Locus coeruleus tyrosine hydroxylase positive neurons mediated the peripheral and central therapeutic effects of transcutaneous auricular vagus nerve stimulation (taVNS) in MRL/lpr mice.

OBJECTIVE: This study aims to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the development of systemic lupus erythematosus (SLE) in MRL/lpr mice. METHODS: MRL/lpr mice were treated with taVNS for ten weeks. Locus coeruleus (LC) tyrosine hydroxylase positive (TH+) neurons were selectively lesioned by stereotactic injection of 6-hydroxydopamine (6-OHDA) or selectively activated by chemogenetic methods. Sympathetic denervation was conducted by intraperitoneal injection of 6-OHDA. RESULTS: TaVNS activated the TH + neurons in LC. TaVNS produced central therapeutic effects by reducing the number of hippocampal microglia, and increasing the number of surviving LC TH+ neurons in MRL/lpr mice. TaVNS also retarded the development of lymphadenectasis and splenomegaly, decreased the proportion of double-negative T (DNT) cells, and alleviated nephritis in MRL/lpr mice. The lesion of LC TH+ neurons eliminated both these central and peripheral therapeutic effects of taVNS, while chemogenetic activation of LC TH+ neurons mimicked most central and peripheral protective effects of taVNS in MRL/lpr mice. Furthermore, taVNS regulated the autonomic nervous system in MRL/lpr mice. CONCLUSION: This study provides direct evidence that taVNS can retard the development of peripheral and central symptoms of SLE, which is mediated by the LC TH+ neurons.

Tripterygium wilfordii Hook F combination therapy with methotrexate for rheumatoid arthritis: An updated meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory arthropathy. Tripterygium wilfordii Hook F (TwHF) is common herbal medicine for the treatment of RA in China. However, many important issues, such as efficacy, safety and optimal doses of the combination therapy of TwHF and Methotrexate (MTX) for RA remain to be evaluated. AIMS OF THE STUDY: This study aims to evaluate the efficacy and safety of combination therapy of TwHF and MTX for RA by meta-analysis of randomized clinical trials (RCTs). MATERIAL AND METHODS: Relevant literature was searched from English (PubMed, Web of Science, EMBASE, and Cochrane library) and Chinese databases (WanFang, VIP, CNKI) until December 2021. Response rates and rates of adverse events (AEs) were independently extracted and analyzed. RESULTS: Fourteen randomized controlled trials (RCTs) were included with a total of 1446 patients, which included eight new RCTs with a total of 803 new patients when compared with the previous meta-analysis (Wang et al., 2017). Compared to MTX monotherapy, TwHF + MTX was revealed a higher effective rate (RR = 1.15, 95% CI: 1.10, 1.21), partial remission rate (RR = 1.27, 95% CI: 1.15, 1.40) and remission rate (RR = 1.31, 95% CI: 1.11, 1.55). The addition of TwHF benefited the clinical symptoms (such as tender joint count) and most laboratory indexes (such as the tumor necrosis factor-α). According to the subgroup analyses, the efficacy of the TwHF + MTX seems to be positively associated with the dose of TwHF (10 mg/d vs 30-60 mg/d), negatively related to the dose of MTX (∼10 mg/w vs ∼15 mg/w) and methodological risk of bias of included RCTs, and unrelated to the duration of therapy (12-week vs 24-week). For safety, the addition of TwHF did not increase the risk of most AEs and even reduced the risk of infection and liver AEs. CONCLUSION: Combining TwHF with MTX may be a superior strategy in the treatment of RA compared with MTX monotherapy. The optimal combination of TwHF + MTX therapy might be TwHF at 30-60 mg/d with MTX (∼10 mg/w). Further high-quality double-blind RCTs may be able to change the conclusions of our study, which are still warranted.

