Objective:The purpose of this study was to investigate the characteristics of distortion product otoacoustic emissions (DPOAE) in patients with auditory neuropathy (AN). The factors affecting DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate of first and last diagnosis in the natural course were analyzed.Methods:The sample was obtained from the Multicenter Study on Clinical Diagnosis and Intervention of AN (registration number: ChiCTR2100050125), and the diagnostic criteria for AN were based on the Chinese Clinical Practice Guidelines of Auditory Neuropathy (version 2022). Patients with bilateral AN who underwent 2 or more DPOAE tests were screened and divided into infant groups (≤3 years old) and non-infant groups (>3 years old) according to the age of detection, and the trend of DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate in the natural course of disease were analyzed, in order to explore the relevant influencing factors.Results:A total of 165 patients (330 ears) with AN were included in the study. The overall DPOAE elicitation rate per ear was 77.0%±29.4% at the initial diagnosis and 65.1%±35.2% at the final diagnosis, with a reduction observed in the elicitation rate of 171 ears (51.82%). In the infant group, there were 49 cases (98 ears), including 28 males and 21 females, whose found age ranged from 0 to 3 years old, with a median age of 0.7 years. DPOAE elicitation rate per ear was 57.9%±35.5% in the initial diagnosis, and 32.4%±32.1% in the final diagnosis, with a reduction observed in the elicitation rate of 69 ears (70.41%). In the non-infant group, there were 116 cases (232 ears), including 59 males and 57 females, ranging in found age from 3.9 to 40 years old, with a median age of 14 years old. DPOAE elicitation rate per ear was 84.6%±23.4% in the initial diagnosis, and 78.3%±27.1% in the final diagnosis, with a reduction observed in the elicitation rate of 102 ears (43.97%). Age was found to be correlated with DPOAE changes by multicategorical unordered logistic regression analysis ( B=-0.224, OR=0.799, P<0.001). Conclusions:The elicitation rate of DPOAE in AN patients decreases or even disappears with increasing disease duration; The rate of DPOAE extraction is found to be lower in infant patients with auditory neuropathy (AN) compared to non-infant AN patients. Additionally, it is observed that the decrease in DPOAE extraction rate is more pronounced in infant AN patients as the disease progressed, as compared to non-infant AN patients. DPOAE and cochlear microphonic potentials should be fully combined for accurate diagnosis, and regular follow-up should be conducted to understand the natural course of the disease and give personalized guidance and assistance.

Objective:The purpose of this study was to analyze the clinical characteristics of auditory neuropathy (AN) patients with normal hearing or mild hearing loss.Methods:Data from Multicenter Study on Clinical Diagnosis and Intervention of Acoustic Neuropathy (registration number: ChiCTR2100050125). According to the Chinese clinical practice guideline of auditory neuropathy (version 2022), these patients divided into two groups: the normal hearing group (PTA Normal, PTA N group, the average hearing threshold<20 dB HL) and the mild hearing loss group (PTA Mild hearing loss, PTA M group, the average hearing threshold between 20-35 dBHL). The audiology characteristics, clinical features, and follow-up were analyzed. Data analysis was conducted using GraphPad Prism 8 and SPSS 20.0 software. Results:A total of 75 AN with normal hearing or mild hearing loss were included in this study. The PTA N group consisted of 19 patients (38 ears), including 12 males and 7 females. The average onset age was (16.9±4.5) years old, while the test age was (22.1±5.8) years old for PTA N group. The PTA M group consisted of 56 patients (112 ears), including 29 males and 27 females. The average onset age was (16.2±7.9) years old, while the test age was (23.9±9.0) yeas old for PTA M group. The average hearing threshold of low frequency (0.125-0.5 kHz) was significantly decreased. ABR disappeared in 86.00% (126/150) of the patients. The speech recognition rate was 71.80±22.44% in the PTA N group and 58.08±29.28% in the PTA M group.-SP/AP was 0.98±0.47 in the PTA N and 1.07±0.63 in PTA M group; 40 (53.33%) patients had tinnitus. 29 patients (58 ears) were followed up, including 10 patients (20 ears) in the PTA N group and 19 patients (38 ears) in the PTA M group. There was no significant change in hearing threshold in short-term follow-up (<3 years). With the extension of the disease duration (>3 years), the PTA N group tended to decrease at low frequency, and the PTA M group decreased at high frequency first. The hearing threshold at 0.25 kHz in the PTA N group and 4 kHz in the PTA M group decreased significantly. Conclusions:AN patients with normal hearing or mild hearing loss exhibit abnormal results in audiological examination results, including ABR, electrocochleography and speech discrimination score. A combination of audiological tests should be used to make the diagnosis of AN. With the progression of the disease, AN with normal hearing or mild hearing loss tends to decrease.

