Dysrhythmic saliva microbiota in mobile phone addicts with sleep disorders and restored by acupuncture.

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

The regulation of intestinal flora on host's genes may play an essential role in the development of endometrial hyperplastic processes in yang deficiency individuals.

Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.

Mechanism of fibroblast growth factor 1 regulating fatty liver disorder in mule ducks.

Mule ducks tend to accumulate abundant fat in their livers via feeding, which leads to the formation of a fatty liver that is several times larger than a normal liver. However, the mechanism underlying fatty liver formation has not yet been elucidated. Fibroblast growth factor 1 (FGF1), a member of the FGF superfamily, is involved in cellular lipid metabolism and mitosis. This study aims to investigate the regulatory effect of FGF1 on lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells and elucidate the underlying molecular mechanism. Hepatocytes were induced by adding 1,500:750 µmol/L oleic and palmitic acid concentrations for 36 h, which were stimulated with FGF1 concentrations of 0, 10, 100, and 1000 ng/mL for 12 h. The results showed that FGF1 significantly reduced the hepatic lipid droplet deposition and triglyceride content induced by complex fatty acids; it also reduced oxidative stress; decreased reactive oxygen species fluorescence intensity and malondialdehyde content; upregulated the expression of antioxidant factors nuclear factor erythroid 2 related factor 2 (Nrf2), HO-1, and NQO-1; significantly enhanced liver cell activity; promoted cell cycle progression; inhibited cell apoptosis; upregulated cyclin-dependent kinase 1 (CDK1) and BCL-2 mRNA expression; and downregulated Bax and Caspase-3 expression. In addition, FGF1 promoted AMPK phosphorylation, activated the AMPK pathway, upregulated AMPK gene expression, and downregulated the expression of SREBP1 and ACC1 genes, thereby alleviating excessive fat accumulation in liver cells induced by complex fatty acids. In summary, FGF1 may alleviate lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells by activating the AMPK signaling pathway.

Inflammatory bowel disease and the associated risk of dry eye and ocular surface injury: a nationwide matched cohort study.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with lacrimal gland dysfunction and ocular inflammation. The objective of this research was to elucidate the temporal relationships between IBD, dry eye disease (DED), and corneal surface damage. METHODS: In a matched nationwide cohort study, we evaluated the risk of DED and corneal surface damage associated with IBD. Multivariable Cox proportional hazards regression analyses were implemented to estimate the risk of ocular complications. RESULTS: A total of 54,293 matched pairs were included for analyses. The median follow-up time was 8.3 years (interquartile range: 5.5 - 10.5). The period incidence of DED was 8.18 and 5.42 per 1000 person-years in the IBD and non-IBD groups, respectively. After adjusting for confounders, statistically significant associations were found between IBD and DED [adjusted hazard ratio (aHR): 1.43, 95% confidence interval (CI): 1.35 - 1.51, p < 0.0001], Sjögren's syndrome-related (aHR: 1.67, 95% CI:1.46 - 1.90, p < 0.0001) and non-Sjögren's syndrome-related subtypes (aHR: 1.38, 95% CI: 1.30 - 1.46, p < 0.0001). Furthermore, increased risks of corneal surface damage (aHR: 1.13, 95% CI: 1.03 - 1.24, p = 0.0094) among the patients with IBD were observed when compared with the controls. Other independent factors associated with corneal surface damage were age (aHR: 1.003), sex (male vs. female, aHR: 0.85), and monthly insurance premium (501-800 vs. 0-500 U.S. dollars, aHR: 1.45; ≥ 801 vs. 0-500 U.S. dollars, aHR: 1.32). CONCLUSIONS: Our results suggested that IBD was an independent risk factor for DED and ocular surface damage. Clinical strategies are needed to prevent visual impairment or losses in these susceptible patients.

Reliability of shear-wave elastography in assessing the stiffness of the nuchal fascia and the thickness of upper cervical muscles.

