Severe iron-deficiency anemia after short-term moderate consumption of green tea in woman: A rare case report.

While the mechanisms by which tea consumption hinders iron absorption are well understood, tea-related anemia usually stems from prolonged and excessive intake, which obstructs iron absorption and depletes the body's iron reserves. Consequently, it is uncommon for hemoglobin levels to plummet by 6.9 g/dl solely due to moderate tea consumption over a span of three months. We present a case of severe iron-deficiency anemia in a woman following short-term, moderate green tea consumption. After modifying her tea intake regimen, there was no recurrence of anemia. Clinicians should be mindful that even moderate tea consumption can precipitate severe iron-deficiency anemia in individuals particularly vulnerable to its effects on iron absorption.

[Test-retest reliability of subjective visual vertical from different head-tilt angles in young healthy adults].

Objective:To establish the normal values of subjective visual vertical （SVV） in different head deflection angles and analyze its test and retest reliability, in order to provide a reference for the clinical application of SVV in the evaluation of vestibular disorders. Methods:Thirty-one healthy young people were selected to wear VR glasses, and the SVV data were tested in five different head-tilt, namely, 0° in the upright head position, 45°in the left head position, 45° in the right head position, 90° in the left head position, and 90° in the right head position, and were re-tested 2 weeks later. Results:①The mean values of SVV at 5 different head-tilt angles of 0°, left 45°, right 45°, left 90°, and right 90° were -0.07±1.71, 4.30±5.39, -6.51±5.58, -3.76±7.42, and 0.40±8.02, respectively, The 95% confidence limits of SVV at 0°, left 45°, right 45°, left 90°, right 90°, and right 90° were （-3.42, 3.28）, （-6.26, 14.86）, （-17.45, 4.43）, （-18.30, 10.78）, and（-15.32, 16.12）, respectively; ②The absolute values of SVV at 4 different head-tilt angles of left 45°, right 45°, left 90°, and right 90° were 5.62±3.96, 6.90±5.07, 6.82±4.70 and 6.48±4.68, respectively. The 95% confidence limits of SVV at left 45°, right 45°, left 90°, right 90°, and right 90° were（0，12.11）,（0，15.21）,（0，14.53）and（0，14.16）, respectively. The asymmetry ratio is 10% for the absolute value of the 45 ° deviation and 3% for the absolute value of the 90° deviation; ③Intra-class correlation coefficients（ICC） for 0°, left 45°, right 45°, left 90°, right 90°were 0.757, 0.673, 0.674, 0.815, and 0.856, respectively. Conclusion:SVV has good retest reliability and high stability, and the SVV normal value data of different head deviation angles established in the present study can be used as a reference for the diagnosis and evaluation of vestibular disorders.

Endoscopic treatments for rectal neuroendocrine tumors: a systematic review and network meta-analysis.

BACKGROUND: Conventional endoscopic mucosal resection (cEMR), EMR with a transparent cap, EMR using a ligation device (EMR-L), EMR after circumferential precutting (EMR-P), and endoscopic submucosal dissection (ESD) have been used for resecting rectal neuroendocrine tumors (r-NETs). However, there is no consensus regarding which is the best treatment. This study aimed to compare the outcomes of the aforementioned 5 techniques for resecting r-NETs by network meta-analysis. METHODS: Electronic databases (PubMed, Cochrane Library, Embase, Ovid Medline, and Web of Science) were systematically searched to include relevant studies published from inception to September 1, 2023. The en bloc resection rate, histologic complete resection rate, positive lateral margin rate, positive vertical margin rate, adverse events rate, and procedure time were compared. RESULTS: A total of 27 studies with a total of 2112 r-NETs were included, and the mean diameter of tumors was 6.24 mm. Pairwise meta-analysis showed that EMR-L and ESD had higher en bloc resection and histologic complete resection rates and lower positive vertical margin rate than those of cEMR in resecting r-NETs. Compared with ESD, EMR-L and EMR-P achieved similar resection rates and significantly shortened the procedure time without increasing adverse events. The network meta-analysis evaluated the surface under the cumulative ranking curves and revealed that EMR-L was the best modality for treating r-NETs considering the comprehensive results of the en bloc resection rate, histologic complete resection rate, positive lateral margin rate, positive vertical margin rate, adverse events rate, and procedure time. CONCLUSION: EMR-L should be recommended as the first-line endoscopic treatment for small r-NETs.

