Objective To analyze the clinical features,therapeutic effects and relapse factors of anti-myelin oligodendrocyte glycoprotein-IgG antibody associated diseases(MOGAD)in adult patients.Methods The clinical data of 15 adult patients with MOGAD were retrospectively analyzed.The patients were divided into conventional treatment group and plasma exchange group according to the treatment.The efficacy was analyzed by comparing the scores of mRS and expanded disability status scale(EDSS)before and after treatment.And the patients were divided into single course group and relapse course group according to the course of disease,and the relapse-related factors were analyzed.Results There were 10 patients in the conventional treatment group and 5 patients in the plasma exchange treatment group,and the mRS and EDSS of the two groups were significantly lower after treatment than those before treatment(all P＜0.05).There were no significant differences in mRS and EDSS scores between the plasma exchange group and the conventional treatment group after treatment(all P＞0.05).There were 11 patients in the unidirectional course group and 4 patients in the relapsing course group.There were no significant differences between the two groups in gender,age,severity of disease,clinical phenotype,antibody titer,and treatment plan in the acute stage(all P＞0.05).The detection rate of OCB in CSF of patients with relapse course was significantly higher than that of patients with single course.The proportion of patients with maintenance oral hormone duration＜6 months in recurrent disease course group was significantly higher than that in single disease course group(all P＜0.05).Conclusions MOGAD patients respond effectively to glucocorticoid pulse therapy and double filtration plasmapheresis during the acute phase,with a favorable prognosis.MOGAD have a risk of recurrence,those who present with encephalitis at the onset,have positive OCB in CSF,and have a shorter duration of oral glucocorticoid maintenance treatment may be more prone to recurrence.Acute-phase treatment with double filtration plasmapheresis may reduce the recurrence rate.

Objective:To assess the sound localization ability of patients with unilateral sudden hearing loss during the early period of treatment, to explore its changing characteristics and to analyze influencing factors.Methods:A total of 22 patients with unilateral sudden sensorineural hearing loss, with onset within 3 days, who were hospitalized at Shandong Provincial ENT Hospital between January and April 2024, were collected in this study. The cohort included 13 males and 9 females, with a mean age of 36.5 years. Among them, 10 suffered in the right ear and 12 in the left ear. Additionally, 15 healthy individuals (8 males and 7 females, mean age 29.2 years) were selected as controls. Pure tone audiometry and sound localization tests were reviewed on the first day, third day, fifth day of admission; the third week after onset, and the pure tone average and the root-mean-square error(RMSE) were used as indicators, respectively. The improvement of the ability of sound localization and pure tone average were assessed by correlation analyses using SPSS, version 27.0, and multiple regression analysis was employed to explore effects that might influence sound localization ability.Results:The pure tone threshold and sound localization ability on the third week of onset were improved compared with those on the initial three instances(the first, third, and fifth days of admission). 9 of the 22 patients (40.91%, 9/22) presented normal sound localization ability whereas their hearing loss had not recurred yet. The Spearman correlation analysis revealed a significant positive correlation between the improvement of sound localization ability and hearing improvement ( r=0.57, P<0.001). Meanwhile, multiple regression analysis showed that hearing threshold was a significant factor for sound localization when there was audible frequency. Vice versa, at this circumstance, ages and vertigo were significant factors. Conclusions:For most of the patients with unilateral sudden hearing loss, ability of sound localization improves with the decrease of hearing threshold. Notably, some patients can restore normal levels of sound localization for white noise, even in the presence of hearing loss at certain frequencies, by relying on binaural acoustic cues provided by residual hearing.