OBJECTIVE: To determine the reliability of shear-wave elastography (SWE)in assessing the stiffness of the nuchal fascia and the thickness of upper cervical muscles in neutral head posture (NHP) or forward head posture (FHP). METHODS: Sixteen healthy adults (mean age: 21.69 ± 1.01years, 9 females) were included. SWE mode was chosen to measure the nuchal fascia shear modulus and muscle thickness was measured in B-mode. Measurements were collected by two independent investigators on two different days. The intraclass correlation coefficient (ICC) was used to measure the relative reliability, and the standard error of measurement (SEM) were used to measure the absolute reliability. RESULTS: Intra­rater (ICC = 0.63-0.89) and inter-rater (ICC = 00.54-0.82) reliability for the nuchal fascia shear modulus were moderate to excellent. Intra­rater (ICC = 00.64-0.96) and inter-rater (ICC = 00.48-0.86) reliability for upper cervical muscles thickness were moderate to excellent. The SEM percentage oscillated from 3.27% to 13.55%. There were significant differences(P < 0.05) between NHP and FHP on nuchal fascia shear modulus, right side splenius capitis muscle thickness and left side semispinalis capitis muscle thickness, but no significant differences(P > 0.05) were observed between the right and left sides. The upper cervical muscles thickness of males was significantly thicker(P < 0.01) than females while no significant differences were observed (P > 0.05) on the nuchal fascia shear modulus. CONCLUSIONS: Ultrasound-based SWE may be a reliable tool for assessing the stiffness of the nuchal fascia and the thickness of upper cervical muscles in clinical practice. REGISTRATION NUMBER: ChiCTR2200055736.

Diphtheria toxin activates ribotoxic stress and NLRP1 inflammasome-driven pyroptosis.

The ZAKα-driven ribotoxic stress response (RSR) is activated by ribosome stalling and/or collisions. Recent work demonstrates that RSR also plays a role in innate immunity by activating the human NLRP1 inflammasome. Here, we report that ZAKα and NLRP1 sense bacterial exotoxins that target ribosome elongation factors. One such toxin, diphtheria toxin (DT), the causative agent for human diphtheria, triggers RSR-dependent inflammasome activation in primary human keratinocytes. This process requires iron-mediated DT production in the bacteria, as well as diphthamide synthesis and ZAKα/p38-driven NLRP1 phosphorylation in host cells. NLRP1 deletion abrogates IL-1ß and IL-18 secretion by DT-intoxicated keratinocytes, while ZAKα deletion or inhibition additionally limits both pyroptotic and inflammasome-independent non-pyroptotic cell death. Consequently, pharmacologic inhibition of ZAKα is more effective than caspase-1 inhibition at protecting the epidermal barrier in a 3D skin model of cutaneous diphtheria. In summary, these findings implicate ZAKα-driven RSR and the NLRP1 inflammasome in antibacterial immunity and might explain certain aspects of diphtheria pathogenesis.

Efficacy and safety of ilioinguinal neurectomy in open tension-free inguinal hernia repair: A meta-analysis of randomized controlled trials.

BACKGROUND: There is still controversy surrounding routine ilioinguinal neurectomy in open tension-free inguinal hernia repair. METHOD: PubMed, Cochrane Library and EMBASE databases were searched for randomized controlled trials of ilioinguinal neurectomy in open tension-free inguinal hernia repair. Revman 5.3 software was used for meta-analysis. RESULT: Meta-analysis revealed that the incidence of severe pain on the first postoperative day was lower in the ilioinguinal neurectomy group (ING) than in the ilioinguinal nerve preservation group (INPG) [P < 0.0001]. The incidence of no pain in the first month postoperatively [P = 0.0004], the incidence of no pain in the sixth months postoperatively [P < 0.00001], and the numbness incidence in the first month postoperatively [P = 0.001] in the ING was higher than that in the INPG. There was no significant difference in the incidence of severe pain in the first month postoperatively [P = 0.20], the numbness incidence in the sixth postoperative month [P = 0.05], the hypoesthesia incidence in the first [P = 0.15] and sixth [P = 0.85] postoperative months between the two groups. CONCLUSION: Ilioinguinal neurectomy in open tension-free inguinal hernia repair can better prevent postoperative pain.

The Association between Autoimmune Thyroid Disease and Ocular Surface Damage: A Retrospective Population-Based Cohort Study.

