Case Report: Upper Thoracic Esophageal Paralysis Accompanying a Type 1 Leprosy Reaction.

Type 1 leprosy reactions (T1LRs) occur mainly in patients with borderline leprosy and an unstable immune status. The main symptoms of T1LRs include aggravated skin lesions and nerve damage. Nerve damage involving the glossopharyngeal and vagus nerves causes dysfunction of the nose, pharynx, larynx, and even the esophagus, which are innervated by these nerves. Here, we report a case of upper thoracic esophageal paralysis caused by vagus nerve involvement in a patient with T1LRs. Although infrequent, this serious emergency merits attention.

Psoriasis complicated with metabolic disorder is associated with traditional Chinese medicine syndrome types: a hospital-based retrospective case-control study.

OBJECTIVE: To explore the distribution law of traditional Chinese medicine (TCM) syndrome types in patients with psoriasis vulgaris complicated by metabolic disorders based on the same pathogenic factors as blood-heat and blood-stasis in the pathogenesis of psoriasis and metabolic disorders and to further analyze the correlation between adiponectin and the distribution law. METHODS: From 1 January 2018 to 31 December 2019, patients diagnosed with psoriasis in the inpatient or outpatient department of Dermatology Ward of Shanghai Yueyang Hospital and normal participants who underwent physical examination in the physical examination center over the same period were retrospectively reviewed. Demographic data, medical history, metabolic disorder indices, and TCM syndrome indices of psoriasis patients and healthy volunteers were evaluated. RESULTS: We included 307 patients with psoriasis and 613 healthy controls. On analyzing past medical history, the proportion of overweight and obesity and the comorbidity of diabetes in the psoriasis group (53.42 and 14.66%) were significantly higher than in the control group (43.88 and 7.67%, respectively; p < .05). The abnormal rates of triglyceride (34.20%), high-density lipoprotein cholesterol (50.49%), and HbA1c (18.57%) levels in the psoriasis group were higher than those in the normal control group (26.75, 17.13, and 12.56%, respectively). Overall, the incidence of metabolic disorders in psoriasis patients (267/307, 86.97%) was higher than that in the normal controls (484/613, 78.96%). Among the different syndrome types, the blood-stasis group had significantly higher rates of hypertension, diabetes, and abnormal glycosylated hemoglobin (46.07, 19.10, and 24.72%, respectively) than those of the control group (27.57, 7.67, and 12.56%; p < .05). Patients with blood stasis syndrome had the highest metabolic disorder comorbidity rate (93.26%) and lowest adiponectin level (p < .05). CONCLUSIONS: TCM syndrome differentiation of psoriasis, especially the diagnosis of blood-stasis syndrome, prompts the early screening of patients with metabolic comorbidities. For patients with psoriasis with metabolic disorder, TCM for promoting blood circulation and removing blood stasis can be compatibly applied without contraindications. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (Trial ID: NCT03942185).

A Desaturative Approach for Aromatic Aldehyde Synthesis via Synergistic Enamine, Photoredox and Cobalt Triple Catalysis.

Aromatic aldehydes are fundamental intermediates that are widely utilised for the synthesis of important materials across the broad spectrum of chemical industries. Accessing highly substituted derivatives can often be difficult as their functionalizations are generally performed via electrophilic aromatic substitution, SE Ar. Here we provide an alternative and mechanistically distinct approach whereby aromatic aldehydes are assembled from saturated precursors via a desaturative process. This novel strategy harnesses the high-fidelity of Diels-Alder cycloadditions to quickly construct multi-substituted cyclohexenecarbaldehyde cores which undergo desaturation via the synergistic interplay of enamine, photoredox and cobalt triple catalysis.

Merging Halogen-Atom Transfer (XAT) and Cobalt Catalysis to Override E2-Selectivity in the Elimination of Alkyl Halides: A Mild Route toward contra-Thermodynamic Olefins.

We report here a mechanistically distinct tactic to carry E2-type eliminations on alkyl halides. This strategy exploits the interplay of α-aminoalkyl radical-mediated halogen-atom transfer (XAT) with desaturative cobalt catalysis. The methodology is high-yielding, tolerates many functionalities, and was used to access industrially relevant materials. In contrast to thermal E2 eliminations where unsymmetrical substrates give regioisomeric mixtures, this approach enables, by fine-tuning of the electronic and steric properties of the cobalt catalyst, to obtain high olefin positional selectivity. This unprecedented mechanistic feature has allowed access to contra-thermodynamic olefins, elusive by E2 eliminations.

