BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Objective:To further explore the role and mechanism of hsa_circ_0001776 and mir-1265 in lung squamous carcinoma by verifying the expression level of hsa_circ_0001776 in plasma, tissues, and cells of lung squamous carcinoma.Methods:Plasma was collected from patients with lung squamous carcinoma treated at Tangshan People's Hospital and healthy individuals from 2020 to 2022. Lung squamous carcinoma tissue microarrays purchased from Shanghai Xinchao Biotechnology Company in 2022. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of hsa_circ_0001776 in lung squamous carcinoma plasma, tissues, and cells, and fluorescence in situ hybridization was used to verify the expression of hsa_circ_0001776 in lung squamous carcinoma. The localization of hsa_circ_0001776 in NCI-H1703 was verified by fluorescence in situ hybridization. The lung squamous carcinoma cells NCI-H1703 and NCI-H226 were cultured in vitro and divided into the circ-negative control (NC) group, hsa_circ_0001776 overexpression group, miR-NC group, miR-1265 mimic group, hsa_circ_0001776+miR-NC group, and hsa_circ_0001776+miR-1265 mimic group.The cell proliferation, motility and apoptosis were detected by the cell counting kit-8 (CCK-8) method, clone formation, Transwell invasion and migration, and scratch assay, and flow cytometry, respectively. The downstream of hsa_circ_0001776 was predicted by circular RNA interactome website, and the interaction between hsa_circ_0001776, miR-1265 was further determined by dual luciferase reporter gene assay, and nude mice subcutaneous tumorigenesis assay detected the growth of transplanted tumors. Results:Fluorescence in situ hybridization results showed that the fluorescence intensity of hsa_circ_0001776 in lung squamous carcinoma tissues was lower than that in paracancerous tissues, and the fluorescence intensity of miR-1265 in lung squamous carcinoma tissues was higher than that in paracancerous tissues (both P＜0.05). The expression level of hsa_circ_0001776 in the plasma of lung squamous carcinoma patients was lower than that in the plasma of healthy people, and the expression level of miR-1265 was higher than that in the plasma of healthy people (both P＜0.05). The expression levels of hsa_circ_0001776 in lung squamous carcinoma cells NCI-H1703, NCI-H226 and SK-MES-1 were lower than that in bronchial epithelial cells BEAS-2B (all P＜0.05), and the relative expression levels of miR-1265 in NCI-H1703 and NCI-H226 were higher than that in human bronchial epithelial cells BEAS -2B (all P＜0.05). The expression of hsa_circ_0001776 was correlated with age, lymph node metastasis, clinical stage, and tumor stage in patients with lung squamous carcinoma (all P＜0.05). Fluorescence in situ hybridization results showed that hsa_circ_0001776 was mainly expressed in the cytoplasm. The results of dual-luciferase reporter assay showed complementary binding of miR-1265 to hsa_circ_0001776. The absorbance values of the hsa_circ_0001776 overexpression group in NCI-H1703 and NCI-H226 cells were lower than that of the circ-NC group ( P＜0.05). The number of cell clones in the hsa_circ_0001776 overexpressed group was (52±3) and (53±4), the number of migrating cells was (476±17) and (113±7), the number of invading cells was (100±2) and (184±2), and the cell migration rate was (25.00±4.36)% and (36.02±5.55)%, which were lower than those of the circ-NC group [(104±4) and (106±2), (783±29) and (517±16), (657±45) and (473±9), (48.95±8.69)% and (48.70±1.57)%, all P＜0.05]. The apoptosis rates in the overexpression hsa_circ_0001776 group were (24.77±2.303)% and (19.67±1.16)%, respectively, both higher than those in the circ-NC group [(11.83±1.15)% and (9.50±0.66)%, respectively, both P＜0.05]. MiR-1265 mimic group had a higher apoptotic rate in the NCI-H1703 and NCI-H226 than those of the miR-NC groups ( P＜0.05). miR-1265 mimic group had (56±13) and (51±8) cell clones, (556±13) and (405±6) migrating cells, (486±6) and (359±7) invading cells, cell migration rates of (68.56±5.51)%, (81.74±8.04)%, were higher than those of miR-NC group [(31±4) and (21±8), (154±19) and (186±5), (227±6) and (176±7), (25.83±4.26)% and (53.12±4.14) %, all P＜0.05]. The apoptotic rates in the miR-1265 mimic group were (11.83±2.55)% and (17.50±1.05)%, respectively, which were lower than those in the miR-NC group [(32.67±4.44)% and (39.90±2.88)%, respectively, both P<0.05]. The absorbance values of NCI-H1703 and NCI-H226 in the overexpression of hsa_circ_0001776+miR-1265 mimic group were higher than those of the overexpression of hsa_circ_0001776+miR-NC group ( P<0.05). The overexpression of hsa_circ_0001776+miR-1265 mimic group had (128±15) and (133±8) cell clones, (623±10) and (310±7) migrating cells, (643±16) and (420±7) invading cells, (66.39±4.46)% cell migration rate and (68.60±3.53)%, were higher than those of the hsa_circ_0001776+miR-NC group [(86±7) and (80±16), (380±11) and (115±5), (152±7) and (94±4), respectively, (31.41±5.91)% and (30.94±0.67)%, all P＜0.05]. The apoptotic rates in the overexpression of hsa_circ_0001776+miR-1265 mimic group were (19.27±0.15)% and (11.53±0.75)%, respectively, both lower than those in the overexpression of hsa_circ_0001776+miR-NC group [(27.77±1.29)% and (18.43±0.71)%, both P＜0.05]. The results of the subcutaneous tumorigenesis assay in nude mice showed that the volume of tumors in the overexpression of hsa_circ_0001776 group was lower than that in the circ-NC group ( P＜0.05). Conclusion:hsa_circ_0001776 is downregulated in lung squamous cell carcinoma, and hsa_circ_0001776 can inhibit the development of lung squamous cell carcinoma by targeting miR-1265.