Autoimmune thyroid diseases (ATDs) are potentially connected to lacrimal gland dysfunction and ocular surface disruption. This study aimed to evaluate the relationships between ATD, dry eye disease (DED), and corneal surface damage. In a matched nationwide cohort study, we used Taiwan's National Health Insurance research database to compare the incidences of DED and corneal surface damage between subjects with and without ATD. Multivariable Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the ophthalmological outcomes. A total of 50,251 matched pairs with 748,961 person-years of follow-up were included for analysis. The incidence of DED was 16.37 and 8.36 per 1000 person-years in the ATD and non-ATD groups, respectively. ATDs were significantly associated with increased DED (aHR: 1.81, 95% CI: 1.73-1.89, p < 0.0001). This association was generally consistent across the subgroups of age, sex, different comorbidity levels, and use of systemic corticosteroids or not. Furthermore, patients with ATD had a higher risk of corneal surface damage compared with non-ATD subjects (aHR: 1.31, 95% CI: 1.19-1.44, p < 0.0001), including recurrent corneal erosions (aHR: 2.00, 95% CI: 1.66-2.41, p < 0.0001) and corneal scars (aHR: 1.26, 95% CI: 1.01-1.59, p = 0.0432). Other independent factors for corneal surface damage were age, sex, diabetes mellitus, Charlson Comorbidity Index scores, and use of systemic corticosteroids. Our results suggested that ATDs were associated with higher risks of DED and corneal surface damage. Considering the high prevalence of ATD, prophylactic and therapeutic strategies should be further developed to prevent irreversible vision loss in this susceptible population.

Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression.

BACKGROUND: Corosolic acid is a pentacyclic triterpene acid with hypoglycemic, anti-inflammatory, and anti-cancer effects. However, its potential targets in hepatocellular carcinoma (HCC) are unknown, hindering clinical utilization. METHODS: Differentially expressed proteins of the Bel-7404 cell line were identified with tandem mass tag analysis and differentially expressed genes (DEGs) of an HCC TCGA dataset using bioinformatics. Gene functions and pathways were inferred using the DAVID database. Online databases were used to establish P4HA2 expression in HCC (GEPIA2) and its relationship with patient survival (UALCAN and The Human Protein Atlas), the association between P4HA2 expression and immune cell infiltration (TIMER2), and DNA methylation of the P4HA2 gene (MethSurv). Cell proliferation, cell cycle, and cell death were assessed with PI and SYTOX-Green staining, CCK-8, and colony formation assays. Protein expression levels were detected by Western blotting. RESULTS: A total of 44 differentially expressed proteins and 4498 DEGs were identified. Four genes whose proteins were also found in the differential protein profile but with opposing expressions were selected as candidate targets. The candidate gene prolyl 4-hydroxylase subunit alpha 2 (P4HA2) was recognized as the only potential target due to its high expression in public datasets, association with poor patient survival, and relation to immune cell infiltration in HCC tissues. Moreover, the DNA methylation status in 4 CpG islands of the P4HA2 gene correlated with a poor prognosis. Furthermore, corosolic acid treatment inhibited the proliferation of HCC cell lines Bel-7404 and HepG2 in a dose-dependent manner, caused G2/M phase cell cycle arrest, and promoted cell death. In addition, the treatment reduced P4HA2 protein levels. CONCLUSION: Our results indicate that P4HA2 is a potential target of corosolic acid. Thus, they contribute to understanding molecular changes in HCC after corosolic acid treatment and facilitate finding new treatment regimens.

Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement.

To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.

Novel function of a putative TaCOBL ortholog associated with cold response.

The plant COBRA protein family plays an important role in secondary cell wall biosynthesis and the orientation of cell expansion. The COBRA gene family has been well studied in Arabidopsis thaliana, maize, rice, etc., but no systematic studies were conducted in wheat. In this study, the full-length sequence of TaCOBLs was obtained by homology cloning from wheat, and a conserved motif analysis confirmed that TaCOBLs belonged to the COBRA protein family. qRT-PCR results showed that the TaCOBL transcripts were induced by abiotic stresses, including cold, drought, salinity, and abscisic acid (ABA). Two haplotypes of TaCOBL-5B (Hap5B-a and Hap5B-b), harboring one indel (----/TATA) in the 5' flanking region (- 550 bp), were found on chromosome 5BS. A co-dominant marker, Ta5BF/Ta5BR, was developed based on the polymorphism of the two TaCOBL-5B haplotypes. Significant correlations between the two TaCOBL-5B haplotypes and cold resistance were observed under four environmental conditions. Hap5B-a, a favored haplotype acquired during wheat polyploidization, may positively contribute to enhanced cold resistance in wheat. Based on the promoter activity analysis, the Hap5B-a promoter containing a TATA-box was more active than that of Hap5B-b without the TATA-box under low temperature. Our study provides valuable information indicating that the TaCOBL genes are associated with cold response in wheat.

