Objective To understand the reliability of caloric test results through the analysis of the pod shape dia-gram types of caloric test and to provide a more accurate and reliable basis for vestibular system function evaluation.Meth-ods The results of caloric test in 528 patients from July 2021 to May 2022 in vertigo diagnosis and treatment center were analyzed.According to pod pattern and unilateral weakness(UW),the patients were divided into five groups:cold and warm test symmetrical group,left and right side asymmetry group,single value significant abnormal group,bilateral hypo-plasia group and pod morphology unable to be classified group.Unreliable data can be identified by comparing,explaining,and summarizing the results of UW of different groups,so as to reduce the interference of unreliable data to clinical diagno-sis and treatment.Results Cold and warm test symmetric group(n=439)included patients with symmetry of bilateral vestibular function(n=273)and decreased vestibular function of one side(n=166).Left and right symmetrical groups in-eluded pationts with bilateral symmetric vestibular function(n=11)and unilateral reduction(n=13).Single value signifi-cant abnormal group showed cases with unilateral vestibular function reduction(n=25)and bilateral symmetric vestibular function(n=11).Bilateral hypolasion group showed cases with bilateral symmetric vestibular function(n=25)and unilat-eral reduction(n=9).Pod morphology unclassified group(n=5)suggested varions interference factors.Conduson When the function of the peripheral vestibular is symmetrical and normal,we should be alert to the existence of temperature effect,and should consider the inspection of the perfusion apparatus and the calibration of the irrigation temperature.When the function of the peripheral vestibular shows unilateral weakness,repeating the irrigation is recommended when the single value of the caloric test significantly increases or decreases.If there is no change,repeating the irrigation at the same tem-perature in the other ear or even repeating the whole caloric test are recommended.The UW value could not truly reflect the state of peripheral vestibular function when the caoric test produces bilateral weakness.Therefore,water irrigation could be used to make a correct judgment based on the medical history and other auxiliary examinations.It is of great significance to judge the effectiveness of caloric test comprehensively by combining the morphology of pod diagram with UW value.

ObjectiveTo investigate the therapeutic effect of Dayuanyin on acute lung injury induced by H1N1 infection and decipher the potential mechanism. MethodThe constituents in Dayuanyin were analyzed by ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry （UHPLC-Q-Exactive Orbitrap MS）. Forty-eight female BALB/c mice were randomized into normal， model， oseltamivir （19.5 mg·kg^-1）， and low-， medium-， and high-dose （2.73， 5.46， 10.92 g·kg^-1） Dayuanyin groups. The normal and model groups were administrated with deionized water by gavage， and the other groups were administrated with the corresponding drugs by gavage. On day 3 of drug administration， the normal group received nasal inhalation of normal saline， and the other groups were inoculated intranasally with A/RP/8/34 （H1N1） for the modeling of influenza virus infection. Mice were administrated with drugs continuously for 7 days and weighed daily. Sampling was performed 12 h after the last administration， and the lung tissue was weighed to calculate the lung index. Hematoxylin-eosin staining was performed to observe the pathological and morphological changes of the lung tissue and bronchi. The cytometric bead array （CBA） was used to measure the serum levels of interferon-gamma （IFN-γ）， C-X-C motif ligand 1 （CXCL1）， tumor necrosis factor-alpha （TNF-α）， chemokine ligand 2 （CCL2）， interleukin-12p70 （IL-12p70）， chemokine ligand 5 （CCL5）， interleukin-1β （IL-1β）， chemokine （C-X-C motif） ligand 10 （CXCL10）， granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin-10 （IL-10）， interferon-beta （IFN-β）， interferon-alpha （IFN-α）， and interleukin-6 （IL-6）. According to the results of mass spectrometry and network pharmacology， we analyzed the mechanism of Dayuanyin in treating acute lung injury caused by H1N1. The protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， nuclear factor-kappa B （NF-κB）， and their phosphorylated forms were determined by Western blot. The mRNA levels of myeloid differentiation factor 88 （MyD88）， Toll-like receptor 3 （TLR3）， Toll-like receptor 7 （TLR7）， and Toll-like receptor 8 （TLR8） in the lung tissue were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultA total of 57 compounds， including paeoniflorin and baicalein， were detected in Dayuanyin. Compared with the normal group， the model group showed decreased body weight （P<0.01）， lung edema and hemorrhage， increased lung index （P<0.01）， and elevated levels of IFN-γ， IL-12p70， CCL5， IL-1β， CXCL10， GM-CSF， IFN-β， and IL-6 （P<0.01）. Compared with the model group， Dayuanyin attenuated alveolar wall thickening， capillary congestion， and immune cell infiltration， reduced the alterations in body weight and lung index （P<0.01）， and down-regulated the protein levels of IFN-γ， IL-12p70， CCL5， IL-1β， CXCL10， GM-CSF， IFN-β， and IL-6 （P<0.01）. A total of 57 key genes were predicted by network pharmacological analysis， of which the MAPK signaling pathway was the main target signaling pathway. Compared with the normal group， the model group showed up-regulation in the protein levels of phosphorylation （p）-ERK1/2， p-p38 MAPK， and p-NF-κB （P<0.01） and the mRNA levels of TLR7， TLR8， MyD88， and TLR3 （P<0.05， P<0.01）. Compared with the model group， Dayuanyin lowered the phosphorylation levels of ERK1/2， p38 MAPK， and NF-κB p65 in a dose-dependent manner （P<0.01） and down-regulated the mRNA levels of TLR3， TLR7， TLR8， and MyD88 （P<0.01）. ConclusionDayuanyin can prevent and control H1N1 infection-induced acute lung injury by inhibiting the TLR/MAPK/NF-κB signaling pathway.

