Elevated TRPV2 expression in the facial nerve of rats by cold stimulation: Implications for Bell's palsy.

OBJECTIVE: Bell's palsy, also referred to as clinical manifestations of unilateral facial nerve palsy, encompasses downward angling of the corners of the mouth, the absence of forehead creases, and unilateral incomplete eyelid closure. The incidence of Bell's palsy has increased progressively in recent years, but the underlying mechanism of its occurrence remains unknown; therefore, it is essential to investigate both the cause and treatment of Bell's palsy. Member 2 of the Subfamily V Transient Receptor Potential Cation Channel is a mechanically and thermally sensitive ion channel that plays a crucial role in neural growth and development. Using a novel modeling technique, we endeavored to develop an animal model of Bell's palsy and determine whether TRPV2 expression is altered throughout the course of a facial nerve injury. MATERIALS AND METHODS: The rats were categorized into 3 groups, and their facial nerve function was assessed using RT-qPCR, WB, and pathologic testing, respectively, after undergoing unilateral cold air stimulation for 1, 3, and 7 days. TRPV2 expression was identified using these techniques. RESULTS: In response to cold stimulation, rats exhibited facial nerve paralysis symptoms, demyelinating lesions in the facial nerve, and increased TRPV2 expression. CONCLUSIONS: Extended cold stimulation of the facial nerve in rats may lead to an imbalance in facial nerve homeostasis and increased TRPV2 expression. These findings will contribute to the understanding of the potential mechanism by which cold stimulation affects the facial nerve. Moreover, this finding implies that TRPV2 could possibly function as an additional diagnostic marker or therapeutic target in the context of Bell's palsy.

Influence of cold-stimulated adipocyte supernatant on the expression of adhesion-related molecules in Schwann cell line.

Bell's palsy is the most common form of facial nerve palsy. This study aimed to explore the pathogenesis of Bell's palsy by investigating the effect of cold-stimulated adipocyte supernatant on adhesion molecule expression in Schwann cell line. Schwann cells were cultured in regular or adipocyte-conditioned medium and analyzed using RNA sequencing. The mRNA expression of Schwann cell adhesion molecules melanoma cell adhesion molecule (MCAM), protocadherin 9 (PCDH9), and intercellular cell adhesion molecule 1 (ICAM1) was determined using real-time reverse-transcription polymerase chain reaction. Differentially expressed genes were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted. Compared with Schwann cells in 37 °C, the expression of MCAM, PCDH9, and ICAM1 was downregulated in Schwann cells treated with cold-stimulated adipocyte supernatant compared with Schwann cells in 37 °C. Adipocytes subjected to cold exposure may weaken the adhesion capacity of Schwann cells and disrupt the local homeostasis of Schwann cell-axon interactions by affecting the expression of MCAM, PCDH9, and ICAM1, ultimately leading to the development of demyelinating lesions.

Bell's palsy was associated with TRPV2 downregulation of Schwann cell by cold stress.

OBJECTIVE: Epidemiological and clinical studies have shown that sharp changes in the ambient temperature are associated with the occurrence and development of Bell's palsy. However, the specific pathogenesis of peripheral facial paralysis remains nebulous. This study investigated the effect of cold stress on transient receptor potential cation channel subfamily V member 2 (TRPV2) secretion by Schwann cells and its role in Bell's palsy. MATERIALS AND METHODS: Schwann cell morphology was observed using transmission electron microscopy (TEM). Cell proliferation, apoptosis and cell cycle were analysed using CCK8 and flow cytometry. ELISA, Reverse transcription-quantitative PCR, western blotting and immunocytochemical fluorescence staining were used to detect the effects of cold stress on TRPV2, neural cell adhesion molecule (NCAM) and nerve growth factor (NGF) expression in Schwann cells. RESULTS: Cold stress resulted in a widening of the intercellular space, and the particles on the membrane showed different degrees of loss. Cold stress may cause Schwann cells to enter a cold dormant state. ELISA, RT-qPCR, western blotting and immunocytochemical fluorescences staining indicated that cold stress inhibited the expression of TRPV2, NCAM, and NGF. CONCLUSIONS: Drastic temperature difference between cold and heat can downregulate TRPV2 and the secretome of Schwann cells. The imbalance of Schwann cell homeostasis under such stress may contribute to nerve signalling dysfunction leading to the development of facial paralysis.

Serum uric acid is not associated with major depressive disorder in European and South American populations: a meta-analysis and two-sample bidirectional Mendelian Randomization study.

