Dupliumab therapy for alopecia areata: a case series and review of the literature.

BACKGROUND: A growing body of research supports the important role of the TH2 axis in alopecia areata (AA). Dupilumab is a humanized monoclonal antibody against IL-4Rα that downregulates TH2 response. Although efficacy has been shown in clinical trials, real-world data on the use of dupilumab in AA patients is limited. OBJECTIVES: To report on a case series of 10 patients with AA who were treated with dupilumab and provide real-world evidence regarding its efficacy in treating severe AA. METHODS: In this retrospective single-center study, all AA patients treated with dupilumab treatment were included between May 2022 and October 2023. Clinical outcome measures (Severity of Alopecia Tool, SALT) and adverse events (AEs) were analyzed. In addition, a literature review was conducted to summarize the efficacy of AA with dupilumab and the characteristics of patients previously reported in the literature. RESULTS: We identified 10 patients with AA who were or are being treated with dupilumab, with a median (range) treatment duration of 8 (3-15) months. Of these, four patients have high serum immunoglobulin E (IgE) levels (≥200IU/ml). The mean (IQR) pretreatment SALT score was 79% (52-100). Seven of 10 patients achieved at least 50% re-growth. Of those who improved, the mean (IQR) percentage change in SALT score at 3 months and the end of follow-up was 57% (29%-89%) and 95% (68-100), respectively. Notably, seven patients (70%) had white hair regrowth, with the white hair slowly decreasing over time and the proportion of pigmented black hair increasing. Dupilumab was well tolerated by all patients. No adverse events were reported. CONCLUSIONS: Overall, our research supports dupilumab as another candidate that possesses potential benefits for AA. High levels of IgE may be not prerequisites for dupilumab's successful treatment response.

Drug Survival and Long-term Outcome of Tofacitinib in Patients with Alopecia Areata: A Retrospective Study.

Several non-randomized clinical trials and retrospective studies have demonstrated encouraging efficacy and well-tolerated safety of tofacitinib in the treatment of alopecia areata. However, there are scarce data on a large cohort of patients with alopecia areata in long-term real-world practice. This single-centre, retrospective, observational cohort study included 126 patients with alopecia areata treated with tofacitinib between February 2021 and December 2022. The aims of this study are to evaluate drug survival, effectiveness and safety of tofacitinib for treatment of alopecia areata, and to identify potential factors influencing long-term outcomes. Median duration of treatment was 23.00 (interquartile range (IQR) 15.00, 47.25) weeks. Median all-cause survival time of 126 patients treated with tofacitinib was 44 weeks (95% confidence interval (95% CI) 36.3, 51.7), and the all-cause drug retention rate at 12 weeks, 24 weeks and 48 weeks were 90.0%, 66.4% and 42.3%, respectively. The most common reason for discontinuation was complete remission/satisfaction. A total of 80 patients treated with tofacitinib for over 6 months were included in the efficacy analysis, the overall complete response rate at 24 weeks was 33.8% (27/80). No life-threatening serious adverse events occurred. Sex is an independent risk factor in predicting patient outcomes. This real-world study confirmed the high effectiveness and acceptable safety profile of tofacitinib in alopecia areata, with a satisfactory drug survival rate, and provides supporting data for the clinical application of tofacitinib in Chinese patients with alopecia areata.

Effects of natural spring water on the sensory attributes and physicochemical properties of tea infusions.

The sensory quality of tea is influenced by water quality, with natural spring water (NSW) gaining much attention for its natural and healthy qualities. The effects of NSW on the sensory attributes, physicochemical composition, and antioxidant capacity of Chinese tea were investigated. Tea brewed with pure water was the most resistant to oxidation and darkening. NSW with low total dissolved solids (TDS) was most suitable for brewing unfermented or mildly fermented teas, improving their sensory quality. The simulated green tea infusion system was used to investigate further the dramatic darkening of tea infusions in NSW. Exposure of infusions to air promoted the degradation, epimerization, and oxidative polymerization of catechins, and further formed theabrownins which darkened the tea infusions. These findings enabled tea consumers to choose the most suitable NSW for brewing Chinese teas and illustrated the darkening mechanism of tea infusion in high pH/TDS water.

