Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

Clinical sequencing defines the somatic and germline mutation landscapes of Chinese HER2-Low Breast Cancer.

More than half of the breast cancer initially labeled as human epidermal growth factor receptor 2 (HER2)-negative actually exhibited low HER2 levels (IHC 1+ or IHC 2+/FISH-) and were classified as HER2-low breast cancer. Previous research emphasized the significant biological heterogeneity in HER2-low breast cancer, highlighting the importance of accurately characterizing HER2-low tumors to promote the precise management of antibody‒drug conjugates. In this study, we established a large-scale targeted sequencing cohort (N = 1907) representing Chinese HER2-low breast cancer patients with detailed clinical annotation. Our research findings revealed that HER2-low breast cancer demonstrated distinct clinical pathological characteristics and mutation landscapes compared to HER2-zero group. When compared to HER2-zero tumors, HER2-low tumors exhibited a higher proportion of Luminal B subtypes and better disease-free survival. In hormone receptor (HR)-positive breast cancer, HER2-low group showed a higher frequency of GATA3 somatic mutations, BRCA2 germline mutations, and mutations in the DNA damage repair pathway. In contrast, in HR-negative breast cancer, the HER2-low group displayed a higher frequency of PIK3CA mutations and PI3K pathway alterations. These findings offered valuable insights for the precise targeted treatment of HER2-low breast cancer in different HR statuses.

Intestinal lysozyme1 deficiency alters microbiota composition and impacts host metabolism through the emergence of NAD+-secreting ASTB Qing110 bacteria.

The intestine plays a pivotal role in nutrient absorption and host defense against pathogens, orchestrated in part by antimicrobial peptides secreted by Paneth cells. Among these peptides, lysozyme has multifaceted functions beyond its bactericidal activity. Here, we uncover the intricate relationship between intestinal lysozyme, the gut microbiota, and host metabolism. Lysozyme deficiency in mice led to altered body weight, energy expenditure, and substrate utilization, particularly on a high-fat diet. Interestingly, these metabolic benefits were linked to changes in the gut microbiota composition. Cohousing experiments revealed that the metabolic effects of lysozyme deficiency were microbiota-dependent. 16S rDNA sequencing highlighted differences in microbial communities, with ASTB_g (OTU60) highly enriched in lysozyme knockout mice. Subsequently, a novel bacterium, ASTB Qing110, corresponding to ASTB_g (OTU60), was isolated. Metabolomic analysis revealed that ASTB Qing110 secreted high levels of NAD+, potentially influencing host metabolism. This study sheds light on the complex interplay between intestinal lysozyme, the gut microbiota, and host metabolism, uncovering the potential role of ASTB Qing110 as a key player in modulating metabolic outcomes. IMPORTANCE: The impact of intestinal lumen lysozyme on intestinal health is complex, arising from its multifaceted interactions with the gut microbiota. Lysozyme can both mitigate and worsen certain health conditions, varying with different scenarios. This underscores the necessity of identifying the specific bacterial responses elicited by lysozyme and understanding their molecular foundations. Our research reveals that a deficiency in intestinal lysozyme1 may offer protection against diet-induced obesity by altering bacterial populations. We discovered a strain of bacterium, ASTB Qing110, which secretes NAD+ and is predominantly found in lyz1-deficient mice. Qing110 demonstrates positive effects in both C. elegans and mouse models of ataxia telangiectasia. This study sheds light on the intricate role of lysozyme in influencing intestinal health.

Potential antimicrobial activity of camel milk as a traditional functional food against foodborne pathogens in vivo and in vitro.