Electrochemical Synthesis of Benzimidazoles via Dehydrogenative Cyclization of Amidines.

The development of efficient and sustainable methodologies for the synthesis of N-heterocycles is a constant focus of organic synthesis. Herein an electrochemical method is reported for the synthesis of benzimidazoles through dehydrogenative cyclization of easily available N-aryl amidines. The reactions were conducted under simple constant current conditions in an undivided cell without need for catalysts, chemical oxidants, or additives, and produced H2 as the only theoretical byproduct.

Minimization of Back-Electron Transfer Enables the Elusive sp3 C-H Functionalization of Secondary Anilines.

Anilines are some of the most used class of substrates for application in photoinduced electron transfer. N,N-Dialkyl-derivatives enable radical generation α to the N-atom by oxidation followed by deprotonation. This approach is however elusive to monosubstituted anilines owing to fast back-electron transfer (BET). Here we demonstrate that BET can be minimised by using photoredox catalysis in the presence of an exogenous alkylamine. This approach synergistically aids aniline SET oxidation and then accelerates the following deprotonation. In this way, the generation of α-anilinoalkyl radicals is now possible and these species can be used in a general sense to achieve divergent sp3 C-H functionalization.

A New Therapy for Vitiligo Using Fire Needles: A Systematic Review of Evidence from 3618 Subjects.

INTRODUCTION: Fire needle therapy has been reported as an effective treatment for vitiligo. However, current clinical evidence has not been systematically evaluated. The aim of this study was to determine whether fire needle therapy is effective and safe for treating vitiligo. METHODS: Seven databases were searched until October 2019 for randomized controlled trials on fire needle therapy, with and without conventional treatments, versus any type of conventional therapy for treating vitiligo. The RevMan 5.3.5 software was used to perform meta-analysis of the included studies. RESULTS: Forty-seven trials comprising 3618 patients were included. Fire needle combined with conventional vitiligo treatments had a higher efficacy (risk ratio (RR): 1.55, 95% confidence interval (CI): 1.46-1.65, P < 0.00001 and RR: 1.41, 95% CI: 1.24-1.61, P < 0.00001, respectively) and a greater effect on restoring the color of the area of the skin lesion (mean difference (MD): 3.40, 95% CI: 2.11-4.69, P < 0.00001), increasing the pigment point of vitiligo (MD: 0.83, 95% CI: 0.54-1.13, P < 0.00001) and improving the cytokine level (MD: 8.10, 95% CI: 6.94-9.27, P < 0.00001) and effectual time (MD: -4.76, 95% CI: -7.33 to -2.19, P=0.0003) than traditional methods. Limb lesions (RR: 1.60, 95% CI: 1.31-1.95, P < 0.00001) were more effectively treated when the treatments included fire needles, whereas the therapeutic effect of fire needles on either the head and neck (RR: 1.13, 95% CI: 0.78-1.64, P=0.52) or torso lesions (RR: 1.22, 95% CI: 0.82-1.81, P=0.33) was not significantly different compared to that without fire needles. No statistically significant differences in adverse effects (RR: 1.15, 95% CI: 0.89-1.49, P=0.28) and recurrence rates (RR: 0.90, 95% CI: 0.17-4.92, P=0.91) during the follow-up period were observed between treatment with and without fire needles. CONCLUSIONS: Fire needle therapy combined with other conventional treatments is useful in treating vitiligo. Further studies with larger sample sizes should be performed to make a conclusive judgment. This trial is registered with CRD42018094918.

Site-selective electrooxidation of methylarenes to aromatic acetals.

Aldehyde is one of most synthetically versatile functional groups and can participate in numerous chemical transformations. While a variety of simple aromatic aldehydes are commercially available, those with a more complex substitution pattern are often difficult to obtain. Benzylic oxygenation of methylarenes is a highly attractive method for aldehyde synthesis as the starting materials are easy to obtain and handle. However, regioselective oxidation of functionalized methylarenes, especially those that contain heterocyclic moieties, to aromatic aldehydes remains a significant challenge. Here we show an efficient electrochemical method that achieves site-selective electrooxidation of methyl benzoheterocycles to aromatic acetals without using chemical oxidants or transition-metal catalysts. The acetals can be converted to the corresponding aldehydes through hydrolysis in one-pot or in a separate step. The synthetic utility of our method is highlighted by its application to the efficient preparation of the antihypertensive drug telmisartan.