OBJECTIVE: Although previous epidemiological studies have demonstrated that serum uric acid (SUA) is associated with major depressive disorder (MDD), these analyses are prone to biases. Here, we applied the Mendelian Randomization approach to determine whether SUA is causally associated with MDD. METHODS: We conducted a meta-analysis to evaluate the relationship between SUA and MDD, then applied summary data from the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium to estimate their causal effect using a two-sample bidirectional Mendelian Randomization (MR) analysis. Thereafter, the causal effect was further researched using genetic risk scores (GRS) as instrumental variables (IVs). RESULTS: Results of a meta-analysis of articles comprising 6975 and 13,589 MDD patients and controls, respectively, revealed that SUA was associated with MDD (SMD = -0.690, 95% CI: -0.930 to -0.440, I2 = 97.4%, P < 0.001). In addition, the five MR methods revealed no causal relationship existed between SUA and MDD, which corroborated the results obtained via the GRS approach. CONCLUSION: This paper found little evidence that this association between SUA and MDD is casual. Genetically, there was no significant causal association between SUA and MDD.

The role of age at menarche and age at menopause in Alzheimer's disease: evidence from a bidirectional mendelian randomization study.

The association between endogenous estrogen exposure and Alzheimer's disease (AD) remains inconclusive in previous observational studies, and few Mendelian randomization (MR) studies have focused on their causality thus far. We performed a bidirectional MR study to clarify the causality and causal direction of age at menarche and age at menopause, which are indicators of endogenous estrogen exposure, on AD risk. We obtained all genetic datasets for the MR analyses using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. The MR analyses indicated no significant causal relationship between the genetically determined age at menarche (outlier-adjusted inverse variance weighted odds ratio [IVWOR] = 0.926; 95% confidence interval [CI], 0.803-1.066) or age at menopause (outlier-adjusted IVWOR = 0.981; 95% CI, 0.941-1.022) and AD risk. Similarly, AD did not show any causal association with age at menarche or age at menopause. The sensitivity analyses yielded similar results. In contrast, an inverse association was detected between age at menarche and body mass index (BMI, outlier-adjusted IVW ß = -0.043; 95% CI, -0.077 to -0.009). Our bidirectional MR study provides no evidence for a causal relationship between the genetically determined age at menarche or age at menopause and AD susceptibility, or vice versa. However, earlier menarche might be associated with higher adult BMI.

Adiponectin affects estimated glomerular filtration rate: A two-sample bidirectional Mendelian randomization study.

BACKGROUND: The causal relationship between adiponectin (ADPN) and estimated glomerular filtration rate (eGFR) is unclear. This study adopts a two-sample bidirectional Mendelian randomization (MR) study to explore the causal relationship between ADPN and eGFR. METHODS: Using eight single nucleotide polymorphisms (SNP) of ADPN and 26 SNP of eGFR as instrumental variables, the study performs a two-sample bidirectional MR study using MR inverse-variance weighted (IVW), MR-Egger and weighted median approach to evaluate the causal relationship between ADPN and eGFR. Using the genetic risk score (GRS) of ADPN and eGFR as instrumental variables, the study performs a second MR analysis to assess the association between ADPN and eGFR. RESULTS: In ADPN to eGFR MR analysis, the IVW, weighted median and GRS analysis all showed that ADPN had a causal effect on eGFR after removing potential confounders of the ADPN-eGFR relation (IVW: ß = .016, P = .002; weighted median: ß = .012, P = .022; GRS: ß = .016, P = 1.48E-05). As both ADPN and eGFR were natural log-transformed in the corresponding GWAS, eGFR increased by 0.15% for any 10% increase in ADPN. In eGFR to ADPN MR analysis, eGFR had no causal effect on ADPN after removing potential confounders of the eGFR-ADPN relation (All P values > 0.05). The heterogeneity test and sensitivity analysis indicated some heterogeneity, but no directional pleiotropy. CONCLUSION: Adiponectin has a causal effect on eGFR, while eGFR has no causal effect on ADPN. ADPN may be a clinical target for improving eGFR and treating chronic kidney disease caused by decreased eGFR.

Effects of Adiponectin on T2DM and Glucose Homeostasis: A Mendelian Randomization Study.

