[Efficacy evaluation of short-term personalized vestibular rehabilitation in the treatment of acute unilateral vestibulopathy].

Objective: To explore the efficacy and effective node of short-term personalized vestibular rehabilitation (ST-PVR) in treating acute unilateral vestibulopathy (AUVP). Methods: A randomized controlled trial was carried out. The AUVP patients who were admitted to the First Affiliated Hospital of Zhengzhou University from July 2022 to March 2023 were selected and randomized to the vestibular rehabilitation (VR) group and control group via computer-generated randomization. Standard care was the medical treatment with betahistine and prednisolone. Meanwhile, the VR group received ST-PVR. All the patients completed the baseline assessment and underwent follow-up assessments at 1 month and 3 months after the treatment. The assessments were consisted of spontaneous nystagmus (NYS), Romberg test (ROM), head thrust test (HTT), visual analogue scale (VAS) for vertigo, dizziness handicap inventory scale (DHI), activities-specific balance confidence scale (ABC), caloric test using video-electronystagmograph (VNG), and video-head impulse test (vHIT). The measurement data that did not conform to normal distribution were represented by M (Q1, Q3). Generalized estimating equation (GEE) was used to analyze the influence of the ST-PVR on the values of these clinical indicators and the VR grading score. The values of clinical indicators and the VR grading score were compared between the two groups at each follow-up point. Results: Seventy-one AUVP patients were included, with 35 cases in the VR group [14 males and 21 females, aged 51 (33, 55) years] and 36 cases in control group [17 males and 19 females, aged 46 (34, 59) years]. There were statistically significant differences in the impact of ST-PVR on the values of clinical indicators between the two groups (ABC: ß=10.89, P<0.001; VAS: ß=-1.64, P<0.001; DHI: ß=-8.70, P<0.001; NYS: ß=26.73, P<0.001; vHIT: ß=1.41, P=0.047; the VR grading score: ß=1.03, P=0.045). The assessments of the VR group in the positive rate of NYS [14.3% (5/35) vs 50.0% (18/36), P<0.001], ROM [48.6% (17/35) vs 55.6% (20/36), P<0.001], directional preponderance (DP) [34.3% (12/35) vs 75.0% (27/36), P<0.001] and DHI [26 (22, 32) vs 36 (30, 60), P=0.001] were significantly lower than that of the control group at 1 month after the treatment. The results showed a statistically significant difference in ABC [88 (80, 90) vs 76 (61, 88), P<0.001], VAS [2 (1, 3) vs 3 (2, 5), P<0.001] at 3-months after the treatment. The VR grading score of the VR group was improved significantly than those of the control group at 1 month after treatment [21 (17, 21) vs 16 (13, 20), P=0.001]. Conclusion: ST-PVR could improve the results of clinical indicators and VR grading score of the AUVP patients effectively after 1 month of the systematical treatment, and alleviate the symptoms and signs of dizziness in the acute phase as early as possible.

[Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes].

Objective: To investigate the molecular etiology of Perrault syndrome by analyzing the clinical phenotype and pathogenic gene variants of 2 male patients with bilateral severe sensorineural deafness. Methods: Two male patients with Perrault syndrome characterized by severe sensonrineual deafness adimitted to the First Affiliated Hospital of Zhengzhou University between February 2021 and March 2022 were selected, and the clinical phenotype and pathogenic gene variants of them and their family members were summarized. The whole exome sequencing technology was used to screen the pathogenic variants of the probands, and the candidate variants were determined by combining with clinical phenotype. The probands and their family members were verified by the Sanger sequencing method. Results: The whole exome sequencing results showed that the proband of family 1 had a compound heterozygous variants of the LARS2 (NM_015340.4) gene c.1565C>A (p.Thr522Asn) and c.1079T>C (p.Ile360Thr). The reported pathogenic variant c.1565C>A came from the mother, and the novel variant c.1079T>C came from the father. The second proband harbored compound heterozygous variants of HARS2 gene (NM_012208.4) c.1273C>T (p.Arg425Trp) and c.1403G>C (p.Gly468Ala), with the former from the proband's mother, the latter from the father. The c.1273C>T was novel and c.1403G>C was the reported pathogenic variant. All above variants were respectively classified as pathogenic, uncertain significance, uncertain significance and likely pathogenic based on the ACMG guidelines. Conclusion: This study expands the mutational spectrum of LARS2 and HARS2 genes, which highlights that genetic testing plays an important role in the early diagnosis of syndromic deafness.

