-7α-hydroxylase and sterol 27-hydroxylase, which was induced by the reduced BAs reabsorption through up-regulating ileal apical sodium-dependent bile acid transporter and ileal bile acid-binding protein.