Efficacy and safety of traditional Chinese medicine for the treatment of epilepsy: A updated meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of epilepsy. METHODS: A comprehensive search of the database in both Chinese and English was performed. Data from the selected studies were extracted and analyzed independently by two authors. RESULTS: 30 randomized controlled trials (RCTs) were included in the meta-analysis with a total of 2471 patients. Among them, 4 trials (n = 235) focused on TCM monotherapy, while the other 26 trials (n = 2236) assessed the benefit of TCM as an add-on therapy to antiseizure medications (ASMs). For the efficacy, the meta-analysis found (1) The effective rate in TCM monotherapy group was higher than that in control group (OR = 4.92, 95 % CI: 2.29-10.57, Z = 4.08, P 0.0001); (2) The add-on of TCM also increased the effective rate (OR = 3.37, 95 % CI: 2.65-4.30, Z = 9.85, P 0.00001) and seizure freedom rate (OR = 1.93, 95 % CI: 1.53-2.44, Z = 5.58, P 0.00001). In terms of safety, the add-on of TCM reduced the rate of total adverse events (OR = 0.46, 95 % CI: 0.31-0.67, Z = 3.96, P 0.0001) as well as adverse events of the gastrointestinal and nervous system. 26 different TCM prescriptions were used in these included RCTs. Among them, the 5 most frequently used herbs were Acorus tatarinowii (19 out of 26), Glycyrrhiza uralensis (13 out of 26), Gastrodia elata (12 out of 26), Pinellia ternata (11 out of 26) and Poria cocos (11 out of 26). CONCLUSION: This study suggested that TCM may be a relatively efficacious and safe clinical strategy for the treatment of epilepsy. Several limitations still exist, such as the risk of bias in the included studies, the diversified composition of TCM prescriptions, and the relatively low quality of study design.

The hidden inequality: the disparities in the quality of daily use masks associated with family economic status.

Wearing high-quality masks plays a critical role in reducing COVID-19 transmission. However, no study has investigated socioeconomic inequality in the quality of masks. Addressing this gap, this paper explored the relationships between mask's quality and family economic status. The cross-sectional survey was conducted in two Chinese universities by distributing structured questionnaires to assess participants' characteristics including family economic status, and meanwhile collecting their masks to evaluate the quality by measuring particle filtration efficiency. The valid responses were obtained from 912 students with mean age of 19.556 ± 1.453 years and were analyzed by using fractional or binary logistic regression. Three main findings were presented. First, inequality existed in the quality of masks. 36.07% of students were using unqualified masks with average filtration efficiency of 0.795 ± 0.119, which was much lower than China's national standard (0.9). Of those masks with identified production date, 11.43% were manufactured during COVID-19 outbreak when market was flooded with counterfeit production, and thus were of poor quality with average filtration efficiency of 0.819 ± 0.152. Second, better family economic status was associated with better masks' filtration efficiency and greater probability of using qualified masks. Third, students with better family economic status tend to use masks with individual packaging, and unique patterns and special designs, which may lead to inequality on a psychological level. Our analysis reveals the hidden socioeconomic inequality that exist behind cheap masks. In facing the challenges of future emerging infectious diseases, it is important to address the inequity to ensure equal access to affordable qualified personal protection equipment.

Metabolic profiles in plasma of patients with herpes labialis based on GC-MS.

OBJECTIVE: This study aims to compare the plasma metabolic profiles of patients with herpes labialis with healthy controls and identify the biomarkers of herpes labialis. SUBJECTS AND METHODS: We collected 18 patients with herpes labialis and 20 healthy individuals. Plasma samples from both groups were analyzed using gas chromatography-mass spectrometry (GC-MS). RESULTS: According to the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), we found that metabolic profiles had changed in patients with herpes labialis compared to the controls. By further selecting the different metabolites according to the variable importance in the projection (VIP) and p valve of t-tests, we found that acetic acid, pyroglutamic acid, alanine, ethanedioic acid, cyclohexaneacetic acid, pyruvic acid, d-mannose, phosphoric acid, l-amphetamine, and citric acid were decreased in patients with herpes labialis, while sedoheptulose and ethylamine were increased. Pathway analysis showed that herpes labialis may affect the amino acid and energy metabolism. CONCLUSIONS: Our findings may contribute to elucidating the metabolic basis of herpes labialis and provide a new perspective for further research on the "Shang-Huo" state in traditional Chinese medicine (TCM).