Objective:To evaluate the effects of different concentrations of ropivacaine on the growth and migration of lung cancer cells.Methods:Human lung adenocarcinoma cell strain A549 cells and human lung squamous cell strain H520 cells were divided into 4 groups ( n=24 each) using a random number table method: control group (group C) and different concentrations of ropivacaine groups (Ⅰ-Ⅲ groups). Cells were commonly cultured in group C. Ropivacaine 3, 5 and 7 mmol/L were added and then the cells were cultured in Ⅰ-Ⅲ groups, respectively. The cell survival rate was determined using the CCK-8 method at 24, 48 and 72 h of treatment (T 1-3). The cell cycle and apoptosis were detected at T 1 using flow cytometry. The expression of Cyclin D1, cyclin-dependent kinase 4 (CDK4), cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and cleaved caspase-3 was detected using Western blot. Wound healing assay was used to measure cell migration distance. The activities of RhoA and Rac1 were detected by microplate spectrophotometry. Results:The cell viability of A549 and H520 cells sequentially decreased at T 1-3, the proportion of G0/G1 phase and apoptosis sequentially increased, the expression of Cyclin D1 and CDK4 was down-regulated sequentially at T 1, the expression of cleaved PARP-1 and cleaved caspase-3 was up-regulated sequentially, and the cell migration distance, RhoA, and Rac1 activity decreased sequentially in C, Ⅰ, Ⅱ and Ⅲ groups ( P<0.05). Conclusions:Ropivacaine can inhibit the growth and migration ability of lung cancer cells in a concentration-dependent manner, which is related to induction of cell cycle arrest and apoptosis.

This study aimed to investigate the protective effect and underlying mechanism of Mailuo Shutong Pills(MLST) on posterior limb swelling caused by femur fracture in rats. The rats were randomly divided into a sham operation group, a model group, a low-dose MLST group(1.8 g·kg~(-1)·d~(-1)), a high-dose MLST group(3.6 g·kg~(-1)·d~(-1)), and a positive drug group(60 mg·kg~(-1)·d~(-1) Maizhiling Tablets). The femur in the sham operation group was exposed and the wound was sutured, while the other four groups underwent mechanical damage to cause femur fracture. The rats were treated with corresponding drugs by gavage 7 days before modeling and 5 days after modeling, while those in the sham operation group and the model group were given an equivalent dose of distilled water by gavage. Hematoxylin-eosin(HE) staining was used to detect the pathological injury of the posterior limb muscle tissues in rats, and the degree of hind limb swelling was measured. The enzyme-linked immunosorbent assay(ELISA) kit was used to detect the expression levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in the serum of rats in each group. The activity of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and glutathione peroxidase(GSH-Px) in rat serum was also measured. Western blot was used to detect the protein expression levels of heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), and nuclear transcription factor E2-related factor 2(Nrf2) in rat posterior limb muscle tissues. The changes in the intestinal flora and intestinal metabolites in rats were detected by 16S rDNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), respectively, to explore the underlying mechanism of MLST in treating posterior limb swelling caused by femur fracture in rats. Compared with the model group, MLST significantly improved the degree of posterior limb swelling in rats, reduced the levels of serum inflammatory factors, and alleviated oxidative stress injury. The HE staining results showed that the inflammatory infiltration in the posterior limb muscle tissues of rats in the MLST groups was significantly improved. Western blot results showed that MLST significantly increased the protein expression of HO-1, NQO1, and Nrf2 in rat posterior limb muscle tissues compared with the model group. The 16S rDNA sequencing results showed that MLST improved the disorder of intestinal flora in rats after femur fracture. The UPLC-MS/MS results showed that MLST significantly affected the bile acid biosynthesis and metabolism pathway in the intestine after femur fracture, and the Spearman analysis confirmed that the metabolite deoxycholic acid involved in bile acid biosynthesis was positively correlated with the abundance of Turicibacter. The metabolite cholic acid was positively correlated with the abundance of Papilibacter, Staphylococcus, and Intestinimonas. The metabolite lithocholic acid was positively correlated with Papilibacter and Intestinimonas. The above results indicated that MLST could protect against the posterior limb swelling caused by femur fracture in rats. This protective effect may be achieved by improving the pathological injury of the posterior limb muscle, reducing the expression levels of inflammatory and oxidative stress-related factors in serum, reducing the oxidative injury of the posterior limb muscle, improving intestinal flora, and balancing the biosynthesis of bile acids in the intestine.
Rats ; Animals ; NF-E2-Related Factor 2/metabolism* ; Gastrointestinal Microbiome ; Chromatography, Liquid ; Multilocus Sequence Typing ; Tandem Mass Spectrometry ; Oxidative Stress ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Femur ; Bile Acids and Salts ; DNA, Ribosomal ; Superoxide Dismutase/metabolism*