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

OBJECTIVE To explore the effects of 5，10-methylenetetetrahydrofolate reductase （MTHFR） gene polymorphism on the adverse reactions in patients with osteosarcoma after the first high-dose methotrexate （HD-MTX） treatment. METHODS A prospective study was conducted to include 53 patients with osteosarcoma treated with HD-MTX at the first admission in General Hospital of Eastern Theater Command. The dose of MTX was evaluated according to the polymorphism of rs1801133 in the METHFR gene and demographic factors， then whole pharmaceutical monitoring was conducted. The data on liver toxicity， renal toxicity， hematological toxicity， and gastrointestinal reaction were collected after the first chemotherapy cycle. Single factor analysis and binary Logistic regression analysis were used to analyze the correlation between MTX dose， 24 h blood drug concentration， and rs1801133 locus genotype with four adverse reactions. RESULTS The MTX dosage in patients with CC wild type was significantly higher than that in TT mutant type （7.97 g/m2 vs. 6.98 g/m2， P＝0.030）， but this difference did not affect the 0 h and 24 h blood drug concentrations of MTX. The above four adverse reactions were not related to the dose of MTX. The results of binary Logistic regression analysis showed that carrying one T allele increased the risk of developing hematological toxicity by 4.13 times（95% confidence interval：1.35-12.62，P＝0.013）. When 24 h plasma concentration threshold of MTX was set to 2.65 µmol/L， the sensitivity and specificity of predicting liver function damage were 53.33% and 86.96%， respectively； when the threshold was set to 7.28 μmol/L， the sensitivity and specificity of predicting renal damage were 100% and 81.63%. CONCLUSIONS The polymorphism of the rs1801133 in the MTHFR gene is associated with hematological toxicity of MTX. Patients who take HD-MTX for the first time and carry the T allele have a high risk of hematological toxicity. The 24 h plasma concentration of MTX is related to liver toxicity and renal toxicity. In addition， monitoring the 24 h blood drug concentration can predict liver and renal toxicity， and take early intervention.