Diabetic ulcer (DU), one of the common and serious complications in patients with diabetes mellitus, often leads to infection, necrosis and amputation, and has a long and costly treatment period. Because of DU's unclear healing mechanism and the difficulty of delayed healing, its treatment and management have been a major challenge in clinical medicine. In recent years, the potential role of mitochondrial autophagy in DU has become a research hotspot with the in-depth study of mitochondrial autophagy mechanism. Previous studies have shown that mitochondrial autophagy is an important intracellular self-repair mechanism that plays a crucial role in maintaining cellular health and functional stability. During the development of DU, mitochondrial autophagy plays multiple roles in attenuating oxidative stress and inflammatory responses, maintaining mitochondrial functional homeostasis, influencing cell proliferation and repair capacity during DU healing, promoting DU healing, and enhancing antimicrobial capacity. In this paper, we illustrate the multiple roles played by mitochondrial autophagy in DU prevention and treatment, as well as the potential applications of mitochondrial autophagy in DU therapy. It is expected to provide a basis for the clinical application of mitochondrial autophagy in DU treatment, and provide more effective strategies and solutions for the treatment of DU.

Diabetic ulcer (DU), one of the common and serious complications in patients with diabetes mellitus, often leads to infection, necrosis and amputation, and has a long and costly treatment period. Because of DU's unclear healing mechanism and the difficulty of delayed healing, its treatment and management have been a major challenge in clinical medicine. In recent years, the potential role of mitochondrial autophagy in DU has become a research hotspot with the in-depth study of mitochondrial autophagy mechanism. Previous studies have shown that mitochondrial autophagy is an important intracellular self-repair mechanism that plays a crucial role in maintaining cellular health and functional stability. During the development of DU, mitochondrial autophagy plays multiple roles in attenuating oxidative stress and inflammatory responses, maintaining mitochondrial functional homeostasis, influencing cell proliferation and repair capacity during DU healing, promoting DU healing, and enhancing antimicrobial capacity. In this paper, we illustrate the multiple roles played by mitochondrial autophagy in DU prevention and treatment, as well as the potential applications of mitochondrial autophagy in DU therapy. It is expected to provide a basis for the clinical application of mitochondrial autophagy in DU treatment, and provide more effective strategies and solutions for the treatment of DU.

SARS-CoV-2 caused severe threat to people's health all over the world,and has attracted widespread attention from researchers.The spike protein of SARS-CoV-2 is a key structure mediating the binding of the virus to its host.Therefore,it is im-portant to elucidate the mechanism of spike protein-induced immune responses.We've reviewed the structure of spike protein from al-pha to omicron variant,as well as the potential mechanisms of spike-induced in multiple systems,so as to provide a reference for dis-ease prevention and treatment.

Extranodal NK/T cell lymphoma, nasal type（ENKTL） is a highly aggressive malignant tumor derived from NK cells. This article reports a case of ENKTL invading the larynx and digestive tract. The clinical clinical manifestations include hoarseness and intranasal masses.
Humans ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Nose/pathology* ; Nose Neoplasms/pathology* ; Larynx/pathology* ; Gastrointestinal Tract/pathology*