Iron metabolism and ferroptosis in nonalcoholic fatty liver disease: what is our next step?

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with increasing prevalence worldwide. NAFLD could develop from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), NASH-related fibrosis, cirrhosis, and even hepatocellular carcinoma. However, the mechanism of NAFLD development has not yet been fully defined. Recently, emerging evidence shows that the dysregulated iron metabolism marked by elevated serum ferritin, and ferroptosis are involved in the NAFLD. Understanding iron metabolism and ferroptosis can shed light on the mechanisms of NAFLD development. Here, we summarized studies on iron metabolism and the ferroptosis process involved in NAFLD development to highlight potential medications and therapies for treating NAFLD.

Characteristics of vestibular migraine, probable vestibular migraine, and recurrent vertigo of childhood in caloric and video head impulse tests.

Objective: Vertigo is very common in children, but the specific diagnosis and characteristics are not clear. The main objective of this study was to analyze the characteristics of caloric test (CT) and video head impulse test (vHIT) in vestibular migraine of childhood (VMC), probable vestibular migraine of childhood (PVMC), and recurrent vertigo of childhood (RVC), which can provide a reference value for their clinical diagnosis. Methods: We selected VMC, PVMC and RVC patients under 18 years of age from the outpatient Department of Otolaryngology-Head and Neck Surgery between May 2021 and August 2022. All patients underwent vestibular function examinations, including eye movement recording CT and vHIT. CT results depended on whether both canal paresis and directional preponderance were under normal limits, and vHIT results depended on the gain values of vestibulo-ocular reflex. The results of both tests were analyzed according to the disease type. Results: Among the 81 pediatric vertigo patients aged 5-17 years, 44 were females and 37 were males. According to the type of vertigo, 29 patients (25.80%) were diagnosed with VMC, 11 (13.58%) with PVMC, and 41 (50.62%) with RVC. The abnormal rates of the CT in VMC, PVMC, and RVC patients were 24.14%, 36.36%, and 17.07%, respectively. There was no significant difference in the abnormal rates among the three groups (P > 0.05). None of the patients showed abnormal vHIT results (all abnormal rates 0.00%). The abnormal CT rates were significantly higher than those of abnormal vHIT rates (P < 0.05). Conclusions: VMC, PVMC, and RVC are more likely to be diagnosed by symptoms, as neither CT nor vHIT are specific to any conditions. Due to different clinical presentations of vertigo in pediatric patients, it is critical to further clarify the diagnosis with medical history and clinical characteristics.

Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy.

PURPOSE: Development of B-cell lymphoma 2 (BCL-2)-specific inhibitors poses unique challenges in drug design because of BCL-2 homology domain 3 (BH3) shared homology between BCL-2 family members and the shallow surface of their protein-protein interactions. We report herein discovery and extensive preclinical investigation of lisaftoclax (APG-2575). EXPERIMENTAL DESIGN: Computational modeling was used to design "lead" compounds. Biochemical binding, mitochondrial BH3 profiling, and cell-based viability or apoptosis assays were used to determine the selectivity and potency of BCL-2 inhibitor lisaftoclax. The antitumor effects of lisaftoclax were also evaluated in several xenograft models. RESULTS: Lisaftoclax selectively binds BCL-2 (Ki < 0.1 nmol/L), disrupts BCL-2:BIM complexes, and compromises mitochondrial outer membrane potential, culminating in BAX/BAK-dependent, caspase-mediated apoptosis. Lisaftoclax exerted strong antitumor activity in hematologic cancer cell lines and tumor cells from patients with chronic lymphocytic leukemia, multiple myeloma, or Waldenström macroglobulinemia. After lisaftoclax treatment, prodeath proteins BCL-2‒like protein 11 (BIM) and Noxa increased, and BIM translocated from cytosol to mitochondria. Consistent with these apoptotic activities, lisaftoclax entered malignant cells rapidly, reached plateau in 2 hours, and significantly downregulated mitochondrial respiratory function and ATP production. Furthermore, lisaftoclax inhibited tumor growth in xenograft models, correlating with caspase activation, poly (ADP-ribose) polymerase 1 cleavage, and pharmacokinetics of the compound. Lisaftoclax combined with rituximab or bendamustine/rituximab enhanced antitumor activity in vivo. CONCLUSIONS: These findings demonstrate that lisaftoclax is a novel, orally bioavailable BH3 mimetic BCL-2-selective inhibitor with considerable potential for the treatment of certain hematologic malignancies.

