Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.

Objective: Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS). Methods: We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS. Results: We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group. Conclusion Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.

Objective: Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS). Methods: We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS. Results: We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group. Conclusion Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.

Objective: Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS). Methods: We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS. Results: We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group. Conclusion Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.

Objective: Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS). Methods: We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS. Results: We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group. Conclusion Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.

Objective:This study aimed to compare the effects of cochlear implantation（CI） on vestibular function in patients with large vestibular aqueduct syndrome（LVAS） and in patients with extremely severe deafness with normal inner ear structure. Methods:A total of 28 LVAS patients and 28 patients with normal inner ear structure who suffered from extremely severe deafness were selected. The parameters of caloric tests, bone conduction evoked cervical vestibular-evoked myogenic potentials（cVEMP）, bone conduction evoked ocular vestibular-evoked myogenic potentials（oVEMP） and video head impulse tests（v-HIT） were compared between the two groups before and after CI. The data were analyzed using SPSS 26.0 software. Results:There was no significant difference in the results of the preoperative caloric test, v-HIT, and oVEMP（P1, N1） between the LVAS group and the control group（P>0.05）. Compared to the control group, the LVAS group exhibited a shorter cVEMP P1[（13.41±0.71）ms vs （16.28±0.89）ms, P<0.000 1], shorter N1[（19.83±0.54）ms vs （28.18±1.56）ms, P<0.000 1], higher amplitude[（123.60±83.80）μV vs （73.92±79.85）μV, P=0.049 4] and higher oVEMP amplitude[（16.60±13.87）μV vs （9.96±10.47）μV, P=0.028 5] before CI. The abnormal rate of caloric test increased in both groups after CI（25.00% vs 57.14%, P=0.028 8, 32.14% vs 82.14%, P=0.000 3, respectively）. There was no significant difference in the v-HIT parameters in both groups before and after the operation. As for the LVAS group, there was no statistically significant difference in cVEMP and oVEMP induction rates before and after operation. In the control group, there was a decrease in cVEMP induction rate（96.42% vs 64.28%, P=0.005 2） and oVEMP induction rate（96.42% vs 57.14%, P=0.000 9） after CI. LVAS group showed a shorter cVEMP P1[（13.41±0.71）ms vs （10.30±0.60）ms, P<0.000 1]; shorter cVEMP N1[（19.86±0.53）ms vs （18.97±1.33）ms, P=0.004 7]; decreased amplitude[（124.50±84.86）μV vs （64.35±61.57）μV, P=0.001 0] and shorter oVEMP amplitude[（15.92±13.03）μV vs （9.16±9.20）μV, P=0.009 9] after CI. The oVEMP N1 in the control group was longer than that before operation[（11.73 ± 0.91）ms vs （13.35 ± 2.60）ms, P=0.019 6], whereas there was no significant difference in other VEMP parameters after CI. Conclusion:Before CI, there was no significant difference in the results of the caloric test and v-HIT between the LVAS group and the control group, but the LVAS group exhibited increased sensitivity to acoustic stimulation-induced myogenic potentials. After CI, the function of the semicircular canal was impaired in both groups in the low-frequency area, and remained largely unaffected in the high-frequency area. Additionally, the function of the otolith in the LVAS group was less affected than that in the control group after CI, which may be related to the fact that the enlarged vestibular aqueduct of the LVAS patients acted as the third window of the inner ear.
Humans ; Vestibular Aqueduct/physiopathology* ; Cochlear Implantation ; Male ; Female ; Vestibular Evoked Myogenic Potentials ; Deafness/physiopathology* ; Child ; Adolescent ; Adult ; Young Adult ; Hearing Loss, Sensorineural/physiopathology* ; Vestibular Function Tests

Objective:To explore the clinical characteristics and treatment methods of middle ear cholesteatoma with intracranial and extracranial complications as the first diagnosis. Methods:A total of 244 patients were initially diagnosed with intracranial and/or extracranial complications associated with middle ear cholesteatoma at the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2022, and medical records were collected and retrospectively analyzed. Results:Among 244 patients with intracranial and extracranial complications of middle ear cholesteatoma, 203 cases had one complication, 34 cases had 2 complications, and 7 cases had 3 or more complications. One hundred and eighty-six cases presented labyrinthitis, 41 cases had peripheral facial paralysis, 27 cases had periauricular abscess, 12 cases had meningitis, 10 cases had brain abscess, 7 cases had sigmoid sinus lesions, 6 cases had epidural abscess, and 4 cases demonstrated hydrocephalus. Conclusion:The destructive nature of middle ear cholesteatoma can lead to intracranial and extracranial complications. The incidence rate of extracranial complications is highest for labyrinthitis. Patients with otitis media who complained dizziness should raise clinical suspicion for potential labyrinthitis. The second most prevalent extracranial complication is peripheral facial paralysis, and early facial nerve decompression surgery is critical for better recovery of facial paralysis symptoms. Brain abscess is the most common intracranial complications, which has the highest fatality rate. Clinicians should be alert to otogenic brain abscess. Otolaryngology and neurosurgery teams should cooperate and evaluate patients' middle ear lesions and brain abscess, and jointly develop personalized treatment plans.
Humans ; Cholesteatoma, Middle Ear/surgery* ; Retrospective Studies ; Facial Paralysis/etiology* ; Brain Abscess/diagnosis* ; Male ; Female ; Otitis Media/complications* ; Meningitis/etiology* ; Labyrinthitis/etiology* ; Adult ; Middle Aged ; Young Adult

Objective:X-linked non-syndromic hearing loss is an extremely rare type of hearing impairment. This study conducted a phenotypic and genetic analysis of a family with X-linked dominant inheritance to explore the causes of hearing loss. Methods:Clinical data were collected from a patient with non-syndromic hearing loss who visited the Otorhinolaryngology Department of the First Affiliated Hospital of Zhengzhou University in June 2023. Phenotypic and genetic analyses were performed on family members, including audiometric tests, whole-exome sequencing, and PCR-Sanger sequencing verification. Audiological assessments comprised pure-tone audiometry, impedance audiometry, auditory brainstem response, and otoacoustic emission tests. Results:The affected individuals in this pedigree have X-linked dominant non-syndromic deafness caused by mutations in the SMPX gene. The proband, along with their mother and maternal grandmother, exhibit varying degrees of sensorineural hearing loss. Whole-exome sequencing revealed a novel pathogenic variant, NM_014332.3: c. 133-2A>C, in the SMPX gene in the proband. Sanger sequencing confirmed that the proband, proband's mother, and grandmother all carried this pathogenic variant. Conclusion:This study reports a novel pathogenic variant in the SMPX gene, providing additional medical evidence for the diagnosis and treatment of X-linked dominant inherited non-syndromic hearing loss. It enriches the mutation spectrum of the SMPX gene.
Humans ; Pedigree ; Mutation ; Phenotype ; Male ; Hearing Loss, Sensorineural/genetics* ; Exome Sequencing ; Female ; Adult ; Hearing Loss/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Muscle Proteins

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.