[Branchio-oto-renal syndrome or branchio-oto syndrome: the clinical and genetic analysis in five Chinese families].

Objective: To screen the causative genes of five families with branchio-oto-renal syndrome (BORS) or branchio-oto syndrome(BOS) and to analyze the phenotypic characteristics and clinical management strategies of patients. Methods: Five families with BORS/BOR from December 2018 to September 2021 were recruited, information of patients, including family history and medical history, was collected, and genealogies were drawn. The examinations concerning audiology, nephrology, and radiology were performed on the affected individuals. Peripheral blood was obtained for DNA extraction, then next-generation sequencing technology was used to screen candidate variants associated with BORS/BOS. Based on patient's clinical results, the appropriate interventions were recommended and implemented. Results: Eight individuals were diagnosed with BOS or BORS. Of the eight patients, all had hearing loss, preauricular pits and ear malformations, and only four presented with branchial cleft fistulae or cysts. Except for two patients(5-I-2, 5-II-2) who did not undergo renal examination, the remaining six lacked renal abnormalities. Genetic analysis identified four likely pathogenic or pathogenic EYA1 variants (c.1715G>T, c.1140+1G>A, c.639G>C, c.1475+1G>C; NM_000503.6), and c.1715G>T was first reported in this study. Middle ear ossicular reconstruction was performed in 1-II-2,2-I-2 and 3-II-2, but did not yield the expected results; then hearing aids and cochlear implantation were recommended and achieved satisfactory results. Conclusions: Next-generation sequencing technology facilitates the diagnosis and genetic counseling of BORS/BOS. Hearing loss, preauricular pits, ear malformations and branchial cleft fistulae or cysts are the most common manifestations of patients in this study. Middle ear surgeries for improving hearing loss may have some limitations in BORS/BOS patients, and hearing aids and cochlear implantation can contribute to hearing gains.

Mechanisms of Toxicity and Cardiotoxicity of Alcohol Extract from Root, Stem and Leaf of Chloranthus Serratus.

ABSTRACT: Objective To compare the differences of cardiotoxicity of alcohol extract from root, stem and leaf of Chloranthus serratus in the rats, and discuss preliminarily its mechanism of toxicity. Methods Rats were randomly divided into four groups: blank, root alcohol, stem alcohol and leaf alcohol, with 8 in each group. After 14 days of continuous intragastric administration, the body mass change curves were drawn. The cardiac coefficient was calculated. The contents of creatine kinase （CK）, creatine kinase isoenzyme （CK-MB）, lactate dehydrogenase （LDH） and α-hydroxybutyrate dehydrogenase （α-HBDH） as well as the content changes of oxidative stress indexes - total superoxide dismutase （T-SOD） and malondialdehyde （MDA） in the serum of rats were detected. The cardiac pathomorphology changes in the rats were observed. The expression of intercellular adhesion molecule （ICAM-1） and heme oxygenase （HO-1） in myocardial tissue was detected. Results Body mass growth rate： stem alcohol group was the smallest, followed by leaf alcohol group. The difference of cardiac coefficient of every group had no statistical significance （P>0.05）. The myocardial tissues of stem alcohol group suffered the most serious damage, followed by the leaf alcohol group. The contents of CK, CK-MB, LDH and α-HBDH in stem alcohol group increased （P<0.05）. The increase of MDA content and decrease of T-SOD content in stem alcohol group had statistical significance compared with the blank group and root alcohol group, while the leaf alcohol group only had statistical significance in the decrease of T-SOD content compared with the blank group （P<0.05）. The positive expression of ICAM-1 enhanced and the expression of HO-1 protein decreased in every group after the intervention of different extracts. The change trend was stem alcohol > leaf alcohol > root alcohol group. Conclusion The alcohol extract from the stem has the highest cardiotoxicity, followed by the leaf extract, and its mechanism of toxicity may be related to oxidative stress.

Overexpression of PER3 reverses paclitaxel resistance of prostate cancer cells by inhibiting the Notch pathway.