Case report: Rubella virus-induced cutaneous granulomas in a girl with atypical SCID caused by DCLRE1C gene mutations.

Here, we report a case of rubella virus-induced granulomatous dermatitis in a young girl with immunodeficiency caused by DCLRE1C gene mutations. The patient was a 6-year-old girl who presented with multiple erythematous plaques on the face and limbs. Biopsies of the lesions revealed tuberculoid necrotizing granulomas. No pathogens could be identified on extensive special stains, tissue cultures, or PCR-based microbiology assays. Metagenomic next-generation sequencing analysis revealed the rubella virus. Underlying atypical severe combined immunodeficiency was recognized based on the patient's history of repetitive infections since birth, low T-cell, B-cell, and NK cell counts, and abnormal immunoglobulins and complements. Whole-exome sequencing revealed the genetic abnormality of the atypical severe combined immunodeficiency (SCID), and compound heterozygous mutations of the DCLRE1C gene were detected. This report highlights the diagnostic values of metagenomic next-generation sequencing in identifying rare pathogens causing cutaneous granulomas in patients with atypical SCID.

Tuberous sclerosis complex with skin lesions as the initial presentation: A case report and multidisciplinary discussion. / 1例以皮肤损害为首发症状的结节性硬化症并多学科讨论.

We reported a case of tuberous sclerosis complex with facial angiofibroma as the initial presentation and conducted a multidisciplinary discussion. The patient, a young female, was admitted to the Department of Dermatology for cosmetic purpose. After the examination, she was found to have multiple system involvement, including a large renal angiomyolipoma pressing on the liver. She never had any subjective symptom. After consultation by the multidisciplinary team of tuberous sclerosis complex, the patient was treated with everolimus orally and followed up regularly. It is suggested that dermatologists should pay attention to the systemic involvement of patients with tuberous sclerosis complex. Early intervention can prolong the life of patients and improve their life quality. Multidisciplinary collaboration for lifelong disease management is the key to enhance the diagnosis and treatment for tuberous sclerosis complex and enhance the prognosis of patients.

Mellow and Thick Taste of Pu-Erh Ripe Tea Based on Chemical Properties by Sensory-Directed Flavor Analysis.

The mellow and thick taste is a unique characteristic of pu-erh ripe tea infusion, and it is closely related to the chemical composition of pu-erh ripe tea, which is less studied. This paper clarifies and compares the chemical composition of pu-erh ripe tea to that of the raw materials of sun-dried green tea, and uses membrane separation technology to separate pu-erh ripe tea into the rejection liquid and the filtration liquid. The results show that microorganisms transformed most physicochemical components, except caffeine, during the pile fermentation. It was found that total tea polyphenols, soluble proteins, total soluble sugars, theabrownin, and galloylated catechins became enriched in the rejection liquid, and the rejection liquid showed a more obvious mellow and thick characteristic. Taste interactions between crude protein, crude polysaccharide, and theabrownin were determined. They illustrated that the mellow and thick taste of pu-erh ripe tea with the addition of theabrownin increased from 4.45 to 5.13. It is of great significance to explore the chemical basis of the mellow and thick taste in pu-erh tea for guiding the pu-erh tea production process and for improving the quality of pu-erh tea.

A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis.

Circular RNAs (circRNAs) are a novel class of widespread noncoding RNAs that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open reading frames in noncoding RNAs, including circRNAs. However, the role of circRNAs in various physiological and pathological states, such as cancer, is not well understood. In this study, through deep RNA sequencing on human endometrial cancer (EC) samples and their paired adjacent normal tissues, we uncovered that the circRNA hsa-circ-0000437 is significantly reduced in EC compared with matched paracancerous tissue. The hsa-circ-0000437 contains a short open reading frame encoding a functional peptide termed CORO1C-47aa. Overexpression of CORO1C-47aa is capable of inhibiting angiogenesis at the initiation stage by suppressing endothelial cell proliferation, migration, and differentiation through competition with transcription factor TACC3 to bind to ARNT and suppress VEGF. CORO1C-47aa directly bound to ARNT through the PAS-B domain, and blocking the association between ARNT and TACC3, which led to reduced expression of VEGF, ultimately lead to reduced angiogenesis. The antitumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has potential value in anticarcinoma therapies and warrants further investigation.