[Compensation effect of hearing aid on speech recognition in noise in patients with unilateral hearing loss].

Objective:The aim of this study was to investigate the speech recognition in noise in patients with unilateral hearing loss（UHL）, and explore the compensation effect of behind-the-ear（BTE） hearing aid on speech recognition in patients with varied degrees of UHL. Methods:Twenty-five participants with UHL were divided into two groups according to the degree of hearing loss: one group included subjects with unilateral moderate and moderately severe hearing loss and another one included subjects with unilateral severe and profound hearing loss. Fifteen healthy subjects with normal hearing were enrolled as the control group. The speech recognition thresholds and speech recognition scores at fixed signal noise ratio（SNR） in UHL participants with and without BTE hearing aid were tested in the sound field and compared with those in the control group. One-way ANOVA was used to examine the significance of the difference between UHL participants and control group, and paired t-test was used to analyze the compensation effect of hearing aid on speech recognition in noise in UHL participants. Results:The speech recognition thresholds were significantly higher in both UHL groups（P<0.01） compared with the control group, there was no significant difference between two UHL groups. And the speech recognition scores were significantly lower when the SNR was fixed（P<0.01）, and there were no significant differences between two UHL groups. When fitting BTE hearing aid, the speech recognition thresholds of the two groups significantly decreased（P<0.01）, and the speech recognition scores significantly improved（P<0.01）. Conclusion:Patients with above moderate UHL presented a significant decrease in performance of speech recognition in noise, and fitting BTE hearing aid on the affected ear had a positive compensation effect.

[To address on the refined and individualized comprehensive evaluation of inner ear function].

Auditory and vestibular function detection technology is the premise and key to the diagnosis and management for inner ear diseases. Concurrent damage to the auditory and vestibular system occurs in many inner ear diseases. The general points and issues on hearing and vestibular function tests, as well as the clinical significance of refined and individualized comprehensive evaluation of inner ear function are described in this paper.

[Gain characteristics of three pairs of semicircular canals in video head impulse paradigm test and suppression head impulse paradigm test in healthy young Chinese population].

Objective:To summarize gain characteristics of three pairs of semicircular canals in head impulse paradigm （HIMP） and suppression head impulse paradigm （SHIMP） in healthy young Chinese population. Methods:HIMP and SHIMP tests were performed on 40 healthy young volunteers enrolled as study group, by using EyeseeCam examiantion system （Interacoustics，Denmark）. The elicitation rates and gain values of the two saccades were recorded, and the gain values were compared and analyzed. Results:The results of 40 healthy young people were as follows: in HIMP, the instantaneous gain at 60 ms of the horizontal semicircular canals were 1.11±0.07 on the left side and 1.08±0.07 on the right side; the regression gain of the horizontal semicircular canals were 1.09±0.06 on the left side and 1.10±0.06 on the right side; the regression gain of the vertical semicircular canals were 1.08±0.12 on the right anterior, 1.07±0.11 on the left posterior, 1.41±0.16 on the right posterior and 1.42±0.16 on the left anterior. So in HIMP, no significant difference could be found between left and right side in both horizontal and vertical semicircular canal conjugate plane regarding regression gain （P>0.05）, except that 60 ms instantaneous gain on the left horizontal semicircular canals was slightly higher than that on the right side （P<0.05）.The instantaneous gain values of the horizontal semicircular canal at 60 ms in SHIMP were 1.08±0.08 on the left side and 1.06±0.07 on the right side; the regression gain in horizontal semicircular canals were 1.06±0.07 on the left side and 1.07±0.06 on the right side, respectively; the regression gains of vertical semicircular canal were 1.06±0.13, 1.08±0.16, 1.49±0.16, 1.39±0.15, on the right anterior, left posterior, right posterior, and left anterior side. So in SHIMP, no significant difference could be found in 60 ms instantaneous gain in horizontal conjugate plane, regression gain in horizontal conjugate plane and regression gain in right anterior left posterior conjugate plane （P>0.05）, while the regression gain of the left anterior right posterior conjugate plane in the right was found slightly higher than that of the left （P<0.05）.Both 60 ms instantaneous gain and regression gain in horizontal conjugate plane in HIMP were slightly higher than that of SHIMP （P<0.05）, while no significant difference could be found in vertical conjugate planes （P>0.05）. In both HIMP and SHIMP tests, gains of the left anterior right posterior conjugate plane was slightly higher than that of both horizontal plane and the right anterior left posterior conjugate plane （P<0.05）, while no significant difference could be found in gains between horizontal and the right anterior left posterior conjugate plane （P>0.05）. Conclusion:Gain values of HIMP and SHIMP were slightly different among different semicircular canals conjugate planes.It is suggested that each examination center should establish normal values for their own and make correction regularly.