Acupuncture ameliorates Mobile Phone Addiction with sleep disorders and restores salivary metabolites rhythm.

Objectives: Mobile Phone Addiction (MPA) is a novel behavioral addiction resulting in circadian rhythm disorders that severely affect mental and physical health. The purpose of this study is to detect rhythmic salivary metabolites in MPA with sleep disorder (MPASD) subjects and investigate the effects of acupuncture. Methods: Six MPASD patients and six healthy controls among the volunteers were enrolled by MPA Tendency Scale (MPATS) and Pittsburgh Sleep Quality Index (PSQI), then the salivary samples of MPASD and healthy controls were collected every 4-h for three consecutive days. Acupuncture was administered for 7 days to MPASD subjects, then saliva samples were collected again. Salivary metabolomes were analyzed with the method of LC-MS. Result: According to our investigation, 70 (57.85%) MPA patients and 56 (46.28%) MPASD patients were identified among 121 volunteers. The symptoms of the 6 MPASD subjects were significantly alleviated after acupuncture intervention. The number of rhythmic saliva metabolites dropped sharply in MPASD subjects and restored after acupuncture. Representative rhythmic saliva metabolites including melatonin, 2'-deoxyuridine, thymidine, thymidine 3',5'-cyclic monophosphate lost rhythm and restored after acupuncture, which may attribute to promising MPASD treatment and diagnosis biomarkers. The rhythmic saliva metabolites of healthy controls were mainly enriched in neuroactive ligand-receptor interaction, whereas polyketide sugar unit biosynthesis was mainly enriched in MPASD patients. Conclusion: This study revealed circadian rhythm characteristics of salivary metabolites in MPASD and that acupuncture could ameliorate MPASD by restoring part of the dysrhythmia salivary metabolites.

Systemic Lupus Erythematosus and Risk of Dry Eye Disease and Corneal Surface Damage: A Population-Based Cohort Study.

Systemic lupus erythematosus (SLE) potentially involves multiple parts of the ocular system, including the lacrimal glands and the cornea. The present study sought to assess the risk of aqueous-deficient dry eye disease (DED) and corneal surface damage in patients with SLE. We conducted a population-based cohort study using Taiwan's National Health Insurance research database to compare the risks of DED and corneal surface damage between subjects with and without SLE. Proportional hazard regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the study outcomes. The propensity score matching procedure generated 5083 matched pairs with 78,817 person-years of follow-up for analyses. The incidence of DED was 31.90 and 7.66 per 1000 person-years in patients with and without SLE, respectively. After adjusting for covariates, SLE was significantly associated with DED (aHR: 3.30, 95% CI: 2.88-3.78, p < 0.0001) and secondary Sjögren's syndrome (aHR: 9.03, 95% CI: 6.86-11.88, p < 0.0001). Subgroup analyses demonstrated that the increased risk of DED was augmented among patients with age < 65 years and female sex. In addition, patients with SLE had a higher risk of corneal surface damage (aHR: 1.81, 95% CI: 1.35-2.41, p < 0.0001) compared to control subjects, including recurrent corneal erosion (aHR: 2.98, 95% CI: 1.63-5.46, p = 0.0004) and corneal scar (aHR: 2.23, 95% CI: 1.08-4.61, p = 0.0302). In this 12-year nationwide cohort study, we found that SLE was associated with increased risks of DED and corneal surface damage. Regular ophthalmology surveillance should be considered to prevent sight-threatening sequelae among patients with SLE.

Increased Risk of Suicide Attempt in Patients with Alopecia Areata: A Nationwide Population-Based Cohort Study.

BACKGROUND: There is growing evidence that patients with alopecia areata (AA) have an increased risk of developing psychiatric comorbidities. However, the relationship between AA and suicidal behaviors remains unclear. OBJECTIVE: The objective of this study was to investigate the association between AA and suicidal behaviors. METHODS: Participants were recruited from the National Health Insurance Research Database in Taiwan, including 10,515 patients with AA and 10,5150 matched controls, to assess the risk of suicide attempts. A Cox regression model was used for all analyses. RESULTS: Compared with the controls, an increased risk of suicide attempts was observed in patients with AA, with an adjusted hazard ratio of 6.28 (95% confidence interval, 4.47-8.81). Suicide risk remained significantly elevated in AA patients when stratified by underlying psychiatric disorders. The mean age of initial suicidal behaviors was also lower in patients with AA. CONCLUSIONS: Patients with AA had a significantly higher incidence of suicidal attempts than controls, regardless of concurrent psychiatric illness. Further studies are needed to elucidate the pathophysiology of the association between AA and suicidality. In addition, dermatologists should be aware of the increased suicidality of patients with AA.