PURPOSE: The associations of adiponectin with type 2 diabetes mellitus (T2DM), glucose homeostasis (including ß-cell function index (HOMA-ß), insulin resistance (HOMA-IR), fasting insulin (FI) and fasting glucose (FG)) have reported in epidemiological studies. However, the previous observational studies are prone to biases, such as reverse causation and residual confounding factors. Herein, a Mendelian Randomization (MR) study was conducted to determine whether causal effects exist among them. MATERIALS AND AND METHODS: Two-sample MR analyses and multiple sensitivity analyses were performed using the summary data from the ADIPOGen consortium, MAGIC Consortium, and a meta-analysis of GWAS with a considerable sample of T2DM (62,892 cases and 596,424 controls of European ancestry). We got eight valid genetic variants to predict the causal effect among adiponectin and T2DM and glucose homeostasis after excluding the probable invalid or pleiotropic variants. RESULTS: Adiponectin was not associated with T2DM (odds ratio (OR) = 1.004; 95% confidence interval (CI): 0.740, 1.363) when using MR Egger after removing the invalid SNPs, and the results were consistent when using the other four methods. Similar results existed among adiponectin and HOMA-ß, HOMA-IR, FI, FG. CONCLUSION: Our MR study revealed that adiponectin had no causal effect on T2DM and glucose homeostasis and that the associations among them in observational studies may be due to confounding factors.

Assessment Causality in Associations Between Serum Uric Acid and Risk of Schizophrenia: A Two-Sample Bidirectional Mendelian Randomization Study.

PURPOSE: Although increasing lines of evidence showed associations between serum uric acid (UA) levels and schizophrenia, the causality and the direction of the associations remain uncertain. Thus, we aimed to assess whether the relationships between serum UA levels and schizophrenia are causal and to determine the direction of the association. PATIENTS AND METHODS: Two-sample bidirectional Mendelian randomization (MR) analyses and various sensitivity analyses were performed utilizing the summary data from genome-wide association studies within the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium. Secondary MR analyses in both directions were conducted within summary data using genetic risk scores (GRSs) as instrumental variables. RESULTS: Three MR methods provided no causal relationship between serum UA and schizophrenia. Furthermore, GRS approach showed similar results in the three MR methods after adjustment for heterogeneity. By contrast, inverse variance weighted method, weighted median and GRS approach suggested a causal effect of schizophrenia risk on serum UA after adjustment for heterogeneity (per 10-symmetric percentage increase in schizophrenia risk, beta: -0.039, standard error (SE): 0.013, P = 0.003; beta: -0.036, SE: 0.018, P = 0.043; beta: -0.039, SE: 0.013, P = 0.002; respectively). Moreover, in both directions' analyses, the heterogeneity and sensitivity tests suggested no strong evidence of bias due to pleiotropy. CONCLUSION: Schizophrenia may causally affect serum UA levels, whereas the causal role of serum UA concentrations in schizophrenia was not supported by our MR analyses. These findings suggest that UA may be a useful potential biomarker for monitoring treatment or diagnosis of schizophrenia rather than a therapeutic target for schizophrenia.

Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury.

OBJECTIVE: Inflammation and immune responses are crucial factors associated with the onset and progression of stroke. Interleukin-11 (IL-11) is a hematopoietic IL-6 family cytokine that functions as an anti-inflammatory agent against various inflammatory diseases. However, its roles in stroke remain unknown. In this study, we investigated the effects of IL-11 on cerebral ischemia-reperfusion injury in a model of focal cerebral ischemia. METHODS: Mice were randomly divided into five groups the vehicle group, the middle cerebral artery occlusion (MCAO) group, the MCAO plus adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C group, the MCAO plus IL-11 treatment group, and the MCAO plus IL-11 treatment and compound C group. Focal cerebral ischemia was induced by occluding the left middle cerebral artery, and reperfusion was achieved by withdrawing the suture 2 h after ischemia. The protein expression levels of IL-11 were measured using Western blot analysis, and its location was detected using immunohistochemistry and immunofluorescence staining. The infarct volume was examined using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the neurobehavioral progression was assessed using the neurological scoring system. The expression of astrocytes and microglia was detected using immunochemistry, and real-time quantitative PCR was used for the gene quantification of inflammatory cytokines. The extent of cerebral ischemia-reperfusion injury was tested using Nissl staining and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of the apoptotic proteins Bax, Bcl-2 and cleaved caspase-3 were detected using Western blot analysis, and the oxidative stress was also measured. RESULTS: The expression of IL-11 mRNA and protein significantly decreased after cerebral ischemia. Immunohistochemical staining showed a large amount of IL-11 in the cerebral cortex of the mice in the vehicle group, whereas the immunoreactivity of IL-11 remained weak for 24 h in the MCAO group. Immunofluorescent staining further confirmed that IL-11 was mainly expressed in the neurons. It was suggested that IL-11 (20 µg/kg) treatment ameliorated infarction and reduced neurological scores. In addition, IL-11 proved to reduce neuropathic damage, glial activation, and the expression of proinflammatory cytokines and increase the expression of anti-inflammatory cytokines after cerebral ischemia. IL-11 was also able to alleviate oxidative stress caused by cerebral ischemia, and AMPK inhibition enhanced the alleviation. Moreover, IL-11 was found to inhibit apoptosis caused by cerebral ischemia, which could also be facilitated by AMPK inhibitors. SIGNIFICANCE: Our research suggests that IL-11 is decreased during cerebral ischemia-reperfusion injury, but IL-11 treatment can improve neurological function and reduce the cerebral infarct volume, which can trigger stroke in mice. AMPK inhibition can further promote the protective effect of IL-11 in stroke. Overall, we demonstrate that IL-11 is of therapeutic interest in controlling stroke and managing cerebral ischemia-reperfusion injury.