Application of different foliar iron fertilizers for enhancing the growth and antioxidant capacity of rice and minimizing cadmium accumulation.

Iron (Fe) fertilizer can reduce cadmium (Cd) uptake and toxicity in rice, but the underlying mechanisms of Cd mitigation by different fertilizers are poorly understood. Here, pot experiments in rice were conducted to characterize the effects of four types of foliar-applied Fe fertilizer (chelated ferrous Fe, ferric Fe, ionic ferrous Fe, and ferric Fe) at three doses (20, 50, and 100 mg L-1) on photosynthetic capacity, antioxidant ability, yield, and Cd accumulation in Cd-contaminated soil. The results showed that foliar Fe application increased the net photosynthesis rate by 19.3%, peroxidase (POD) by 18.2%, superoxide dismutase (SOD) by 26.9%, and catalase (CAT) by 19.6%, and led to a 7.2% increase in grain yield compared with the control. Moreover, foliar Fe application significantly reduced Cd accumulation by 15.9% in brown rice and decreased the translocation of Cd from roots to other plant tissues. Overall, application of moderate doses (50 mg L-1) of chelated ferrous Fe was the most effective method for reducing Cd uptake (decreasing the Cd concentration in brown rice by 29.0%) and toxicity in rice (decreasing malondialdehyde by 23.2% and increasing POD, SOD, and CAT by 54.4%, 51.6%, and 45.7%, respectively), which may stem from the fact that chelated ferrous Fe was a more stable and bioavailable source of Fe for rice. The Cd concentration in rice had negative relationship with Fe concentration, and the translocation of Cd from root to the other tissues was reduced by the higher Fe nutrition status in leaf, suggesting that a high Fe supply may decrease Cd content by inhibiting the expression of the Fe transport system. These results indicate that foliar application of chelated ferrous Fe provides a promising alternative approach for enhancing growth and controlling Cd accumulation in rice plants. Furthermore, these results advance our understanding of the associations between plant Fe nutrition status and Cd accumulation.

Heavy metal distribution, translocation, and human health risk assessment in the soil-rice system around Dongting Lake area, China.

Heavy metals including copper (Cu), zinc (Zn), cadmium (Cd), chromium (Cr), lead (Pb), and arsenic (As) were investigated in 89 pairs of rice plant and paddy soils around Dongting Lake area, China. Rice plants and soils were collected with GPS device, and heavy metal contents in different rice plant tissues and soils were measured. The aim of the present study was to assess the heavy metal pollution and translocation in the whole soil-rice system, including the consequent human health risk for residents. According to the indices of average geoaccumulation (Igeo) of the studied elements, paddy soils in study area were moderately polluted by Cd, lowly polluted by Pb, and not polluted by Cu, Zn, Cr, and As. Considering the much higher concentrations of studied elements in roots than in other tissues of rice plants, a great mass of these elements was assumed to be confined in the roots. The low translocation factors from root to shoot (Tfroot-shoot) of all the studied heavy metals (0.04-0.74) underpinned this. The high translocation factors from soil to root (Tfsoil-root) of Cd (9.12), As (4.38), and Zn (2.05) indicated the high bioavailability of these heavy metals for rice plant. The health risk assessment using target hazard quotients (THQs) model indicated that Cd (5.17 for adults and 4.49 for children respectively) and As (3.61 for adults and 3.14 for children respectively) could cause human health risk both for adults and children. Further, given the rate of individual THQ values exceeding one, Cu might also be considered as a potential human health dangerous element in the study area. It was worth noting that as one of the main pollutants, Pb did not show human health risk through rice grain consumption due to its low Tf values in soil-rice system. However, the risk identification of As using comparisons of measured concentrations with risk screening value in Chinese paddy soil standard (GB15618-2018) was not consistent with the human health risk assessment result. This might indicate that site-specific risk screening values of As in China is in demand.

Antimony accumulation and iron plaque formation at different growth stages of rice (Oryza sativa L.).