Foodborne pathogens are a leading cause of mortality worldwide. Therefore, strategies focused on functional foods are urgently required to tackle this issue. As a result, camel milk is one of the most important traditional functional foods since it contains a variety of bioactive components, which all have antimicrobial activity against foodborne pathogens. The study aims to investigate the potential antimicrobial activity of raw camel milk against foodborne pathogens in both in vitro agar well diffusion and infected mice, especially Listeria monocytogenes, Staphylococcus aureus, Salmonella Typhimurium and Escherichia coli, particularly in societies that rely on consuming camel milk in its raw form. A total of eighty C57BL/6 mice were divided into ten groups and gavaged with or without camel milk for two consecutive weeks. A blood plasma analysis and serum insulin levels were measured. Histological investigations of the liver, pancreas, kidney, spleen, lung and testicles were also performed. In both in vivo and in vitro studies when compared to other pathogenic bacteria, E. coli was the most affected by raw camel milk, with a significant clear zone of 2.9 ± 0.13 cm in vitro and in all measured parameters in vivo (p < 0.05). As a result, we advocated for further research to improve camel breeding, raise milk yield and extend its reproductive capability as one of the most important farm animals.

Clinical application status of multiple localization methods in the treatment of pulmonary nodules by sub-lobectomy / 中国胸心血管外科临床杂志

@#The precise localization of pulmonary nodules has become an important technical key point in the treatment of pulmonary nodules by thoracoscopic surgery, which is a guarantee for safe margin and avoiding removal of too much normal lung parenchyma. With the development of medical technology and equipment, the methods of locating pulmonary nodules are also becoming less trauma and convenience. There are currently a number of methods applied to the preoperative or intraoperative localization of pulmonary nodules, including preoperative percutaneous puncture localization, preoperative transbronchial localization, intraoperative palpation localization, intraoperative ultrasound localization, and localization according to anatomy. The most appropriate localization method should be selected according to the location of the nodule, available equipment, and surgeon鈥檚 experience. According to the published literatures, we have sorted out a variety of different theories and methods of localization of pulmonary nodules in this article, summarizing their advantages and disadvantages for references.

Posture planning method for complex feature measurement using a single-line laser scanner.

A single-line laser scanner is commonly utilized for measuring complex surfaces and contours. However, achieving automatic implementation of this scanner poses challenges in terms of designing a measurement posture that considers measurement accuracy, path planning, and the positioning of auxiliary equipment. This ensures non-interference during the measurement process. In this study, we focus on the application of T-SCAN. First, we construct a measurement posture parameter model for T-SCAN and analyze the viewpoint position's coverage of the measurement area. Second, we propose a measurement path planning method based on scanning posture to minimize overlapping areas. Lastly, we present a measurement station planning method based on scanning postures and analyze the transfer error of the measurement targets to establish a unified measurement field. Experimental results demonstrate that, after the posture adjustment process, the average distance deviation between the measurement data and the theoretical model is significantly reduced.

Structural Characterization and Immunomodulatory Activity of a Mannose-Rich Polysaccharide Isolated from Bifidobacterium breve H4-2.

In this study, a novel homogeneous mannose-rich polysaccharide named EPS-1 from the fermentation broth of Bifidobacterium breve H4-2 was isolated and purified by anion exchange column chromatography and gel column chromatography. The primary structure of EPS-1 was analyzed by high-performance liquid chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance. The results indicated that EPS-1 had typical functional groups of polysaccharides. EPS-1 with an average molecular weight of 3.99 × 104 Da was mainly composed of mannose (89.65%) and glucose (5.84%). The backbone of EPS-1 was →2,6)-α-d-Manp-(1→2)-α-d-Manp-(1→2,6)-α-d-Manp-(1→2)-α-d-Manp-(1→2,6)-α-d-Manp-(1→6)-α-d-Glcp-(1→ simultaneously containing two kinds of branched chains (α-d-Manp-(1→3)-α-d-Manp-(1→ and α-d-Manp-(1→). Besides, EPS-1 had a triple-helical conformation and exhibited excellent thermal stability. Moreover, the immunomodulatory activity of EPS-1 was evaluated by RAW 264.7 cells. Results indicated that EPS-1 significantly enhanced the viability of RAW 264.7 cells. EPS-1 could also be recognized by toll-like receptor 4, thereby activating the nuclear factors-κB (NF-κB) signaling pathway, promoting phosphorylation of related nuclear transcription factors, improving cell phagocytic activity, and promoting the secretion of NO, IL-6, IL-1ß, and TNF-α. Thus, EPS-1 could activate the TLR4-NF-κB signaling pathway to emerge immunomodulatory activity on macrophages. The above results indicate that EPS-1 can serve as a potential immune-stimulating polysaccharide.