[Comparative study on curative effects of stroke treated with acupuncture by NIRS].

OBJECTIVE: To compare the intracephalic imaging differences of stroke treated with combined therapy of scalp and body acupuncture and body acupuncture only, in order to apply the image basis for the differences of clinical curative effects. METHODS: Twenty cases of stroke were randomized into a body acupuncture group (group A) and a scalp and body acupuncture group (group B), ten cases in each group respectively. In group A, body acupuncture was applied simply, and different acupoints were selected according to the symptoms: Shousanli (LI 10), Jianliao (TE 14), Huantiao (GB 30) and Jiaji (EX-B 2) etc. were selected for hemiplegia, Fengchi (GB 20), Xiaguan (ST 7) and Quanliao (SI 18) etc. were for facial paralysis, Fengfu (GV 16) and Lianquan (CV 23) etc. were for aphasia. In group B, combined therapy were applied, the body acupoints selection was same as above; for scalp acupoints, corresponding motor area, sensory area and foot motor sensory area were selected. Instant changes of local cerebral blood flow before and after treatment were examined and evaluated by NIRS and the curative effects of both groups were evaluated. RESULTS: The total therapeutic effective rate was 90.0% (9/10) and the basically cured rate was 30.0% (3/10) in group A; and 100.0% (10/10) and 50.0% (5/10) respectively in group B, indicating that the clinical curative effect in group B was superior to that in group A at 20, 30 min of acupuncture treatment (P < 0.05). Both imaging results showed that blood flows of prefrontal cortex in both groups were increased with varying degrees after treatment (P < 0.05, P < 0.01); the cerebral blood flow in group B was much more improved than that in group A at 20, 30 min of acupuncture treatment (all P < 0.05). CONCLUSION: Acupuncture can significantly increase blood flow and oxygen saturation in brain cortex, and the effect with combined therapy of scalp and body acupuncture is superior to that with body acupuncture.

[Effects of electric-moxibustion on brain mantle accessed with near-infrared imaging].

OBJECTIVE: To observe the influence of electric-moxibustion at Baihui (GV 20) or Shenque (CV 8) on the cerebral blood flow. METHODS: Twenty healthy volunteer were treated by electric-moxibustion at Baihui (GV 20) or Shenque (CV 8) with multi-functional electric-moxibustion instrument. The changes of the forehead cortex blood flow during moxibustion were detected by dynamic continuous spectrum near-infrared imaging. RESULTS: There were significant differences as the forehead cortex blood flow after electric-moxibustion at Baihui (GV 20) for 20 and 30 minutes compared with their initial data (P < 0.05, P < 0.01); and as the forehead cortex blood flow after electric-moxibustion at Shenque (CV 8) for 10, 20 and 30 minutes compared with their initial data (P<0. 05, P<0. 01). CONCLUSION: Electric-moxibustion at both Baihui (GV 20) and Shenque (CV 8) can improve the volume of brain cortex blood flow and electric-moxibustion at Shenque (CV 8) has rapid effect.

A green process to prepare chromic oxide green pigment.

A hydrogen reduction and activated sintering process was proposed to prepare chromic oxide green pigment. Through ICP, XRD, SEM, FT-IR, UV, and CIE-L*a*b* colorimetric analysis, key factors and mechanism that influenced preparation of chromic oxide green pigment were studied. The results revealed that lower hydrogen reduction temperature, suitable addition of Al and Ba, were beneficial to obtaining the high quality chromic oxide green pigment. Typically, when the hydrogen reduction temperature was kept at 450-500 degrees C, physicochemical properties and color performance of the prepared chromic oxide green pigment doped with about 0.1-0.2 wt % Al and 0.2-0.5 wt % Ba conformed to commercial pigment standards. Additionally, characteristics of the green process were discussed. About 90 wt % KOH was reused directly and about 90 wt % Cr(VI) was conversed to Cr(III) directly from potassium chromate to chromic oxide green pigment. Integrating the proprietary green metallurgical process from chromite ore to potassium chromate of this laboratory, more than 99 wt % Cr(VI) could be conversed to Cr(III) compounds and about 99 wt % KOH could be recycled to use. The whole green process, ranging from chromite ore to chromic oxide green pigment, eventually not only provided the possibility for producing the high quality chromic oxide green pigment, but could reach comprehensive utilization of resources, inner recycle of KOH, and zero emission of Cr(VI).