[The effect of different rotation modes on testing resulting of the subjective visual vertical].

Objective:To investigate the effect of different rotations modes of control rod on testing results of the subjective visual vertical （SVV）. Methods:Twenty-four normal young volunteers were selected for this study, and the control rod of SVV was rotated in clockwise, counterclockwise and any direction at the head tilt-positions of 0°, 45° left and 45° right. The differences of SVV deflection angle values at different rotation modes were analyzed. Results:①The deviation angle values of SVV obtained by rotating the control rod in clockwise, counterclockwise and any direction at the head tilt-positions of 0° were 1.56°±0.21°, 3.05°±0.24°, and 2.16°±0.22°, respectively，and the difference was statistically significant （P<0.05）,the deviation angle value of SVV in clockwise direction was smaller; ②At head tilt-positions of 45° left, the SVV deviation angle values obtained by rotating the control rod in three rotation modes were 2.59°±0.53°, 4.03°±0.51°, and 3.49°±0.54°, respectively, and the difference was statistically significant（P<0.05）,the deviation angle value in the clockwise direction was also smaller; ③At the head tilt-positions of 45° right, the SVV deviation angle values in three modes were 4.68°±0.58°, 7.23°±0.72°, and 5.93°±0.96°, respectively, and the difference was statistically significant （P<0.05）,the deviation value of SVV was also smaller when rotated in the clockwise direction; ④Comparison of SVV deviation angle values in three rotation modes at the head tilt-positions of 45° left and 45° right showed that there was no statistical difference in clockwise and in any direction （P>0.05）, while the difference was statistically significant when rotated in the counterclockwise direction （P<0.05）. Conclusion:Different rotation modes of the control rod during SVV testing will affect the test results. Rotating the control rod in clockwise direction to make the SVV values more accurate is recommended.

[Correlation between Mandarin acceptable noise level and cortical auditory evoked potential in young normal-hearing listeners].

Objective:To investigate the correlation between Mandarin acceptable noise level （M-ANL） and cortical auditory evoked potential （CAEP）, and to explore the possible mechanism leading to individual differences in M-ANL values. Methods:Thirty listeners aged 22-33 years with normal hearing were selected as the study subjects, and the M-ANL test and CAEP test were performed respectively. The most comfortable level （MCL）, maximum background noise level （BNL）, M-ANL and CAEP values of each subject were recorded. The latency of each wave of P1, N1, P2, N2, P300 and the amplitude of P1-N1, P2-N2, P300 in CAEP were recorded for each subject. SPSS 25.0 was used for statistical analysis to explore the correlation between the MCL value, BNL value and M-ANL values and the latency of P1, N1, P2, N2, P300 and P1-N1, P2-N2, P300 amplitudes of CAEP. Results:①The MCL value and M-ANL value were positively correlated with the P2 latency of CAEP, and the correlation coefficients were 0.404 and 0.400, respectively, and the differences were statistically significant （P<0.05）. There was no correlation with P1, N1, N2, and P300 latencies of CAEP （P>0.05）. ②The MCL value, BNL value and M-ANL value had no significant difference with the CAEP wave amplitudes of P1-N1, P2-N2, and P300 （P>0.05）. Conclusion:There was a certain correlation between M-ANL and CAEP in young adults with normal hearing, suggesting that the central auditory cortex might play a potential regulatory role in the background noise tolerance. Individuals with a greater background noise acceptance might have stronger central efferent mechanisms and/or less active central afferent mechanisms.

The effect of nursing and rehabilitation measures on quality of life and expression of Bax/Bcl2 genes in patients with stroke.