Development of a tetra-primer ARMS-PCR for identification of sika and red deer and their hybrids.

Accurate identification of deer-derived components is significant in food and drug authenticity. Over the years, several methods have been developed to authenticate these products; however, identifying whether female deer products are hybrids is challenging. In this study, the zinc finger protein X-linked (ZFX) gene sequences of sika deer (Cervus nippon), red deer (Cervus elaphus) and their hybrid offspring were amplified and sequenced, the X221 and X428 species-specific single nucleotide polymorphisms (SNP) loci were verified, and a tetra-primer amplification refractory mutation system (T-ARMS-PCR) assay was developed to identify the parent-of-origin of female sika deer, red deer, and their hybrid deer. The T-ARMS-PCR developed based on the X221 locus could identify sika deer, red deer, and their hybrid offspring according to the presence or absence of PCR product sizes of 486 bp, 352 bp, and 179 bp, respectively, just as X428 locus could identify sika deer, red deer, and their hybrid offspring according to the presence or absence of PCR product sizes of 549 bp, 213 bp, and 383 bp, respectively. Forty products labeled deer-derived ingredients randomly purchased were tested using this assay, and the results showed that the identification results based on the two SNP loci were utterly consistent with the actual sources. In addition, this method was found to be accurate, simple, convenient, and with high specificity, thus providing an essential technical reference for deer product species identification. It is also an important supplement to the identification methods of the original ingredients of existing deer products.

Trichomonas gallinae Kills Host Cells Using Trogocytosis.

Trichomonas gallinae (T. gallinae) is an infectious parasite that is prevalent worldwide in poultry and can cause death in both poultry and wild birds. Although studies have shown that T. gallinae damages host cells through direct contact, the mechanism is still unclear. In this study, we found that T. gallinae can kill host cells by ingesting fragments of the host cells, that is, by trogocytosis. Moreover, we found that the PI3K inhibitor wortmannin and the cysteine protease inhibitor E-64D prevented T. gallinae from destroying host cells. To the best of our knowledge, our study has demonstrated for the first time that T. gallinae uses trogocytosis to kill host cells. Understanding this mechanism is crucial for the prevention and control of avian trichomoniasis and will contribute to the development of vaccines and drugs for the prevention and control of avian trichomoniasis.

Glucose metabolism profile recorded by flash glucose monitoring system in patients with hypopituitarism during prednisone replacement.

BACKGROUND: Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications. AIM: To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes. METHODS: Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet ß-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs. RESULTS: Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet ß-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-ß compared with that of NCs; a notable difference in HOMA-ß was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-ß, and fasting glucose/insulin ratio when compared with NCs. CONCLUSION: Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.

Identification of new drug candidates against Trichomonas gallinae using high-throughput screening.

Trichomonas gallinae is a protozoan parasite that is the causative agent of trichomoniasis, and infects captive and wild bird species throughout the world. Although metronidazole has been the drug of choice against trichomoniasis for decades, most Trichomonas gallinae strains have developed resistance. Therefore, drugs with new modes of action or targets are urgently needed. Here, we report the development and application of a cell-based CCK-8 method for the high-throughput screening and identification of new inhibitors of Trichomonas gallinae as a beginning point for the development of new treatments for trichomoniasis. We performed the high-throughput screening of 173 anti-parasitic compounds, and found 16 compounds that were potentially effective against Trichomonas gallinae. By measuring the median inhibitory concentration (IC50) and median cytotoxic concentration (CC50), we identified 3 potentially safe and effective compounds against Trichomonas gallinae: anisomycin, fumagillin, and MG132. In conclusion, this research successfully established a high-throughput screening method for compounds and identified 3 new safe and effective compounds against Trichomonas gallinae, providing a new treatment scheme for trichomoniasis.