Rheumatoid Arthritis Associated with Dry Eye Disease and Corneal Surface Damage: A Nationwide Matched Cohort Study.

Rheumatoid arthritis is potentially connected to ocular disorders, such as corneal inflammation and lacrimal gland destruction. This study aimed to evaluate the risk of dry eye disease (DED) and corneal surface damage among patients with rheumatoid arthritis. In a nationwide cohort study, we utilized Taiwan's National Health Insurance research database and conducted propensity score matching to compare the risks of DED and corneal surface damage between patients with and without rheumatoid arthritis. Proportional hazards regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the outcomes of interest. The matching procedure generated 33,398 matched pairs with 501,377 person-years of follow-up for analyses. The incidence of DED was 23.14 and 10.25 per 1000 person-years in patients with and without rheumatoid arthritis, respectively. After adjusting for covariates, rheumatoid arthritis was significantly associated with DED (aHR: 2.03, 95% CI: 1.93−2.13, p < 0.0001). The association was generally consistent across the subgroups of age, sex, use of systemic corticosteroids, and different comorbidity levels. In addition, patients with rheumatoid arthritis had a higher risk of corneal surface damage (aHR: 1.36, 95% CI: 1.21−1.51, p < 0.0001) compared to control subjects. Other independent factors for corneal surface damage were age and sleeping disorders. Rheumatoid arthritis was associated with an increased risk of DED and corneal surface damage. Ophthalmological surveillance is required to prevent vision-threatening complications in this susceptible population.

Dupilumab in the treatment of genodermatosis: A systematic review.

Dupilumab interferes with the signaling pathways of IL-4 and IL-13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome, epidermolysis bullosa pruriginosa, and hyper-IgE syndrome, are Th2 skewed diseases with activation of type 2 inflammation. We performed this systematic review to investigate the therapeutic role of dupilumab in the treatment of genodermatosis. A systematic search was conducted of the PubMed, Embase, Web of Science, and Cochrane databases from inception to December 13, 2021. The review included studies with relevant terms including "dupilumab," "genodermatosis", "Netherton syndrome", "ichthyosis", "epidermolysis bullosa" and "hyper-IgE syndrome". The initial search yielded 2,888 results, of which 28 studies and 37 patients with genodermatosis were enrolled. The assessed genodermatoses included Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with genetic disorders. Most of the reported cases showed significant clinical improvement after the initiation of dupilumab treatment without major adverse events. Decreased immunoglobulin E levels and cytokine normalization have also been documented. In conclusion, Dupilumab may have a potential therapeutic role in certain genodermatoses skewed towards T helper 2 (Th2) immunity, including Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with some genetic disorders.

Effects of repetitive peripheral magnetic stimulation on spasticity evaluated with modified Ashworth scale/Ashworth scale in patients with spastic paralysis: A systematic review and meta-analysis.