Stroke is the leading cause of neurological problems and the third leading cause of death globally, leading to various neurological defects. Due to the importance of applying nursing and rehabilitation measures to reduce complications in these patients, a study was conducted to determine the effect of nursing and rehabilitation measures on the quality of life of patients with stroke. This two-stage experimental study (before and after) was performed on 20 patients with stroke admitted to the internal medicine department. Patients were selected by sampling method, which had inclusion criteria. Data were collected using a questionnaire based on the quality of life in four areas of physical, mental, general health, and social functioning before and after the intervention. Real-Time PCR measured the expression of Bcl2 / Bax genes. Descriptive and inferential statistics analyzed the data. The results showed that the mean quality of life scores in physical function, psychological, social position, and general health after nursing and rehabilitation measures increased significantly (p = .05). Also, the quality of life score after these measures had a significant increase compared to before (p = .05). Also, a significant increase was observed in the expression ratio of the Bcl2 / Bax genes in the study group compared to the control group, which indicates the effect of nursing and rehabilitation measures on cerebral ischemia. The findings showed that the application of nursing and rehabilitation measures positively affects various aspects of patients' quality of life with stroke. These programs should be provided while educating patients and their families to help them achieve greater independence in the future.

Clinical characteristics of vestibular evoked myogenic potentials in children with recurrent vertigo of childhood.

OBJECTIVE: To explore the possible pathogenesis of recurrent vertigo of childhood (RVC) and the clinical diagnosis value of vestibular-evoked myogenic potentials (VEMPs). METHODS: The clinical data of 19 children (5.95 ± 0.38 years) diagnosed with RVC and 17 normal children (5.35 ± 0.31 years) enrolled in the control (NC) group from April 2017 to February 2021 was collected and analyzed. All subjects were tested for both cervical VEMP (cVEMP) and ocular VEMP (oVEMP). The elicit rate, thresholds, N1 latency, P1 latency, interval, amplitude, and amplitude asymmetry ratio (AAR) of VEMPs were compared and analyzed between the two groups. RESULTS: (1) The elicit rates of cVEMP and oVEMP have no significant difference between the two groups (P > 0.05). (2) The thresholds of cVEMP and oVEMP in the RVC group were higher than that in the NC group (P < 0.05). (3) The N1 latency of cVEMP in the RVC group was longer than that in the NC group (P < 0.05). The P1 latency of cVEMP and latencies of oVEMP have no significant difference between the two groups (P > 0.05). (4) The interval of cVEMP in the RVC group was longer than that in the NC group (P < 0.05), while the interval of oVEMP has no significant difference between the two groups (P > 0.05). (5) The amplitude of cVEMP in the RVC group was higher than that in the NC group (P < 0.05), while the amplitude of oVEMP was similar in the two groups (P > 0.05). (6) The AAR values of oVEMP and cVEMP were similar in the two groups (P > 0.05). CONCLUSIONS: The elicit rates of VEMPs in children with RVC did not differ from that of normal children, but the thresholds were all increased, suggesting reduced sensitivity of the otolith organ and vestibular nerve conduction pathways. The P1 latency of cVEMP was normal in children with RVC, but N1 latency and interval of cVEMP were increased, we finally reached a conclusion that there might be potential impairment in the inferior vestibular nerve and the subsequent nerve conduction pathway in RVC.

Type-1 Grade 2 Multi-Focal Gastric Neuroendocrine Tumors Secondary to Chronic Autoimmune Gastritis.

Background: Chronic autoimmune gastritis (CAG) refers to chronic atrophic gastritis due to autoimmunity. Loss of gastric glands in CAG results in hypergastrinemia and achlorhydria leading to Vitamin B12 deficiency and hyperplasia of G cells and enterochromaffin-like (ECL) cells. Vitamin B12 deficiency could cause pernicious anemia and subacute combined degeneration, while G cells and ECL cells hyperplasia might develop gastric neuroendocrine tumor (G-NET). Case Presentation: A 35-year-old Chinese female presented with multi-focal type-1 Grade 2 (G2) NETs with a 14-year history of pernicious anemia and subacute combined degeneration. Conclusion: Here, we report a rare case of a Chinese patient presenting G-NET combined with pernicious anemia and subacute combined degeneration, which are secondary to chronic autoimmune gastritis. This case also illustrates the importance of routine gastroscopy in patients with Vitamin B12 deficiency.