Objective:To evaluate the sound localization ability of patients with different degrees of unilateral conductive hearing loss (UCHL) in quiet and noisy environments, and to explore the changes and characteristics of sound localization.Methods:This was a cross-sectional study. 41 patients with UCHL were hospitalized in Shandong Provincial ENT Hospital from January to April 2024, including 22 males and 19 females, aged 18-55 years old, with an average age of 36.9 years. According to the pure-tone average (PTA) of 500, 1000 and 2000 Hz in the suffered ear, subjects were divided into slight-mild UCHL group (20 numbers) and moderate-moderately severe UCHL group (21 numbers). 21 patients with normal hearing (NH) were enrolled as controls. All subjects were assessed through pure-tone audiometry, horizontal sound localization test (including azimuth identification test in quiet and noisy environments), Chinese edition short form of Spatial Hearing Questionnaire (C-SHQ12) and twelve-item version of Speech, Spatial, and Qualities of Hearing Scale (SSQ12). SPSS, version 26.0, was used for statistical analysis.Results:There were significant differences in the root-mean-square errors (RMSE) of the sound localization azimuth identification test in quiet and noisy environments among the NH group, slight-mild UCHL group, and moderate-moderately severe UCHL group (Quiet: F=29.109, P<0.001; Noisy: F=24.351, P<0.001). This presented statistically marked difference in the RMSEs between the two listening environments in the slight-mild UCHL group ( t=-4.911, P<0.001). There was a statistical difference in the RMSEs between the normal and affected sides of the subjects in the slight-mild UCHL group in the quiet environment ( t=-2.055, P<0.05), but not in the noisy environment. For moderate-moderately severe UCHL subjects, there were no differences in the RMSEs between the quiet and noisy environments ( P>0.05). What’s more，no significant differences were found between normal side and affected side in both environments ( P>0.05). The RMSEs of UCHL patients in quiet and noisy environments were positively correlated with PTA of air-conduction in the suffered ears (Quiet: r=0.681, P<0.001; Noisy: r=0.346, P<0.05). RMSEs in quiet and noisy environments were negatively correlated with the average localization scores in C-SHQ12 (Quiet: r=-0.576, P<0.001, Noisy: r=-0.613, P<0.001) and in SSQ12 (Quiet: r=-0.634, P<0.001, Noisy: r=-0.663, P<0.001). Conclusions:The sound localization ability of UCHL subjects decreased compared with those with normal hearing, and the RMSE gradually increased with the worse of air conduction hearing threshold. The localization ability of UCHL subjects was further reduced in the noisy environment compared with that in the quiet environment. The slight-mild UCHL subjects had better localization performance in the normal ears while worse in the suffered ears, however, when they were in noisy environment or their hearing loss deteriorated, the localization advantage of the normal ears was no longer obvious, and both sides of the subjects presented poor localization performance.

Objective To analyze the clinical features,therapeutic effects and relapse factors of anti-myelin oligodendrocyte glycoprotein-IgG antibody associated diseases(MOGAD)in adult patients.Methods The clinical data of 15 adult patients with MOGAD were retrospectively analyzed.The patients were divided into conventional treatment group and plasma exchange group according to the treatment.The efficacy was analyzed by comparing the scores of mRS and expanded disability status scale(EDSS)before and after treatment.And the patients were divided into single course group and relapse course group according to the course of disease,and the relapse-related factors were analyzed.Results There were 10 patients in the conventional treatment group and 5 patients in the plasma exchange treatment group,and the mRS and EDSS of the two groups were significantly lower after treatment than those before treatment(all P＜0.05).There were no significant differences in mRS and EDSS scores between the plasma exchange group and the conventional treatment group after treatment(all P＞0.05).There were 11 patients in the unidirectional course group and 4 patients in the relapsing course group.There were no significant differences between the two groups in gender,age,severity of disease,clinical phenotype,antibody titer,and treatment plan in the acute stage(all P＞0.05).The detection rate of OCB in CSF of patients with relapse course was significantly higher than that of patients with single course.The proportion of patients with maintenance oral hormone duration＜6 months in recurrent disease course group was significantly higher than that in single disease course group(all P＜0.05).Conclusions MOGAD patients respond effectively to glucocorticoid pulse therapy and double filtration plasmapheresis during the acute phase,with a favorable prognosis.MOGAD have a risk of recurrence,those who present with encephalitis at the onset,have positive OCB in CSF,and have a shorter duration of oral glucocorticoid maintenance treatment may be more prone to recurrence.Acute-phase treatment with double filtration plasmapheresis may reduce the recurrence rate.

Objective:To assess the sound localization ability of patients with unilateral sudden hearing loss during the early period of treatment, to explore its changing characteristics and to analyze influencing factors.Methods:A total of 22 patients with unilateral sudden sensorineural hearing loss, with onset within 3 days, who were hospitalized at Shandong Provincial ENT Hospital between January and April 2024, were collected in this study. The cohort included 13 males and 9 females, with a mean age of 36.5 years. Among them, 10 suffered in the right ear and 12 in the left ear. Additionally, 15 healthy individuals (8 males and 7 females, mean age 29.2 years) were selected as controls. Pure tone audiometry and sound localization tests were reviewed on the first day, third day, fifth day of admission; the third week after onset, and the pure tone average and the root-mean-square error(RMSE) were used as indicators, respectively. The improvement of the ability of sound localization and pure tone average were assessed by correlation analyses using SPSS, version 27.0, and multiple regression analysis was employed to explore effects that might influence sound localization ability.Results:The pure tone threshold and sound localization ability on the third week of onset were improved compared with those on the initial three instances(the first, third, and fifth days of admission). 9 of the 22 patients (40.91%, 9/22) presented normal sound localization ability whereas their hearing loss had not recurred yet. The Spearman correlation analysis revealed a significant positive correlation between the improvement of sound localization ability and hearing improvement ( r=0.57, P<0.001). Meanwhile, multiple regression analysis showed that hearing threshold was a significant factor for sound localization when there was audible frequency. Vice versa, at this circumstance, ages and vertigo were significant factors. Conclusions:For most of the patients with unilateral sudden hearing loss, ability of sound localization improves with the decrease of hearing threshold. Notably, some patients can restore normal levels of sound localization for white noise, even in the presence of hearing loss at certain frequencies, by relying on binaural acoustic cues provided by residual hearing.