Activation of CREB-binding protein ameliorates spinal cord injury in tabersonine treatment by suppressing NLRP3/Notch signaling.

Introduction: Spinal cord injury (SCI) alters the integrity of the spinal cord, which leads to loss of multiple organs' function including locomotor function. The present study evaluates the protective effect of tabersonine against SCI. Material and methods: SCI was induced by traumatic injury and animals were treated with tabersonine 20 and 40 mg/kg, intraperitoneally for the period of 10 days. Tabersonine's effect was determined by estimating locomotor and neurological function in spinal cord injured rats. Moreover, mediators of inflammation were estimated using enzyme-linked immunosorbent assay (ELISA) and the effect of tabersonine on Notch/inflammasome signaling was estimated by reverse transcription polymerase chain reaction (RT-PCR), western blot assay and immunohistochemistry. Apoptosis of neuronal cells was estimated by staining with Nissl stain on spinal cord tissue in SCI rats. Results: Data of the study suggest that neurological and motor functions were improved in the tabersonine treated group compared to the spinal cord injured (SI) group. There was a decrease in the mediators of inflammation in the spinal cord tissue of the tabersonine treated group compared to the SI group. Treatment with tabersonine ameliorates the altered expression of NICD, Nestin and Hes-1 protein and mRNA expression of Notch-1 and Hes-1 in the SCI rats. It was also observed that the tabersonine treated group showed activation of CREB and inhibition of the NLRP-3 pathway in SCI rats. Moreover, apoptosis of neuronal cells was reduced in the tabersonine treated group compared to the SI group. Conclusions: Data of the investigation suggest that tabersonine protects against spinal cord injury by activating CREB and reducing NLRP3/Notch signaling.

Male-Biased Parasitism of Brandt's Voles (Lasiopodomys brandtii) in Inner Mongolia, China.

The abundance and prevalence of parasitic infection often vary in different host sexes, and this phenomenon has been named sex-biased parasitism. Brandt's voles are the dominant rodent species in typical steppe habitat and are widely distributed in Inner Mongolia, China, but the prevalence of parasites in Brandt's voles are poorly reported. In this study, we investigated the prevalence of six intestinal parasites in Brandt's voles in May, June, July, and August 2022 around the Xilingol Grassland in Inner Mongolia, China. The results showed that Syphacia obvelata, Aspiculuris tetraptera, and Trichostrongylidae family were the dominant intestinal parasites in Brandt's voles that we captured in this study, and the infection rates of the three parasites were significantly higher in males than females, which showed obvious male-biased parasitism. Season and human activities such as grazing had no significant effect on the infection rates for different parasites, while the parasite reproduction level was higher when the ambient temperature was around 18 °C. Sexual size dimorphism was ubiquitous in Brandt's voles, and it was mainly manifested by the differences in body weight and length between males and females. Simple linear regression analysis showed a significant positive correlation between bodyweight and parasite infection rates, so the sex-biased parasitism in Brandt's voles could be explained by the body size hypothesis, as a larger body could provide more ecological niches for parasitic infection.

Optimization of underground open intermediary space comfort in TOD complexes: A case study of Chongqing, China.

Rapid urbanization drives social development, but at the same time brings sustainable development Rapid urbanization drives social development, but at the same time brings sustainable development advantages of expanding underground space and relieving urban traffic congestion. High quality TOD complexes with natural elements in the intermediary space have been considered as one of the important means to address sustainable urban development. Nevertheless, intermediary spaces in TOD complexes face various challenges, such as significant contradictory factors in their physical environment spaces. This study classifies the underground open intermediary space into four types according to the characteristics of TOD complexes. And for these four types'Cthe physical environment-generated by various influencing factors of planar geometric, three-dimensional geometric, and detailed construction elements-is simulated using a numerical simulation method based on a static Taguchi experiment. The results demonstrate that space shape is a primary influencing factor for luminous and thermal environments; the window-atrium ratio (W/A ratio) and hole-atrium ratio (H/A ratio) comprise contradictory factors between the luminous and thermal environments of these spaces; profile inclination angle and sunken plaza height are primary impact factors for the acoustic environment; and skylight type has minimal influence on the physical environment. On average, their luminous and acoustic environment comfort can be improved by 200%; whereas, their thermal environment comfort can be improved by 21% and the potential for optimizing it in their shallow space (underground space depth ≤ 10 m) is relatively low. Subsequently, the necessity of comfort optimization as the passive optimization design of underground open intermediary spaces' physical environment in TOD complexes in the future is discussed. Finally, the feasible path and prospect of how to improve the livability and comfort of the spatial physical environment of TOD complexes are discussed and prospected.