To better understand the Sb phytoavailability in rice, we studied Sb accumulation in rice (Zhongjiazao-17, widely cultivated in Hunan province) at different growth stages based on adding SbIII and SbV to waterlogged soils in 10, 50 and 100 mg kg-1 treatment levels. Proportional exogenous SbIII and SbV remained in the soil solution after equilibration. In SbIII treatments, the iron plaque (IP) amounts and Sb in rice roots sharply increased from tillering to jointing stages and then reduced at the following stages. However, in SbV treatments, they increased continuously from tillering to maturing stages. The accumulation trends of Sb in straws, ears and grains were consistent in SbIII and SbV treatments, rising from tillering to jointing stages followed with reducing from jointing to flowering stages slightly, and rising again significantly from flowering to maturing stages. The Tfsoil-grain values in all the Sb treatments were low (0.77 × 10-3-5.1 × 10-3), However, when Sb in waterlogged soils were higher than 50 mg kg-1, it could pose human health risk for residents.

Uptake and accumulation of potentially toxic elements in colonized plant species around the world's largest antimony mine area, China.

To provide information on reclamation of multi-heavy metal polluted soils with conception of phytostabilization, a field survey on the uptake and accumulation of potentially toxic elements such as antimony (Sb), arsenic (As), lead (Pb), cadmium (Cd), copper (Cu), and zinc (Zn) in colonized plant species around the world's largest antimony mine area, China, was conducted. Samples including leaves and shoots (including roots and stems) of colonized plants as well as rhizospheric soils were collected from eight sampling zones in the studied area. The results showed that the contents of Cu, Zn, and Pb in rhizospheric soils below plants were comparable to the corresponding background values of Hunan province, otherwise Sb, Cd, and As contents were extremely high (17-106, 17-87, and 3-7 times of the corresponding background values). The highest concentration of Sb was found in Aster subulatus (410 mg kg-1); Cd, As, and Zn were in Herba bidentis bipinnatae (10.9, 264, and 265 mg kg-1, respectively); and Cu was in Artemisia lavandulaefolia (27.1 mg kg-1). It also exhibited that all the contents of As in leaves were several times of those in shoots of plants, Cd and other heavy metals showed in a similar pattern in several studied species, implying that the uptake route of these heavy metals via foliar might contribute to the accumulation. With high bioconcentration factors of heavy metals (more than 1, except for Zn), together with the growth abundance, Herba bidentis bipinnatae was considered as the most suitable colonized species for phytostabilization of the multi-heavy metal pollution in soils on this antimony mine area.

[Laparoscopic transhiatal proximal gastrectomy for adenocarcinoma of the esophagogastric junction: report of 98 cases].

OBJECTIVE: To explore the safety and short-term efficacy of laparoscopic transhiatal proximal gastrectomy in patients with adenocarcinoma of the esophagogastric junction. METHODS: From Aug 2008 to May 2011, 98 patients with adenocarcinoma of the esophagogastric junction underwent laparoscopic transhiatal proximal gastrectomy. Clinical data were analyzed retrospectively including operative time, estimated bleeding, length of resection, lymph node dissection, and short-term postoperative complications. RESULTS: Ninety-six patients underwent laparoscopic transhiatal proximal gastrectomy successfully and 2 were converted to open operation (one for combined splenectomy and the other combined splenectomy and resection of the tail of the pancreas). The mean operative time was (224.1±33.7) min and the mean blood loss was (69.4±26.1) ml. The mean length of esophageal resection was (4.0±0.6) cm and the resection margin was negative. The number of lymph node removed was 16.4±5.7. Pleural laceration occurred in 14 cases and spleen injury occurred in 3 case during operation. There was one anastomotic leakage. There were no postoperative mortalities, bleeding, anastomotic stenosis and wound infection. After follow-up ranging from 3 to 30 months, the value of reflux diagnostic questionnaire (RDQ) was 9.9±4.4 at 1 month and 9.3±4.3 at 3 months postoperatively. No incision metastasis was found and 5 patients died. CONCLUSION: Laparoscopic transhiatal proximal gastrectomy is safe for patients with adenocarcinoma of the esophagogastric junction and the short-term clinical outcomes are favorable.