Objective:To evaluate the sound localization ability of patients with different degrees of unilateral conductive hearing loss (UCHL) in quiet and noisy environments, and to explore the changes and characteristics of sound localization.Methods:This was a cross-sectional study. 41 patients with UCHL were hospitalized in Shandong Provincial ENT Hospital from January to April 2024, including 22 males and 19 females, aged 18-55 years old, with an average age of 36.9 years. According to the pure-tone average (PTA) of 500, 1000 and 2000 Hz in the suffered ear, subjects were divided into slight-mild UCHL group (20 numbers) and moderate-moderately severe UCHL group (21 numbers). 21 patients with normal hearing (NH) were enrolled as controls. All subjects were assessed through pure-tone audiometry, horizontal sound localization test (including azimuth identification test in quiet and noisy environments), Chinese edition short form of Spatial Hearing Questionnaire (C-SHQ12) and twelve-item version of Speech, Spatial, and Qualities of Hearing Scale (SSQ12). SPSS, version 26.0, was used for statistical analysis.Results:There were significant differences in the root-mean-square errors (RMSE) of the sound localization azimuth identification test in quiet and noisy environments among the NH group, slight-mild UCHL group, and moderate-moderately severe UCHL group (Quiet: F=29.109, P<0.001; Noisy: F=24.351, P<0.001). This presented statistically marked difference in the RMSEs between the two listening environments in the slight-mild UCHL group ( t=-4.911, P<0.001). There was a statistical difference in the RMSEs between the normal and affected sides of the subjects in the slight-mild UCHL group in the quiet environment ( t=-2.055, P<0.05), but not in the noisy environment. For moderate-moderately severe UCHL subjects, there were no differences in the RMSEs between the quiet and noisy environments ( P>0.05). What’s more，no significant differences were found between normal side and affected side in both environments ( P>0.05). The RMSEs of UCHL patients in quiet and noisy environments were positively correlated with PTA of air-conduction in the suffered ears (Quiet: r=0.681, P<0.001; Noisy: r=0.346, P<0.05). RMSEs in quiet and noisy environments were negatively correlated with the average localization scores in C-SHQ12 (Quiet: r=-0.576, P<0.001, Noisy: r=-0.613, P<0.001) and in SSQ12 (Quiet: r=-0.634, P<0.001, Noisy: r=-0.663, P<0.001). Conclusions:The sound localization ability of UCHL subjects decreased compared with those with normal hearing, and the RMSE gradually increased with the worse of air conduction hearing threshold. The localization ability of UCHL subjects was further reduced in the noisy environment compared with that in the quiet environment. The slight-mild UCHL subjects had better localization performance in the normal ears while worse in the suffered ears, however, when they were in noisy environment or their hearing loss deteriorated, the localization advantage of the normal ears was no longer obvious, and both sides of the subjects presented poor localization performance.

This article summarizes Professor Shang Lili's experience in diagnosing and treating recurrent respiratory tract infections(RRTIs)in children based on the theory of"internal deficiency and external injury".Professor Shang believes that children are in the stage of growth and development,with delicate organs and insufficient vital energy,which is called"internal deficiency";external pathogens repeatedly invade the human body,resulting in clinical manifestations of both cold and heat,ultimately damaging the body's qi,blood,essence,and spirit,known as"external injury"."Internal deficiency and external injury"leads to repeated infections of pathogens in children and causes physical and mental distress,affecting their growth and development.The theory of"internal deficien-cy and external injury"emphasizes the influence of internal and external factors on RRTIs in children,reflecting the evolution of patho-genesis and guiding clinical staging treatment.During the acute infection period,the treatment of wind heat syndrome is based on the Xin Liang and Qing San methods,while the treatment of wind cold syndrome is based on the Xin Wen and Kai Bi methods.For the mixed deficiency and excess syndrome,various methods such as attacking,supplementing,harmonizing,and supporting should be used,and treatment should be based on syndrome differentiation,with adjustments made according to the symptoms;during the inter-mittent period of infection,Professor Shang aims to assist the righteous qi,taking into account the upper,middle,and lower Jiao,and adopting treatment principles such as nourishing the lungs,spleen,and kidneys.Professor Shang's experience provides useful ideas and methods for the treatment of RRTIs in children.