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis, closely associated with the immune system. Its pathogenesis is currently not clear. The lack of specificity in the clinical manifestations and histopathological changes of PG leads to a long clinical diagnosis cycle and even misdiagnosis, which is easy to delay treatment or promote the deterioration of ulcer wound. The diagnosis of this disease is still very difficult, which poses a great challenge to wound repair practitioners. This article reviews the research advances on the pathophysiology, clinical features, and diagnosis of PG in recent years, with the aim of providing reference for relevant clinical practitioners.
Humans ; Pyoderma Gangrenosum/pathology*

Primary ureteral plasmacytoid carcinomas is a rare tumor with high grade and poor diagnosis. Pathological and immunohistochemical staining play an extremely key role in diagnosis since there is no specific clinical and radiological evidence. The surgical removement is the first line treatment. Herein, we report a case of ureteral plasmacytoid carcinoma that was well controlled with multimodal therapy.

Gallbladder Diseases ; Gallbladder Neoplasms ; Humans ; Polyps

BACKGROUND: The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD. METHODS: A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency. RESULTS: In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P  = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785). CONCLUSIONS: As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD. TRIAL REGISTRATION chictr.org.cn, No. ChiCTR-TRC-12003513.
Angina Pectoris ; China ; Coronary Artery Disease/drug therapy* ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Humans

According to the classification of traditional Chinese medicine syndromes of coronavirus disease 2019 by the national competent authority, this study determined that human coronavirus 229 E(HCoV-229 E) was infected in a mouse model of cold and dampness syndrome, so as to build the human coronavirus pneumonia with pestilence attacking lung syndrome model. The model can simulate the traditional Chinese medicine treatment of common disease syndromes in Coronavirus Disease 2019 Diagnosis and Treatment Program(the sixth edition for trial). Specific steps were as follows. ABALB/c mouse model of cold and dampness syndrome was established, based on which, HCoV-229 E virus was infected; then the experiment was divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), high-dose Chaiyin Particles group(8.8 g·kg~(-1)·d~(-1)), and low-dose Chaiyin Particles group(4.4 g·kg~(-1)·d~(-1)). On the day of infection, Chaiyin Particles was given for three consecutive days. Lung tissues were collected the day after the last dose, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted, and the HCoV-229 E virus load was detected by Real-time fluorescent quantitative RT-PCR. Blood leukocytes were separated, and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted, and IL-6, IL-10, TNF-α and IFN-γ contents were detected by ELISA. High and low-dose Chaiyin Particles significantly reduced the lung index(P<0.01) of mice of human coronavirus pneumonia with pestilence attacking the lung syndrome, and the inhibition rates were 61.02% and 55.45%, respectively. Compared with the model control group, high and low-dose Chaiyin Particles significantly increased cross blood CD4~+ T lymphocytes, CD8~+T lymphocytes and total B lymphocyte percentage(P<0.05, P<0.01), and reduced IL-10, TNF-α and IFN-γ levels in lungs(P<0.01). In vitro results showed that TC_(50), TC_0, IC_(50) and TI of Chaiyin Particles were 4.46 mg·mL~(-1), 3.13 mg·mL~(-1), 1.12 mg·mL~(-1) and 4. The control group of in vitro culture cells had no HCoV-229 E virus nucleic acid expression. The expression of HCoV-229 E virus nucleic acid in the virus control group was 1.48×10~7 copies/mL, and Chaiyin Particles significantly reduced HCoV-229 E expression at doses of 3.13 and 1.56 mg·mL~(-1), and the expression of HCoV-229 E nucleic acid was 9.47×10~5 and 9.47×10~6 copies/mL, respectively. Chaiyin Particles has a better effect on the mouse model with human coronavirus pneumonia with pestilence attacking the lung syndrome, and could play a role by enhancing immunity, and reducing inflammatory factor expression.
Animals ; Coronavirus 229E, Human ; Coronavirus Infections ; immunology ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Lung ; immunology ; virology ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred BALB C

Objective:To explore the clinical features and pathogenic mechanisms of a special syndrome with congenital sensorineural hearing loss, albinism, heterochromia iridis, nystagmus and myelin dysplasia.Methods:Detailed medical history, systematic audiology tests, ophthalmic and neurological examinations were carried out to analyze the clinical features of the child, and further molecular genetic tests including chromosome karyotype analysis, and deafness gene screening were conducted.Results:A new de novo heterozygous mutation (c.336G>T/p.Met112Ile) was detected in the child, while both his parents were demonstrated to be wild-type and symptom free. The analysis of clinical features indicated the diagnosis of PCW syndrome. Conclusion:This study identified a new mutation of SOX10 gene, which enriched the mutation spectrum of this gene. And the analysis of clinical characteristics of this patient also expanded the phenotype of this gene. This study provided a reference for clinical diagnosis and genetic diagnosis of PCW syndrome.