OBJECTIVE: To investigate the levels of period circadian protein homolog 3 (PER3) in paclitaxel-resistant prostate cancer patients and the effect of PER3 on paclitaxel-resistant prostate cancer cell lines. PATIENTS AND METHODS: A total of 38 patients diagnosed with prostate cancer in our hospital from June 2013 to June 2016 were divided into paclitaxel-resistant group (n=19) and non-resistant group (n=19) according to the follow-up treatment effects. Fluorescent quantitative polymerase chain reaction (PCR) was performed to evaluate the levels of PER3 in drug-resistant and non-resistant groups as well as the relative levels of PER3 before and after treatment. PER3 was overexpressed or knocked down in a paclitaxel-resistant prostate cancer cell line, followed by measuring its IC50 as well as changes in cell cycle and apoptosis. Using Western blot, we detected downregulation of Notch pathway and related receptor proteins when PER3 was overexpressed. RESULTS: The results of fluorescence quantitative PCR showed that the expression of PER3 in the paclitaxel-resistant prostate cancer group was lower than that in the non-resistant group, and the relative expression of PER3 was decreased after treatment. Fluorescent quantitative PCR and Western blot showed that the expression of PER3 in paclitaxel-resistant prostate cancer cells was higher than that of the untreated counterparts. After overexpression of PER3 by transfecting prostate cancer-resistant cell lines with plasmids, the IC50 was significantly reduced, the cell cycle was arrested, and the apoptosis was significantly increased. Subsequently, we detected decreased expression of Notch1 in PER3 over-expressed paclitaxel-resistant cell lines by Western blot; this attenuated resistance in paclitaxel-resistant cell lines. CONCLUSIONS: PER3 can induce sensitivity of paclitaxel-resistant cell lines to paclitaxel by inhibiting the expression of Notch1.

[Prediction of round window visibility in cochlear implantation with temporal bone high resolution computed tomography].

Objective: To discuss the prediction of round window(RW) visibility in cochlear implantation(CI) with temporal bone high resolution computed tomography(HRCT). Methods: From January 2013 to January 2017, 130 cases underwent both HRCT and CI in our hospital were analyzed. The distance from facial nerve to posterior canal wall(FWD), the angle between facial nerve and inner margin of round window(FRA), and the angle between facial nerve and tympanic anulus to inner margin of round window(FRAA) were detected at the level of round window on axial temporal bone HRCT. A line parallel to the posterior wall of ear canal was drawn from the anterior wall of facial nerve at the level of round window on axial temporal bone HRCT and its relationship with round window was detected (facial-round window line, FRL): type0-posterior to the round window, type1-between the round window, type2-anterior to the round window. Their(FWD, FRA, FRAA, FRL) relationships with intra-operative round window visibility were analyzed by SPSS 17.0 software. Results: FWD(F=18.76, P=0.00), FRA(F=34.57, P=0.00), FRAA (F=14.24, P=0.00) could affect the intra-operative RW visibility significantly. RW could be exposed completely during CI when preoperative HRCT showing type0 FRL. RW might be partly exposed and not exposed when preoperative HRCT showing type1 and type2 FRL respectively. Conclusion: FWD, FRA, FRAA and FRL of temporal bone HRCT can predict intra-operative round window visibility effectively in CI surgery.

[Possible reasons for cerebrospinal fluid gusher in cochlear implantation with inner ear abnormality].

Objective: To discuss the possible reasons for cerebrospinal fluid (CSF) gusher in cochlear implantation (CI) with inner ear abnormality. Method: A retrospective analysis was performed on 340 cases who underwent CI from January 2013 to December 2016 in Division of Otology, Otorhinolaryngology Hospital, the First Affiliated Hospital of Zhengzhou University. Among them, 96 cases had inner ear abnormalities. Imaging examinations were performed on these patients, and classification of inner ear malformation was done according to the results. Results: Among the cases with inner ear abnormality, 9.4% (9/96) suffered from CSF gusher during CI. The inner ear abnormalities were found to be as follows: 3 cases had incomplete partition type Ⅰ; 1 case had incomplete partition type Ⅰ with semicircular canal dysplasia; 1 case had common cavity deformity; 1 case had enlarged vestibular aqueducts and common cavity deformity; 2 cases had Mondini deformity. All of these cases had bony defect in the fundus of the internal acoustic meatus observed on CT scans. Another case was type 1 cochlear aqueduct with round window aplasia. Conclusions: Defects in the modiolus or fundus of the internal acoustic meatus is the main reason for CSF gusher during CI. A patent cochlear aqueduct is another possible reason.