Infection of Trichinella spiralis Affects the Reproductive Capacity of ICR/CD-1 Male Mice by Reducing the Urine Pheromone Contents and Sperm Quality.

Female mice can discriminate the urinary odors of male mice due to their olfactory acuity. Parasitic infection or subclinical infection can decrease the odor attractiveness of male mice and finally lead to aversion or avoidance responses in odor selection for female mice. Trichinella spiralis is a kind of tissue-parasitizing nematode that causes trichinellosis, a zoonotic parasitic disease that spreads throughout the world. However, the reproductive injury caused by Trichinella spiralis infection was not fully revealed. In this study, we explored the effect of Trichinella spiralis infection on the reproductive capacity in ICR/CD-1 male mice. We identified eight volatile compounds in urine by GC-MS analysis, and the results indicated that the contents of dimethyl sulfone, Z-7-tetradecen-1-ol, 6-Hydroxy-6-methyl-3-heptanone and (S)-2-sec-butyl-4,5-dihydrothiazole were significantly downregulated after parasitic infection, which might lead to the reduction of attractiveness of male mice urine to females. On the other hand, parasitic infection decreased sperm quality and downregulated the expression levels of Herc4, Ipo11, and Mrto4, and these genes were strongly related to spermatogenesis. In summary, this study revealed that the reproductive injury caused by Trichinella spiralis infection in ICR/CD-1 male mice could be associated with a decrease in urine pheromone content and sperm quality.

Infection with Cryptosporidium parvum Affects Secondary Sexual Characteristics of Male Mice by Altering the Pheromone Content in Preputial Gland.

The olfactory acuity of female mice allows them to discriminate the urinary odors of males. Parasitic infection can reduce the odor attractiveness of male mice to females and result in female aversion or avoidance responses in odor selection. However, the chemical signaling changes in the pheromone contents produced by the foreskin gland were not fully revealed after parasitic infection. Cryptosporidium parvum (C. parvum) is a common zoonotic intestinal parasite and has a wide range of hosts, including human, domestic animals, and wild animals. In this study, we immunosuppressed ICR/CD-1 male mice by dexamethasone sodium phosphate treatment. After C. parvum infection, physiological indexes such as body weight and organ weight were significantly decreased. Furthermore, the gene expression level of MUP (major urinary protein) in liver and urine were significantly down-regulated, which could be the reason for the decrease in urine attractiveness to females. GC-MS was performed to analyze the changes in the pheromone produced by the preputial gland before and after parasitic infection, and the results indicated that the levels of different pheromones were significantly reduced after parasitic infection. In summary, this study reveals that C. parvum infection damages the secondary sexual characteristics of male ICR/CD-1 male mice and decreases the pheromone content produced by the foreskin gland.

WITHDRAWN: Hidrosmin Attenuates Inflammatory Response Induced by IL1ß by Suppressing the Activation of NF-κB Involving Nrf2/HO1 Pathway in Human Osteoarthritis Chondrocytes

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the journal "Current Cancer Drug Targets"Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Effects and mechanism of veratramine on the proliferation of human glioblastoma U251 cells / 中国药房