Azithromycin pretreatment exacerbates atopic dermatitis in trimellitic anhydride-induced model mice accompanied by correlated changes in the gut microbiota and serum cytokines.

Atopic dermatitis (AD) is a common inflammatory skin disease. This study aims to investigate the effect of azithromycin (AZI) pretreatment, a common macrolide-type antibiotic, on the trimellitic anhydride (TMA) induced AD-like symptoms in mice. AZI (25 mg/kg, once daily, 5 days) was administered intragastrically before the 10-day TMA challenge. AD-like symptoms were assessed by ear thickening, scratching behavior, and pathological or immunofluorescence staining; Cytokines in the skin tissue and serum were measured by cytometric bead array; and the compositions of gut microbiota were assessed by 16S rRNA gene sequencing. AZI pretreatment accelerated the development of ear thickening and enhanced the severity of developed AD-like symptoms. AZI pretreatment promoted the infiltrations of neutrophil-like cells, T cells, and mast cells in ear skin. AZI pretreatment elevated the levels of IL-4, IL-6, and IL-17A in the ear skin of AD model mice, but it increased serum TNF-α and IL-6. AZI-pretreatment increased four gut bacterial genera (Bacteroides, Candidatus_Saccharibacteria_unclassified, Acetatifactor, Firmicutes_unclassified) but depleted three short-chain fatty acids producing gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). AD-associated symptoms were positively associated with skin IL-4 and IL-17A, serum TNF-α, and IL-6, and Acetatifactor, but they negatively correlated to the three decreased gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). Thus, our results demonstrate that AZI exposure deteriorates TMA-induced AD-like symptoms in mice, which is related to the imbalances of gut microbiota and skin/serum cytokines.

Organocatalytic aza-Michael/retro-aza-Michael reaction: pronounced chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction.

A detailed experimental investigation of an aza-Michael reaction of aniline and chalcone is presented. A series of Cinchona alkaloid-derived organocatalysts with different functional groups were prepared and used in the aza-Michael and retro-aza-Michael reaction. There was an interesting finding that a complete reversal of stereoselectivity when a benzoyl group was introduced to the cinchonine and cinchonidine. The chirality amplification vs. time proceeds in the quinine-derived organocatalyst containing silicon-based bulky group, QN-TBS, -catalyzed aza-Michael reaction under solvent-free conditions. In addition, we have demonstrated for the first time that racemization was occurred in suitable solvents under mild conditions due to retro-aza-Michael reaction of the Michael adduct of aniline with chalcone. These indicate the equilibrium of retro-aza-Michael reaction and aza-Michael reaction produce the happening of chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction under different conditions, which would be beneficial to the development of novel chiral catalysts for the aza-Michael reactions.

Organocatalytic Michael addition of 1,3-dicarbonyl indane compounds to nitrostyrenes.

To map out the efficient organocatalyst requirements in the Michael addition of 1,3-dicarbonyl indane compounds to nitrostyrenes, a dozen different amino organocatalysts containing a p-toluenesulfonyl group (Ts) have been evaluated; excellent enantio-selectivities (up to er 92:8) were obtained with a primary amine-based Ts-DPEN catalyst and a plausible catalytic reaction mechanism was proposed on the basis of the experimental results.

Fabrication of Transparent UV-Cured Coatings with Allyl-Terminated Hyperbranched Polycarbosilanes and Thiol Silicone Resins.

To improve thermal stability and hardness of UV-cured materials, a series of UV-cured solvent-free coatings were prepared from allyl-terminated hyperbranched polycarbosilanes and thiol silicone resins. The silicone coatings prepared have pencil hardness of 4-9 H, water absorption no more than 0.04 wt %, and transmittance higher than 94%. The temperature for the coatings' starting thermal decomposition is higher than 236 °C; especially, that of the coating prepared with G1 is as high as 371.1 °C. The UV-cured coatings in this work exhibit much higher pencil hardness than and superior thermal stability to those reported previously.