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Objective:To investigate the protective effect and potential mechanisms of microRNA-26a-5p (miR-26a-5p) on podocyte injury in diabetic kidney disease (DKD).Methods:(1) In vivo experiment: Four-week-old db/db mice were divided into db/db group, db/db+agomir-NC group and db/db+miR-26a-5p agomir group according to random number table method, with 10 mice in each group, and 10 db/m mice of the same week-old were set as normal control group. At the age of 10 weeks, pathological changes were observed through light and electron microscopy. Kidney weight/body weight (KW/BW), urinary albumin to creatinine ratio (ACR), fasting blood glucose (FBG) and other biochemical indicators were also detected. The position and expression of miR-26a-5p in kidney tissue were determined through fluorescence in situ hybridization and quantitative real-time PCR, while the expressions of transient receptor potential cation channel-6 (TRPC6) and Nephrin in kidney tissue were determined by Western blotting and immunohistochemistry. (2) In vitro experiment: The immortalized mouse podocytes (MPC5) were divided into 5 groups: normal glucose group, high mannitol group, high glucose group, high glucose+miR-26a-5p mimic group, and high glucose+mimic-NC group. The expressions of miR-26a-5p, TRPC6 and Nephrin were detected. Luciferase reporter assay was conducted to research the relationship of miR-26a-5p and TRPC6. Results:(1) In vivo experiment: Compared with db/m group, db/db mice exhibited lower KW/BW and disrupted conditions of ACR, FBG, total cholesterol, triglycerides and low density lipoprotein cholesterol (all P<0.01). Increased glomeruli volume, more extracellular matrix deposition, thicker basement membrane and more foot process fusion were observed by light and electron microscope. Increased expression of TRPC6 protein as well as decreased expression of Nephrin protein and miR-26a-5p were detected in kidney tissues of db/db mice ( P<0.05). Compared with db/db+agomir-NC group, db/db mice transfected by miR-26a-5p agomir exhibited less albuminuria, with less protein expression of TRPC6 and more Nephrin in kidney tissue (all P<0.05). (2) In vitro experiment: Compared with normal glucose group, high glucose-treated podocytes exhibited increased expression of TRPC6 ( P<0.05), as well as decreased expression of Nephrin ( P<0.05) and miR-26a-5p ( P<0.01). Compared with high glucose+mimic-NC group, lower expression of TRPC6 and higher expression of Nephrin were detected in podocytes transfected by miR-26a-5p mimic (both P<0.05). Luciferase reporter assay confirmed that miR-26a-5p could regulate the expression of TRPC6 precisely. Conclusions:The expression of miR-26a-5p in podocytes is down-regulated in the context of high glucose and miR-26a-5p protects podocytes from injury via inhibiting the expression of TRPC6 in DKD.

OBJECTIVE: To summarize the result of genetic testing and therapeutic prospect of 2042 unrelated Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD) from a single center from 2005 to 2019. METHODS: Peripheral blood samples of the pedigrees were collected for the detection of DMD gene variants with combined multiple ligation-dependent probe amplification (MLPA), next generation sequencing (NGS) and Sanger sequencing. RESULTS: DMD and BMD have respectively accounted for 78.60% and 21.40% of the pedigrees, which included 33 female probands. Variants of the DMD gene were detected in 1986 pedigrees (97.26%). Large deletions, duplications and small-scale mutations have respectively accounted for 71.85%, 8.76% and 19.39%. Common deletions and duplications have included deletion of exons 45-50 and duplications of exon 2, while no hot spot was found with small-scale mutations. For 1595 pedigrees affected with DMD, 935 (58.62%) were hereditary and 660 (41.38%) were de novo in origin. 34.28% (700/2042) of the patients had symptoms which could be relieved by gene therapy. CONCLUSION This has been the largest single-center study of DMD pedigrees, which has attained definite diagnosis in 97.26% of the patients. The results have enabled genetic counseling and prenatal diagnosis for the affected families upon their subsequent pregnancies, enriched the spectrum of DMD gene variants, as well as facilitated study of the mechanism of DMD gene mutations and exploration of clinical treatment.
China ; Dystrophin/genetics* ; Exons/genetics* ; Female ; Gene Deletion ; Genetic Testing ; Humans ; Muscular Dystrophy, Duchenne/therapy* ; Mutation ; Pedigree ; Pregnancy

Objective: Microtia is a relatively common birth defect, and its etiology is still unclear. In this paper, Phenolyzer, a kind of phenotype-based gene analyzer, was used to prioritize candidate genes involved in microtia. Methods: The search term " Microtia" was entered in the Phenolyzer interface. Through the steps of disease matching, gene query, gene scoring, seed gene expansion, the genetic information results of microtia were finally generated. This article traced 10 candidate genes in detail. Results: There were 13485 genes associated with microtia or related syndromes, of which 130 were seed genes. Each gene had a corresponding score, and the higher the score, the greater the correlation with the microtia. Among them, the top 10 genes included HOXA2, CHD7, CDT1, CDC6, ORC1, ORC4, ORC6, SMAD4, GLI3 and MED12. Conclusions Phenolyzer provides a detailed summary of candidate genes for microtia, providing accurate research directions for screening high-throughput sequencing results and subsequent studies.