Discovery of a novel ALK/ROS1/FAK inhibitor, APG-2449, in preclinical non-small cell lung cancer and ovarian cancer models.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and focal adhesion kinase (FAK). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations. METHODS: KINOMEscan® and LANCE TR-FRET were used to characterize targets and selectivity of APG-2449. Water-soluble tetrazolium salt (WST-8) viability assay and xenograft tumorigenicity were employed to evaluate therapeutic efficacy of monotherapy or drug combination in preclinical models of solid tumors. Western blot, pharmacokinetic, and flow cytometry analyses, as well as RNA sequencing were used to explore pharmacokinetic-pharmacodynamic correlations and the mechanism of actions driving drug combination synergy. RESULTS: In mice bearing wild-type or ALK/ROS1-mutant non-small-cell lung cancer (NSCLC), APG-2449 demonstrates potent antitumor activity, with correlations between pharmacokinetics and pharmacodynamics in vivo. Through FAK inhibition, APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by reducing CD44+ and aldehyde dehydrogenase 1-positive (ALDH1+) cancer stem cell populations, including ovarian tumors insensitive to carboplatin. In epidermal growth factor receptor (EGFR)-mutated NSCLC xenograft models, APG-2449 enhances EGFR TKI-induced tumor growth inhibition, while the ternary combination of APG-2449 with EGFR (osimertinib) and mitogen-activated extracellular signal-regulated kinase (MEK; trametinib) inhibitors overcomes osimertinib resistance. Mechanistically, phosphorylation of ALK, ROS1, and FAK, as well as their downstream components, is effectively inhibited by APG-2449. CONCLUSIONS: Taken together, our studies demonstrate that APG-2449 exerts potent and durable antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other therapies. A phase 1 clinical trial has been initiated to evaluate the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK+ NSCLC refractory to earlier-generation ALK inhibitors. TRIAL REGISTRATION: Clinicaltrial.gov registration: NCT03917043 (date of first registration, 16/04/2019) and Chinese clinical trial registration: CTR20190468 (date of first registration, 09/04/2019).

[Myotonia-rectified bone-conducted vibration vestibular evoked myogenic potential in normal adults].

Objective:To study the characteristics of bone-conducted vibration vestibular evoked myogenic potential（BCV-VEMP） in normal adult with and without myotonia rectification, and to provide accurate reference for clinical vestibular function evaluation. Methods:Thirty normal adults（60 ears） aged 20-32 years old were selected to receive BCV-VEMP in a sitting position. BCV-VEMP were induced by B-81 bone-conducted vibrator at 129.5 FL, the P1 latency, N1 latency, P1-N1interval, amplitude, and amplitude asymmetry ratios were recorded in two test conditions. Results:Clear and repeatable waveforms of BCV-cVEMP and BCV-oVEMP were obtained in all normal adults. The P1 and N1 latencies of BCV-cVEMP were（16.00±2.02） ms and（25.04±2.57） ms, respectively, P1-N1 interval was（9.04±1.78） ms. The N1 and P1 latencies of BCV-oVEMP were（10.39±0.81） ms and（15.85±1.00） ms, respectively, iand interval was（5.46±0.86） ms. The amplitudes of BCV-cVEMP and BCV-oVEMP in two test conditions were statistically significant（P<0.05）. The amplitude asymmetry ratios of BCV-cVEMP and BCV-oVEMP after rectification were （17.03±9.14）% and （20.43±11.65）%, respectively. Conclusion:BCV-VEMP is a feasible and reliable tool for vestibular function assessment. The establishment of a normal values such as amplitude and amplitude asymmetry ratio after rectification can provide a more reliable and accurate reference.

Molecular Mechanisms of Isolated Polycystic Liver Diseases.

Polycystic liver disease (PLD) is a rare autosomal dominant disorder including two genetically and clinically distinct forms: autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease (PCLD). The main manifestation of ADPKD is kidney cysts, while PCLD has predominantly liver presentations with mild or absent kidney cysts. Over the past decade, PRKCSH, SEC63, ALG8, and LRP5 have been candidate genes of PCLD. Recently, more candidate genes such as GANAB, SEC61B, and ALR9 were also reported in PCLD patients. This review focused on all candidate genes of PCLD, including the newly established novel candidate genes. In addition, we also discussed some other genes which might also contribute to the disease.

Frequent numerical and structural chromosome changes in early generations of synthetic hexaploid wheat.