Objective:To explore the effect of exosomes released by Mycobacterium tuberculosis ( Mtb) Rv1983-stimulated macrophages on tuberculosis infection and its potential mechanism. Methods:Exosomes (Rv1983-M-Exo) released by macrophages following Mtb Rv1983 stimulation were extracted by hypervelocity centrifugation and then co-cultured with uninfected macrophages. Macrophage activity was detected by prodium iodide (PI) staining. The level of lipid reactive oxygen species (ROS) was detected by lipid peroxidation fluorescence probe. The expression of ferrous ions (Fe 2+ ) and malondialdehyde (MDA) were detected by colorimetry assay. The protein expression of acyl-CoA synthetase long chain family member 4 (ACSL4) in Rv1983-M-Exo was detected by Western blot. Exosomes (Rv1983-M+ siACSL4-Exo) were isolated from Rv1983-stimulated macrophages with interfered ACSL4 expression Rv1983 and co-cultured with uninfected macrophages. The effect of exosomes on the polarization of macrophages was detected by flow cytometry and Western blot. The effects of exosomes on phagocytosis and killing ability of macrophages were analyzed by plate colony assay and BCG-phagocytosis lysosome co-localization assay. Results:Compared with macrophage-derived exosomes (M-Exo), Rv1983-M-Exo promoted ferroptosis in uninfected macrophages, manifested by increased levels of intracellular lipid ROS, MDA and Fe 2+, which were significantly inhibited by ferroptosis inhibitor Fer-1. Rv1983 induced macrophages to release exosomes with high expression of ACSL4. Interfering the expression of ACSL4 in macrophages, the concentration of ACSL4 in the Rv1983-M+ siACSL4-Exo was significantly reduced. When the Rv1983-M+ siACSL4-Exo was co-cultured with uninfected macrophages, the ferroptosis of macrophages was significantly reduced. Rv1983-M-Exo promoted M2 macrophage polarization which showed up-regulation of CD206 and Arg1 expression, and decreased the phagocytosis and killing ability of macrophages, while Rv1983-M+ siACSL4-Exo or Fer-1 in combination with Rv1983-M-Exo reduced the expression of CD206 and Arg1 in macrophages, and promoted the phagocytosis and killing ability. Conclusions:Mtb Rv1983 protein up-regulates the level of ACSL4 in the exosomes secreted by macrophages, thereby inducing ferroptosis in uninfected macrophages, causing M2 polarization of macrophages, weakening phagocytosis and killing ability, and promoting Mtb infection.

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.

Objective:To explore the effect of exosomes released by Mycobacterium tuberculosis ( Mtb) Rv1983-stimulated macrophages on tuberculosis infection and its potential mechanism. Methods:Exosomes (Rv1983-M-Exo) released by macrophages following Mtb Rv1983 stimulation were extracted by hypervelocity centrifugation and then co-cultured with uninfected macrophages. Macrophage activity was detected by prodium iodide (PI) staining. The level of lipid reactive oxygen species (ROS) was detected by lipid peroxidation fluorescence probe. The expression of ferrous ions (Fe 2+ ) and malondialdehyde (MDA) were detected by colorimetry assay. The protein expression of acyl-CoA synthetase long chain family member 4 (ACSL4) in Rv1983-M-Exo was detected by Western blot. Exosomes (Rv1983-M+ siACSL4-Exo) were isolated from Rv1983-stimulated macrophages with interfered ACSL4 expression Rv1983 and co-cultured with uninfected macrophages. The effect of exosomes on the polarization of macrophages was detected by flow cytometry and Western blot. The effects of exosomes on phagocytosis and killing ability of macrophages were analyzed by plate colony assay and BCG-phagocytosis lysosome co-localization assay. Results:Compared with macrophage-derived exosomes (M-Exo), Rv1983-M-Exo promoted ferroptosis in uninfected macrophages, manifested by increased levels of intracellular lipid ROS, MDA and Fe 2+, which were significantly inhibited by ferroptosis inhibitor Fer-1. Rv1983 induced macrophages to release exosomes with high expression of ACSL4. Interfering the expression of ACSL4 in macrophages, the concentration of ACSL4 in the Rv1983-M+ siACSL4-Exo was significantly reduced. When the Rv1983-M+ siACSL4-Exo was co-cultured with uninfected macrophages, the ferroptosis of macrophages was significantly reduced. Rv1983-M-Exo promoted M2 macrophage polarization which showed up-regulation of CD206 and Arg1 expression, and decreased the phagocytosis and killing ability of macrophages, while Rv1983-M+ siACSL4-Exo or Fer-1 in combination with Rv1983-M-Exo reduced the expression of CD206 and Arg1 in macrophages, and promoted the phagocytosis and killing ability. Conclusions:Mtb Rv1983 protein up-regulates the level of ACSL4 in the exosomes secreted by macrophages, thereby inducing ferroptosis in uninfected macrophages, causing M2 polarization of macrophages, weakening phagocytosis and killing ability, and promoting Mtb infection.