[Replacement of third-generation cephalosporins by piperacillin-tazobactam decreases colonization of extended-spectrum beta-lactamases-producing intestinal Escherichia coli].

OBJECTIVE: To investigate the role of replacement of third-generation cephalosporins by piperacillin-tazobactam (pip-tazo) in influencing the colonization of extended-spectrum beta-lactamases (ESBLs)-producing Escherichia coli (E. coli) in intestinal tract. METHODS: The study was divided into two phases lasting altogether 9 months, namely the pre-replacement phase (phase I, 3 months) and replacement phase (phase II, 6 months). In the latter phase, third-generation cephalosporins was restricted and replaced by pip-tazo. In phase I and phase IIb (the last 3 months of phase II), clinical data and rectal swab were taken for E. coli isolation as follow: within 24 hrs after admission (baseline screening), every week and 48 hrs before discharge. ESBLs production was detected with double disc test. Acquisition rate of ESBLs-producing E. coli were calculated both in ES1 group (patients' rectal swab collected and tests at least 2 times) and ES2 group (ES1 but with negative ESBLs either at the time of screening on admission or at anytime during the hospital stay). Continuous variable was compared using unpaired t-test and categorical variables was compared using Pearson Chi square test. Fisher's exact test was used in the two phases. RESULTS: In phase IIb, as compared with in phase I, the total consumption of antibiotics other than pip-tazo was reduced by 38.40%, the third-generation cephalosporins consumption was reduced by 70.11%, but pip-tazo consumption was raised by 895.35%. Meanwhile, the acquisition rate of ESBLs-producing E. coli in rectal swab was significantly decreased in phase IIb as compared with phase I (11.4% vs 24.0%) in ES1 group and the same is true in ES2 group (11.8% vs 27.9%). CONCLUSION: Replacement of third-generation cephalosporin with pip-tazo can reduce colonization of ESBLs--producing E. coli in intestinal tract.

[Application of FTIR and XPS technique to the analysis of the mixture containing chromium in a low valence state].

Chromium has various valence states and in the process of preparing chromium oxides with low valence state of chromium, chromium compounds with different valence state of chromium can usually be produced as intermediates. Due to the difference in property of these intermediates, they always have remarkable influences on the morphological characteristics of the final product. The composition of the intermediate was very complicated in the process of synthesizing chromium oxide with low valence state of chromium by reducing potassium chromate with hydrogen. To explore the reaction mechanism and further optimize the technical process, the composition of the intermediate obtained from the reduction of K2CrO4 with hydrogen was investigated through the combination of XPS, FTIR and XRD. The XPS results revealed that the intermediate of reducing potassium chromate with hydrogen is trivalent chromium compound; the results of FTIR and XRD indicated that the intermediate mainly consists of Cr(OH)3 x nH2O, HCrO2 and a little amount of KOH or KCrO2. On the basis of the above analysis of the intermediate, the possible reactions that occurred in the reduction process were suggested.

[Clinical observation on combined acupuncture and moxibustion therapy for treatment of 160 cases of polyneuritis].

OBJECTIVE: To observe clinical therapeutic effect of combined acupuncture and moxibustion therapy on polyneuritis. METHODS: One hundred and sixty cases were treated with combined scalp acupuncture, body acupuncture (stimulating root of nerve as main), cupping and pricking at segmental root of nerve, and electric hot moxibustion, and their therapeutic effects were observed. RESULTS: One hundred and thirty-eight cases were cured (86.3%) and the total effective rate was 100.0%. The average recovery time for clinical symptoms was 12.81 days, the average recovery time for nervous system signs was 19.76 days, the average recovery time for recovery of ocular muscular dyskinesia was 15.14 days. There was significant therapeutic effect for improvement of simple symptoms, with significant differences when the first and second therapeutic courses compared with that before treatment (P < 0.01). CONCLUSION: The combined acupuncture and moxibustion therapy has a definite therapeutic effect on polyneuritis.