Modern hexaploid wheat (Triticum aestivum L.; AABBDD) has evolved from a hybrid of tetraploid wheat (closely related to Triticum turgidum L. ssp. durum (Desf.) Husn., AABB) and goatgrass (Aegilops tauschii Coss., DD). Variations in chromosome structure and ploidy have played important roles in wheat evolution. How these variations occur and their role in expanding the genetic diversity of modern wheat remain largely unknown. Synthetic hexaploid wheat (SHW) can be used to investigate chromosome variations that occur during the early generations of existence. SHW lines derived by crossing durum wheat 'Langdon' with 12 Ae. tauschii accessions were analyzed using oligonucleotide probe multiplex fluorescence in situ hybridization (FISH) of metaphase chromosomes and SNP markers. Cluster analysis based on SNP markers categorizes them into three groups. Among 702 plants from the S8 and S9 generations, 415 (59.12%) carried chromosome variations involving all 21 chromosomes, but with different frequencies for each chromosome and sub-genome. Total chromosome variation frequencies varied between lines, but there was no significant difference among the three groups. The non-random chromosome variations in the SHW lines detected in this study may indicate that similar variations occurred in the early stages of wheat polyploidization and played important roles in wheat evolution.

[Effect of the course of posterior semicircular canal benign paroxysmal positional vertigo on residual symptoms after successful canalith repositioning procedure].

Objective:To investigate the effect of the course of posterior semicircular canal benign paroxysmal positional vertigo（BPPV） on residual symptoms after successful canalith repositioning procedure（CRP）. Methods:A total of 56 patients with posterior semicircular canal BPPV were selected from July 2020 to March 2021. They were divided into the short course group and the long course group according to the duration of disease from symptom onset to CRP treatment. All patients were treated with mechanical Epley repositioning procedure with rotary chair assistance. After successful repositioning treatment, they were followed up for seven to ten days. All patients were assessed using the vertigo disorder scale （DHI） before and after treatment,the differences of each dimension score and total score of DHI before and after successful CRP were compared between these two groups. Results:① After successful CRP, in patients with mild residual symptoms, the ratio between short course group and long course group were 68.6% and 31.4%, respectively. While in patients with moderate to severe residual symptoms,the ratio between short course group and long course group was 20% and 80%, respectively. The difference was statistically significant（P<0.05）. ②Before CRP, there was no significant difference in Physical dimension（DHI-P, 7 items） and in Function dimension（DHI-F, 9 items） between the two groups（P>0.05）, but there was significant difference in Emotion dimension（DHI-E, 9 items） and in total DHI score between the two groups（P<0.05, respectively）. After treatment, there was no significant difference in DHI-P score between the two groups（P>0.05）, but there were significant differences in DHI-F, DHI-E and DHI total score between the two groups（P<0.05,respectively）. Compared with the scores of DHI-P, DHI-F, DHI-E and DHI total score before and after successful CRP, the significant differences were found between the short course group and long course group（P<0.05,respectively）. ③There was no significant difference in the difference of DHI dimensions and total score between the short course group and the long course group before after reduction（P>0.05,respectively）. Conclusion:The duration of posterior semicircular canal BPPV（P-BPPV） does not affect the short-term efficacy of P-BPPV repositioning treatment, but patients with long course of P-BPPV are more likely to have moderate to severe residual symptoms after successful CRP，mainly in social function and emotional psychology.

Discovery of EEDi-5273 as an Exceptionally Potent and Orally Efficacious EED Inhibitor Capable of Achieving Complete and Persistent Tumor Regression.

Embryonic ectoderm development (EED) is a promising therapeutic target for human cancers and other diseases. We report herein the discovery of exceptionally potent and efficacious EED inhibitors. By conformational restriction of a previously reported EED inhibitor, we obtained a potent lead compound. Further optimization of the lead yielded exceptionally potent EED inhibitors. The best compound EEDi-5273 binds to EED with an IC50 value of 0.2 nM and inhibits the KARPAS422 cell growth with an IC50 value of 1.2 nM. It demonstrates an excellent PK and ADME profile, and its oral administration leads to complete and persistent tumor regression in the KARPAS422 xenograft model with no signs of toxicity. Co-crystal structures of two potent EED inhibitors with EED provide a solid structural basis for their high-affinity binding. EEDi-5273 is a promising EED inhibitor for further advanced preclinical development for the treatment of human cancer and other human diseases.