Efficacy of fish oil and its components in the management of psoriasis: a systematic review of 18 randomized controlled trials.

CONTEXT: Fish oil and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have anti-inflammatory properties, but their effect on psoriasis and its comorbidities remains inconclusive. OBJECTIVE: The aim of this quantitative systematic review was to evaluate the efficacy and safety of fish oil and its components in the treatment of psoriasis and its comorbidities. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang databases were searched from inception to March 30, 2019. STUDY SELECTION: Randomized controlled trials were eligible for inclusion if they measured the effect of fish oil and its components in the treatment of patients with psoriasis. DATA EXTRACTION: Eighteen randomized controlled trials involving 927 study participants were included. RESULTS: Monotherapy with fish oil or ω-3 PUFAs had no effect on the Psoriasis Area and Severity Index (PASI) score (P = 0.47), lesion area (P = 0.34), or pruritus (P = 0.62). Fish oil or ω-3 PUFAs combined with conventional treatments, however, resulted in a decreased PASI score (mean difference [MD], -3.92; 95%CI, -6.15 to -1.69; P = 0.0006) and lesion area (MD, -30.00; 95%CI, -33.82 to -26.18; P < 0.0001). Safety evaluation suggested no between-group differences. Fish oil and its components reduced certain risk factors for obesity, cardiovascular disease, and metabolic disease in patients with psoriasis and also regulated several inflammatory mediators. CONCLUSIONS: Overall, when combined with conventional treatments, fish oil and its components may have beneficial effects on psoriasis and its comorbidities, including obesity, cardiovascular disease, and metabolic disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019128631.

Establishment of Mouse Models of Psoriasis with Blood Stasis Syndrome Complicated with Glucose and Lipid Metabolism Disorders.

BACKGROUND: Psoriasis has been reported as a high-risk factor for quality of life and survival rate in patients with metabolic disorder. However, there is no animal model for studying this disease. This study aimed to establish and evaluate mouse models of psoriasis with blood stasis syndrome (which is a key to psoriasis pathogenesis, according to Chinese Medicine) complicated with metabolic disorders. METHOD: Forty-five C57BL/6 mice were randomly divided into the blank control (Control), psoriasis (Imiquimod (IMQ)), psoriasis with metabolic disorders (IMQ + streptozotocin (STZ)), psoriasis with blood stasis syndrome (BSS) (IMQ + BSS), and psoriasis with blood stasis syndrome complicated with metabolic disorders (IMQ + STZ + BSS) groups (n = 9 mice/group). Psoriasis lesions were induced using IMQ cream (on both the ears and back, except in the Control group). Mice of the IMQ + BSS group were fed a half-fat, high-sugar diet and stimulated with ice-water swimming every day. Mice of the IMQ + STZ group were fed a half-fat, high-sugar diet and injected with STZ. Mice of the IMQ + STZ + BSS group were subjected to the same treatments as the IMQ + STZ and IMQ + BSS groups. After induction, the mice in each group were observed for vital signs, ear thickness, body weight, and psoriasis area and severity index (PASI) score. The mice were fasted for 12 h before determination of related laboratory serum indexes. Dorsal skin lesions, aortic arch pathology sections, and signal transducer and activator of transcription 3 (STAT3) were examined by H&E staining and immunohistochemistry. RESULTS: Laboratory indexes in the four model groups were significantly different from those in the Control group (p < 0.01); indicators of the IMQ + STZ, IMQ + BSS, and IMQ + STZ + BSS groups showed varying degrees of difference from those of the IMQ group. CONCLUSIONS: The established mouse models of psoriasis blood stasis syndrome complicated with glucose and lipid metabolism disorders met the clinical and Chinese Medicine characteristics, and thus they could be used as animal models in future studies of psoriasis complicated with glucose and lipid metabolism disorders.

Cathode Material Determines Product Selectivity for Electrochemical C-H Functionalization of Biaryl Ketoximes.

The synthesis of polycyclic N-heteroaromatic compounds and their corresponding N-oxides has been developed through electrochemical C-H functionalization of biaryl ketoximes. The oxime substrates undergo dehydrogenative cyclization when a Pt cathode is used, resulting in unprecedented access to a wide range of N-heteroaromatic N-oxides. The products of the electrosynthesis are switched to the deoxygenated N-heteroaromatics by employing a Pb cathode through sequential anode-promoted dehydrogenative cyclization and cathodic cleavage of the N-O bond in the initially formed N-oxide.