Background: Spasticity is a common motor disorder resulting from upper motor neuron lesions. It has a serious influence on an individual's motor function and daily activity. Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive and painless approach developed for therapeutic intervention in clinical rehabilitation. However, the effectiveness of this intervention on spasticity in patients with spastic paralysis remains uncertain. Objective: This study aimed to investigate the effectiveness of rPMS on spasticity, motor function, and activities of daily living in individuals with spastic paralysis. Methods: PubMed, PEDro, Embase, Cochrane Library, and Web of Science were searched for eligible papers with date up to March 31, 2022. Two independent researchers conducted study screening, data extraction, and methodological quality assessment. RCTs that explored the effects of rPMS on spasticity, motor function, and activities of daily living in patients with spastic paralysis were included for review. The Cochrane collaboration tool was used to assess methodological quality. The cumulative effects of available data were processed for a meta-analysis using Reedman software. Results: Eight studies with 297 participants were included. Most of the studies presented low to moderate risk of bias. Compared with the control group, the results showed that rPMS had a significant effect on spasticity (all spasticity outcomes: standardized mean difference [SMD] = -0.55, 95% confidence interval [CI]: -0.94 to -0.16, I 2 = 40%, and P = 0.006, Modified Ashworth Scale: mean difference [MD] = -0.48, 95% CI: -0.82 to -0.14, I 2 = 0%, and P = 0.006), motor function (Fugl-Meyer Assessment: MD = 4.17, 95% CI: 0.89 to 7.46, I 2 = 28%, and P = 0.01), and activities of daily living (Barthel Index: MD = 5.12, 95% CI: 2.58 to 7.67, I 2 = 0%, and P < 0.0001). No side effect was reported. Conclusion: The meta-analysis demonstrated that the evidence supported rPMS in improving spasticity especially for passive muscle properties evaluated with Modified Ashworth Scale/Ashworth Scale, as well as motor function and daily activity of living in individuals with spastic paralysis. Study registration: The reviewed protocol of this study is registered in the international prospective register of systematic reviews (PROSPERO) (CRD42022322395). Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022322395.

Ethylene Activates the EIN2-EIN3/EIL1 Signaling Pathway in Tapetum and Disturbs Anther Development in Arabidopsis.

Ethylene was previously reported to repress stamen development in both cucumber and Arabidopsis. Here, we performed a detailed analysis of the effect of ethylene on anther development. After ethylene treatment, stamens but not pistils display obvious developmental defects which lead to sterility. Both tapetum and microspores (or microsporocytes) degenerated after ethylene treatment. In ein2-1 and ein3-1 eil1-1 mutants, ethylene treatment did not affect their fertility, indicating the effects of ethylene on anther development are mediated by EIN2 and EIN3/EIL1 in vivo. The transcription of EIN2 and EIN3 are activated by ethylene in the tapetum layer. However, ectopic expression of EIN3 in tapetum did not induce significant anther defects, implying that the expression of EIN3 are regulated post transcriptional level. Consistently, ethylene treatment induced the accumulation of EIN3 in the tapetal cells. Thus, ethylene not only activates the transcription of EIN2 and EIN3, but also stabilizes of EIN3 in the tapetum to disturb its development. The expression of several ethylene related genes was significantly increased, and the expression of the five key transcription factors required for tapetum development was decreased after ethylene treatment. Our results thus point out that ethylene inhibits anther development through the EIN2-EIN3/EIL1 signaling pathway. The activation of this signaling pathway in anther wall, especially in the tapetum, induces the degeneration of the tapetum and leads to pollen abortion.

The Association between General Anesthesia and New Postoperative Uses of Sedative-Hypnotics: A Nationwide Matched Cohort Study.

Sedative−hypnotic misuse is associated with psychiatric diseases and overdose deaths. It remains uncertain whether types of anesthesia affect the occurrence of new postoperative uses of sedative−hypnotics (NPUSH). We used reimbursement claims data of Taiwan's National Health Insurance and conducted propensity score matching to compare the risk of NPUSH between general and neuraxial anesthesia among surgical patients who had no prescription of oral sedative−hypnotics or diagnosis of sleep disorders within the 12 months before surgery. The primary outcome was NPUSH within 180 days after surgery. Multivariable logistic regression models were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 92,222 patients were evaluated after matching. Among them, 15,016 (16.3%) had NPUSH, and 2183 (4.7%) were made a concomitant diagnosis of sleep disorders. General anesthesia was significantly associated both with NPUSH (aOR: 1.17, 95% CI: 1.13−1.22, p < 0.0001) and NPUSH with sleep disorders (aOR: 1.11, 95% CI: 1.02−1.21, p = 0.0212) compared with neuraxial anesthesia. General anesthesia was also linked to NPUSH that occurred 90−180 days after surgery (aOR: 1.12, 95% CI: 1.06−1.19, p = 0.0002). Other risk factors for NPUSH were older age, female, lower insurance premium, orthopedic surgery, specific coexisting diseases (e.g., anxiety disorder), concurrent medications (e.g., systemic steroids), postoperative complications, perioperative blood transfusions, and admission to an intensive care unit. Patients undergoing general anesthesia had an increased risk of NPUSH compared with neuraxial anesthesia. This finding may provide an implication in risk stratification and prevention for sedative−hypnotic dependence after surgery.