[Pathologic response and changes of serum VEGF during chemoradiotherapy may predict prognosis in non-surgical patients with esophageal carcinoma].

OBJECTIVE: To observe the pathological response in the tumor tissue and the changes of serum level of vascular endothelial growth factor (VEGF) in esophageal cancer patients receiving concurrent chemoradiotherapy, in order to study the impacts of these two factors on the prognosis of patients. METHODS: One hundred pathologically confirmed esophageal cancer patients were treated with radiotherapy including 72 patients with concurrent chemoradiotherapy. After 4 weeks, gastroscopy was performed to collect tumor biopsies for examination of pathological changes. The responses to radiotherapy were classified into three degrees: mild, moderate and intensive. Moreover, serum samples were collected from the patients prior to, at the fourth week during radiotherapy, and one week after radiotherapy, and serum VEGF level was determined. The changes of serum VEGF were classified as increased, unchanged and decreased. Serum samples from 30 healthy subjects were collected and represented as VEGF healthy control. RESULTS: Among the eighty-nine patients evaluable, the 1- and 3-year overall survival (OS) rates were 70.8% and 33.3%, respectively; 1-year and 3-year progression-free survival (PFS) rates were 61.8% and 28.2%, respectively; and 1-year and 3-year local control (LC) rates were 76.9% and 50.0%, respectively. The 1-year OS rates in the patients with mild, moderate and intensive pathological responses were 50.0%, 76.9% and 78.0%, respectively. The 1-year OS rate in the mild response group was significantly lower than that in the intensive response group (P<0.05). The 1-year and 3-year PFS rates in the three groups were 36.4%, 73.1%, 68.3%, and 0.0%, 40.0% and 38.9%, respectively, showing that the rate in the mild response group was significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The PFS rate in the mild response group was significantly lower than that in the moderate and intensive response groups(P<0.05 for both). Moreover, the 1-year local control (LC) rates in the three groups were 52.9%, 83.3% and 83.8%, and the three-year LC rates were 0.0%, 64.3% and 64.0%, respectively, showing that the lowest LC rates in the mild response group were significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The average serum VEGF levels in the patients prior to, during and after radiotherapy were (109.6±33.7) ng/L, (101.2±24.3) ng/L and (99.5±22.9) ng/L, respectively, all significantly higher than that in the healthy subjects [(79.6±39.2) ng/L, P<0.05 for both]. The level of serum VEGF was decreased during and after radiotherapy compared with that before radiotherapy (F=6.124, P=0.004). The 1-year OS rates in the VEGF-increased, unchanged and decreased groups were 50.0%, 67.4% and 86.7%, respectively, and the 3-year OS rates in these three groups were 15.4%, 27.0% and 50.0%, respectively. The OS rates in the increased group were significantly lower than that in the VEGF-decreased group (P<0.05). Moreover, the 3-year PFS rates in the three groups were 7.7%, 21.6% and 46.4%, respectively, and the rate in the VEGF-increased group was significantly lower than that in the VEGF-decreased group (P<0.05). The multi-variate analysis showed that TNM stage, pathological response and serum VEGF were independent factors affecting the survival in the non-surgical patients with esophageal cancer (P<0.05 for all). CONCLUSIONS: Tumor tissue pathological response and variation of serum VEGF level in response to chemoradiotherapy can be used to predict the efficacy of chemoradiotherapy in non-surgical patients with esophageal cancer. Hence, monitoring the pathological response and VEGF changes during the course of therapy is of utmost importance to evaluate and perform an individualized therapy in clinical practice.

[Cortical auditory evoked potentials in congenital hearing impaired children with cochlear implants].