Ruxolitinib， a small molecule inhibitor， selectively targets Janus kinase （JAK） by competitively binding to adenosine triphosphate on the catalytic site of the JAK1 and JAK2 domain， thereby inhibiting JAK activation and signal transducer and activator of transcription （STAT） phosphorylation and prevents the expressions of the JAK-STAT signaling pathway. Oral ruxolitinib has demonstrated promising efficacy for myelofibrosis and polycythemia vera. The topical Ruxolitinib cream， approved by the US FDA as the first non-segmental vitiligo home treatment drug， is set to be launched in domestic medical pioneer areas in August 2023 and is expected to bring about a breakthrough in the treatment of vitiligo. Clinical cases have also shown that Ruxolitinib cream has significant curative effects on atopic dermatitis， alopecia areata， and other conditions， indicating great application prospects.

OBJECTIVE To investigate the effect mechanism of Gualou guizhi granule on neurological function and synaptic plasticity in rats with cerebral ischemia-reperfusion injury. METHODS The rats were randomly divided into sham operation group， model group and Gualou guizhi granule group （3.6 g/kg）， with 6 rats in each group. The cerebral ischemia-reperfusion injury model was established by the suture occlusion method. Two hours after modeling， the model rats were given relevant medicine or normal saline intragastrically， once a day， for 7 consecutive days. After the last medication， the neurological function of rats was evaluated [calculated by modified neurological severity scores （mNSS） and corner turning percentage]； the neuronal apoptosis rate of brain histiocyte in the ischemic side of rats was detected in each group； the positive expressions of growth associated protein 43 （GAP43） and microtubule associated protein 2 （MAP2） were detected； protein expressions of neuron-specific nuclear protein （NeuN）， synaptophysin-1 （Syn-1）， postsynaptic density protein-95 （PSD-95）， peroxisome proliferators-activated receptor γ （PPARγ）， brain-derived neurotrophic factor （BDNF） and tropomyosin receptor kinase B （TrkB）， as well as mRNA expressions of NeuN， Syn-1 and PSD-95 were detected. RESULTS Compared with the model group， mNSS， corner turning percentage and neuronal apoptotic rate were decreased significantly in Gualou guizhi granule group （P＜0.01）； GAP43 represented weak immunoreactivity， and MAP2 represented moderate immunoreactivity； protein expressions of NeuN， Syn-1， PSD-95， PPARγ， BDNF， TrkB and mRNA expressions of Syn-1， NeuN， PSD-95 were all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Gualou guizhi granule can promote synaptic plasticity by activating BDNF/TrkB signaling pathway， thus playing a protective role in cerebral ischemia-reperfusion injury in rats.

In recent years, the incidence of obesity has been rapidly increasing, greatly elevating the incidence of hypertension, heart disease, non-alcoholic fatty liver disease, and other diseases. Reducing the incidence of obesity has become the focus of global concern. There is an urgent need to find effective and safe treatment method. More and more evidence support the efficacy of auricular acupoint therapy for obesity. It has the advantages of safety, effectiveness, convenience, and cheap. This article intends to discuss the research status of auricular acupoint therapy for obesity based on theoretical development, mechanism exploration, and technical innovation in order to promote the clinical application of auricular acupoint therapy for obesity. At present, with the help of multiple disciplines, inheriting and enriching the theoretical connotation of auricular point therapy for obesity, confirming its clinical effectiveness and safety, clarifying its effect mechanism in the treatment of obesity, and improving the traditional auricular acupoint therapy are feasible directions to promote auricular point therapy in the treatment of obesity, and it can make auricular point therapy have a broader application prospect.

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.