OBJECTIVE To explore the effects and potential mechanism of veratramine （VTM） on the proliferation of human glioblastoma U251 cells. METHODS The network pharmacology methods were adopted to screen the targets of ferroptosis related to the effects of VTM on glioblastoma， and to conduct gene ontology and Kyoto Encyclopedia of Genes and Genosomes enrichment analysis. Using U251 cells as the object， CCK-8 assay， the observation of cell morphological changes， DCFH-DA fluorescence probe method， FerroOrange fluorescence probe method and Western blot assay were used to validate the inhibitory effects of VTM on U251 cell proliferation and its possible mechanism. RESULTS Totally 462 targets of ferroptosis related to the effects of VTM on glioblastoma were screened out； they mainly enriched in biological processes such as oxidative stress and apoptosis， and cellular components such as cytoplasmic vesicles and mitochondrial membranes； they affected molecular functions such as iron ion （Fe2+） binding and DNA transcription processes， as well as iron death and phosphoinositide 3-kinase/protein kinase B signaling pathways. VTM with 40， 60， 80， 100， 120 and 140 μmol/L could significantly reduce the cell survival rate （P＜ 0.01）； VTM with 40， 80 and 120 μmol/L could cause cell atrophy and nuclear fragmentation， significantly inhibit the clone formation， increase the levels of intracellular reactive oxygen species （ROS） and Fe2+ levels， increase the expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） protein to different extents， while down-regulate the expression of glutathione peroxidase 4 （GPX4） protein （P＜0.05 or P＜0.01）. CONCLUSIONS VTM can inhibit the proliferation of U251 cells， and promote the accumulation of intracellular ROS and Fe2+， thus inducing ferroptosis； its mechanism might be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

Efficacy of omalizumab in the treatment of chronic urticaria patients with poor response to antihistamines: a single-center retrospective study / 中华皮肤科杂志

Objective:To investigate the efficacy and safety of omalizumab in the treatment of chronic urticaria (CU) patients with poor response to H1 antihistamines.Methods:CU patients, who showed poor response to H1 antihistamines and received omalizumab treatment, were collected from the Department of Dermatology, Xiangya Hospital, Central South University from June 2020 to June 2021. The efficacy of omalizumab was evaluated by using the 7-day urticaria activity score (UAS7) and urticaria control test (UCT) score at weeks 4, 12 and 24 after the start of treatment. The t-test, chi-square test, and Pearson correlation analysis were used to analyze the relationship between the clinical characteristics and efficacy. Results:A total of 121 CU patients who met the inclusion criteria and had relatively complete medical records were included in this study, including 54 males (44.63%) and 67 females (55.37%) , and their ages ranged from 13 to 70 years (39.88 ± 14.36 years) ; 88 patients were diagnosed with chronic spontaneous urticaria (72.73%) , 10 with chronic inducible urticaria (8.26%) , and 23 with chronic spontaneous urticaria accompanied by chronic inducible urticaria (19.01%) . At week 4 after the start of omalizumab treatment, the response rate was 50.86% (59/116) , and the complete response rate was 25.86% (30/116) ; at week 12, the response rate was 78.26% (54/69) , and the complete response rate was 34.78% (24/69) ; at week 24, the response rate was 64.71% (22/34) , and the complete response rate was 23.53% (8/34) . At week 4, CU patients with baseline serum total IgE levels of < 40 IU/ml had a lower response rate (26 cases, 30.77%) than those with baseline serum total IgE levels of ≥ 40 IU/ml (61 cases, 65.57%; χ2 = 8.93, P = 0.004) . Correlation analysis showed that the age at treatment, age at onset, allergic diseases, concomitant symptoms, baseline erythrocyte sedimentation rates, and baseline C-reactive protein levels were significantly correlated with the UCT scores (all P < 0.05) , while the course of disease, clinical types, serum total IgE levels, peripheral blood counts, dermatology life quality index scores, and UAS7 scores were not significantly correlated with the UCT scores. Among the 121 CU patients, 8 (6.61%) reported mild to moderate adverse reactions. Conclusion:Omalizumab could effectively improve clinical symptoms and signs of CU patients with poor response to H1 antihistamines, and was well tolerated;omalizumab treatment may be more beneficial to patients without allergic comorbidities such as allergic rhinitis, without concomitant symptoms such as angioedema, and with lower erythrocyte sedimentation rates and C-reactive protein levels.