OBJECTIVE: By investigating the auditory cortical evoked potential in congenital hearing impaired children with cochlear implants, the association between central auditory development and the age of implantation was studied. METHODS: P1-N1-P2 were recorded in 110 profound hearing impaired children, aged from 12 to 80 months old and being implanted with cochlear implants before the age of 5 years. Their implant using time ranged from just at the switch-on to 48 months. The stimuli were /m/, /t/, /g/, presented at 65 dB SPL in sound field. The presence rate of each wave was obtained and the relationship between P1 latency and implant age, the time of speech processor switch-on were analyzed. RESULTS: The presence rate of P1, N1 and P2 was 66.4%, 15.5% and 12.7%, respectively. The presence of P1 was significantly higher than that of N1(χ(2)=228.542, P=0.00)and P2(χ(2)=257.438, P=0.00). There was no significant difference of P1 presence rate elicited by /m/, /t/ and /g/(64.1%, 66.9% and 68.3%, χ(2)=0.589, P=0.75). There existed no significant difference either among P1 latency(P=0.22)or amplitude(P=0.09) elicited by /m/, /t/ and /g/. There was significant difference between the implant age before and after 42-month-old regarding the proportion that entered the age-appropriate normal P1 latency range(P=0.02). No significant difference was found among groups of implant using time of 1, 2, 3 and 4 years in aspect of the proportion that entered the age-appropriate normal P1 latency range(P=1.00). CONCLUSIONS: Compared with implanted after the age of 42-month-old children with prelingual hearing impairment younger than 5 years old, the ones implanted before 42-month-old have more chance for normal development for central auditory system. Once implanted before 42-month-old, the cortical auditory system restored its normal development as early as 1 year after implantation.

Clinical application of carbon nanoparticle lymph node tracer in the VI region lymph node dissection of differentiated thyroid cancer.

The application and clinical significance of carbon nanoparticle lymph tracer in the VI region (central region) lymph node dissection of differentiated thyroid cancer was investigated. Eighty patients with differentiated thyroid cancer were equally divided into the carbon nanoparticle-marked group (ipsilateral thyroid injection) and the control group (no injection). All patients underwent standard primary tumor treatment and VI lymph node dissection. The number of lymph nodes retrieved in the carbon nanoparticle group (mean=6.725 pieces, range=1-13) was significantly higher than those retrieved in the control group (mean=3.6, range=1-7; P<0.05). The black staining lymph node rate was 69.89%. A significantly higher number of lymph nodes less than 2 mm were detected in the carbon nanoparticle group (P=0.0023). The transfer rates and lymph node metastasis rates did not differ significantly between the two groups. The black-staining lymph node metastasis rate was 20.74% (39/188) and the non-staining lymph node metastasis rate was 22.22% (18/81), which were not significantly different (P=0.7856). No parathyroid accidental resection was observed in the carbon nanoparticle group, whereas three cases occurred in the control group (P=0.2405). In conclusion, carbon nanoparticles show good lymphatic tracer effects, easy identification, increased number of lymph nodes retrieved, more accurate reflection of the VI region lymph node status, and increased accuracy of the clinical stage. These results should help develop reasonable surgery programs and follow-up comprehensive treatments, and can help to reduce the risk of accident parathyroid resection.

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients.

Albuminuria is an independent predictor of renal and cardiovascular complications in hypertensive subjects. We previously showed that lectin-like oxidized low density lipoprotein receptor 1 (OLR-1) polymorphisms at G501C are associated with susceptibility to essential hypertension and serum C-reactive protein levels. We have now investigated a possible association between OLR-1 polymorphisms at G501C, genotyped by PCR-RFLP, and severity of albuminuria in 307 hypertensive Chinese subjects and 225 age- and sex-matched controls. Urine albumin concentration /urine creatinine concentrations (ACR) were measured to evaluate the severity of albuminuria. Hypertensive subjects had a significantly higher frequency of the CC genotype and the C allele of the OLR-1 polymorphism than controls; this was also true for . hypertensive subjects with macroalbuinuria and microalbuminuria compared to those with normoalbuminuria. The mean ACR levels and mean serum C-reactive protein levels in CC carriers were significantly higher than in GG and GC carriers. There was a significant, positive correlation between serum hs-C-reactive protein levels and ACR levels. We conclude that OLR-1 polymorphisms at G501C affect the severity of albuminuria in essential hypertension patients.

The development of a VR-based treatment planning system for oncology.

In this study, an oncology treatment planning system was developed by integrating the techniques of computer graphics, virtual reality (VR) and three dimensional (3D) image reconstruction. The virtual treatment room was constructed according to the real space, and the 3D data of patient's body was reconstructed from computer tomography (CT) slices in order to provide the 3D clinical information to compare with the therapy in real world. In addition, the virtual multi-leaf collimator (MLC) was constructed to simulate and visualize both the radiation and irradiation fields. All objects in the system had been scaled down according to the true size. The system can be expected to save the preparation time and can be used for teaching and training prior to a real therapy.