BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Objective:To investigate the clinical characteristics and treatment outcomes of patients with blast-induced hearing loss（BIHL）. Methods:The clinical features, laboratory parameters, audiometric profiles, and treatment efficacy of patients with blast induced hearing loss and those with idiopathic sudden hearing loss（ISHL） were analyzed using t-tests, Wilcoxon rank-sum tests, and chi-square tests, with a significance level set at P<0.05. Results:A total of 59 patients in the BIHL group and 117 patients in the ISHL group were included in this study. The mean age of the BIHL group was（39.07±14.49） years, comprising 45 males and 14 females. After the blast, 21 patients went to the hospital within the initial 14-day period, and an additional 38 patients seeking admission thereafter. In the BIHL group, 33 patients had unilateral hearing loss with PTA of （50.30±28.85） dB HL, while 26 had bilateral hearing loss with a PTA of（44.54±26.22） dB HL. In comparison, among the ISHL group, 112 patients had unilateral hearing loss with a PTA of（56.28±14.19） dB HL, and 5 had bilateral involvement with a PTA of（56.25±35.14） dB HL. The effective treatment rate within 14 days for the BIHL group was 31.8%, while for the ISHL group, the effective rate within 14 days was 77.0%. Conclusion:Blast-induced hearing loss is caused by exposure to high-intensity noise. The overall treatment effectiveness during hospitalization is lower compared to idiopathic sudden hearing loss, and the treatment window is shorter. Therefore, greater emphasis should be placed on prevention.
Humans ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; Blast Injuries/therapy* ; Treatment Outcome ; Hearing Loss, Sudden/etiology* ; Adolescent ; Hearing Loss, Noise-Induced/diagnosis*

OBJECTIVES: To compare the efficacy of toric implantable collamer lens (Toric-ICL) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction in patients with moderate to high myopia complicated with astigmatism. METHODS: We retrospectively collected data from 64 patients (aged 18-42 years) with moderate to high myopia complicated with astigmatism (128 eyes) undergoing either Toric-ICL (28 patients/56 eyes) or FS-LASIK (36 patients/72 eyes) at our department between January, 2019 and December, 2020. The changes of uncorrected distance visual acuity (UCVA), spherical equivalent (SE), mean astigmatism correction index (CI), corneal endothelial cell density (ECD) and intraocular pressure (IOP) following the procedures were compared between the two groups. RESULTS: In FS-LASIK group, all the eyes (72/72) achieved an UCVA≥1.0, similar to the rate in Toric-ICL group (55/56 eyes; P=0.2374). The postoperative SE was also comparable between FS-LASIK and Toric-ICL groups [0.43±0.06 D (range: -1.0 to 1.50 D) vs 0.38±0.05 D (range: -0.75 to 1.00 D); P=0.56]. The mean astigmatism CI was significantly higher in FS-LASIK group than in Toric-ICL group (0.8561 vs 0.7176; P<0.0001), and 88.89% of the eyes in FS-LASIK group and 69.64% in Toric-ICL group had postoperative astigmatism ≤0.50 D. No significant changes were observed in postoperative corneal ECD in FS-LASIK group, whereas ECD decreased significantly after the procedure in Toric-ICL group (P=0.0057). The patients undergoing Toric-ICL exhibited no significant changes of postoperative IOP, but the patients receiving FS-LASIK had significantly reduced IOP after the procedure (P<0.001). CONCLUSIONS Although the patients included in Toric-ICL group had higher myopia and astigmatism, Toric-ICL still showed better predictability and efficacy for astigmatic correction in Toric-ICL group. Toric-ICL is an effective and safe equivalent of FS-LASIK for correcting moderate myopia but can be more advantageous for correcting high myopia with astigmatism.
Humans ; Astigmatism/complications* ; Myopia/complications* ; Keratomileusis, Laser In Situ/methods* ; Retrospective Studies ; Adult ; Visual Acuity ; Adolescent ; Young Adult ; Treatment Outcome ; Male ; Lens Implantation, Intraocular/methods* ; Female ; Phakic Intraocular Lenses ; Intraocular Pressure

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

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

Objective:To compare the differences between the variation interpretation standards and guidelines issued by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 (The 2015ACMG/AMP guideline) and the Deafness Specialist Group of the Clinical Genome Resource (ClinGen) in 2018 for hereditary hearing loss (Healing loss, HL) issued the expert specification of the variation interpretation guide (The 2018 HL-EP guideline) in evaluating the pathogenicity of OTOF gene variation in patients with auditory neuropathy. Methods:Thirty-eight auditory neuropathy patients with OTOF gene variant were selected as the study subjects (23 males and 15 females, aged 0.3-25.9 years). Using whole-genome sequencing, whole exome sequencing or target region sequencing (Panel) combined with Sanger sequencing, 38 cases were found to carry more than two OTOF mutation sites. A total of 59 candidate variants were independently interpreted based on the 2015 ACMG/AMP guideline and 2018 HL-EP guideline. Compared with the judgment results in 2015 ACMG/AMP guideline, the variants interpreted as lower pathogenic classifications in the 2018 HL-EP guideline were defined as downgraded variants, and the variants regarded as higher pathogenic classifications were defined as upgraded variants. Statistical analysis was conducted using SPSS 20.0. Results:The concordance rate of variant classification between the guidelines was 72.9%(43/59). The 13.6%(8/59) of variants were upgraded and 13.6% (8/59) of variants downgraded in the classifications of the 2018 HL-EP guideline. A couple of rules saw significant differences between the guidelines (PVS1, PM3, PP2, PP3 and PP5). The distribution of pathogenicity of splicing mutation was statistically different ( P=0.013). Conclusions:The 2018 HL-EP guideline is inconsistent with the 2015 ACMG/AMP guideline, when judging the pathogenicity of OTOF gene variants in patients with auditory neuropathy. Through the deletion and refinement of evidence and the breaking of solidification thinking, the 2018 HL-EP guideline makes the pathogenicity grading more traceable and improves the credibility.

Pressure injury (PI) not only reduces the quality of life of patients but also is expensive to manage, placing a heavy financial burden on patients and their families, and society. Despite the increasing diversity of methods used to identify early PI, there are still few methods that can truly and accurately predict early PI. The sub-epidermal moisture scanner is the first U.S. Food and Drug Administration-authorized PI management device that can predict the occurrence and development of PI by measuring the level of local tissue bio-capacitance and monitoring the tissue viability. As an emerging diagnostic instrument, the sub-epidermal moisture scanner has already shown great advantages in clinical practice, which can promote the informatization, digitization, and intelligent prevention and management of PI. This paper introduces the pathophysiological mechanism of PI, elucidates the working principle and parameter settings of the sub-epidermal moisture scanner, its clinical application in monitoring tissue viability in early PI, and its limitation, and looks forward to its future development.

Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

BACKGROUND: Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples. METHODS: From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR. RESULTS: We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes ( MLH1 , MSH2 , MSH6 , and PMS2 ). CONCLUSION MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.
Humans ; Microsatellite Instability ; Colorectal Neoplasms/diagnosis* ; Microsatellite Repeats/genetics* ; DNA Mismatch Repair