Efficacy and safety of Tripterygium wilfordii hook F for chronic urticaria: a systematic review and meta-analysis.

BACKGROUND: The first-line agents comprising antihistamines for chronic urticaria, are not completely satisfactory. Tripterygium wilfordii Hook F (TwHF), a Chinese herb, has been developed into several Tripterygium agents and have definite effects on autoimmune and inflammatory diseases. In chronic urticaria, however, their values of practical application remain unclear. The aim of this study was to investigate the efficacy and safety of TwHF in patients with chronic urticaria. METHODS: Several databases were systematically searched including PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, Chinese Scientific Journals Database, Wan Fang Database, and Chinese Biomedicine. Randomized controlled trials comparing antihistamines with TwHF or Tripterygium agents in combination with antihistamines were included. Revman5.3 was utilized to calculate risk ratios (RR) with 95% confidence intervals (CI). This study was registered with PROSPERO, number CRD42018091595. RESULTS: Twenty-one trials with 2565 participants were included in this analysis. Meta-analysis showed that, when antihistamines were combined with TwHF and Tripterygium agents, the curative effect in cases of chronic urticaria was superior to that of antihistamines alone (RR: 1.40; 95% CI: 1.33-1.46). The incidence rates of gastrointestinal disorder (RR: 2.91; 95% CI: 1.70-4.99) and menstrual disorder (RR: 6.00; 95% CI: 1.79-20.13) in drug combination groups were higher than those in controls, while other adverse events were similar between the two groups. After treatment, Dermatology Life Quality Index (RR: 1.23; 95% CI: 1.09-1.40), quality of sleep (RR: 1.50; 95% CI: 1.07-2.12), and daily activity (RR: 1.49; 95% CI: 1.25-1.78) were all improved. Furthermore, drug combination groups demonstrated less relapse (RR: 0.34; 95% CI: 0.25-0.45). CONCLUSIONS: TwHF and Tripterygium agents, in combination with antihistamines, appear to be more effective than antihistamines alone. Nevertheless, adverse events cannot be ignored. Large sample, multi-center, high-quality clinical studies are needed to verify the exact effects and safety of TwHF and Tripterygium agents in treatment of chronic urticaria.

Reagent-Free C-H/N-H Cross-Coupling: Regioselective Synthesis of N-Heteroaromatics from Biaryl Aldehydes and NH3.

An unprecedented synthesis of N-heteroaromatics from biaryl aldehydes and NH3 through reagent-free C-H/N-H cross-coupling has been developed. The electrosynthesis uses NH3 as an inexpensive and atom-economic nitrogen donor, requires no oxidizing agents, and allows efficient and regioselective access to a wide range of phenanthridines and structurally related polycyclic N-heteroaromatic products.

Amidinyl Radical Formation through Anodic N-H Bond Cleavage and Its Application in Aromatic C-H Bond Functionalization.

We report herein an atom-economical and sustainable approach to access amidinyl radical intermediates through the anodic cleavage of N-H bonds. The resulting nitrogen-centered radicals undergo cyclizations with (hetero)arenes, followed by rearomatization, to afford functionalized tetracyclic benzimidazoles in a highly straightforward and efficient manner. This metal- and reagent-free C-H/N-H cross-coupling reaction exhibits a broad substrate scope and proceeds with high chemoselectivity.

Electrochemical C-H/N-H Functionalization for the Synthesis of Highly Functionalized (Aza)indoles.

Indoles and azaindoles are among the most important heterocycles because of their prevalence in nature and their broad utility in pharmaceutical industry. Reported herein is an unprecedented noble-metal- and oxidant-free electrochemical method for the coupling of (hetero)arylamines with tethered alkynes to synthesize highly functionalized indoles, as well as the more challenging azaindoles.

The cyano group as a traceless activation group for the intermolecular [3+2] cycloaddition of azomethine ylides: a five-step synthesis of (±)-isoretronecanol.

The cyano group was used as a traceless activation group for the [3+2] cycloaddition of azomethine ylides in a two-step process, thereby providing a highly effective approach to 5-unsubstituted pyrrolidines. The transformation includes the silver acetate catalyzed intermolecular 1,3-dipolar cycloaddition of α-iminonitriles and an unprecedented sodium borohydride induced reductive decyanation reaction. A diverse array of substrates is amenable to this transformation. The methodology was further extended to a five-step total synthesis of the pyrrolizidine natural product isoretronecanol.