Three novel sesquiterpene polyol esters from the root bark of Celastrus angulatus Maxim and their nitric oxide inhibitory activity.

Three new sesquiterpene polyol ester compounds angulatin V [1ß,15-diacetoxy-2ß-(α-methyl)-butanoyloxy-4α,6α-dihydroxy-8α-isobutanoyloxy-9ß-benzoxy-ß-dihydroagarofuran], angulatin W [1ß,2ß-diacetoxy-4α,6α-dihydroxy-8-carbonyl-9ß-benzoxy-15-isobutanoyloxy-ß-dihydroagarofuran], angulatin X [1ß,2ß,8α-triacetoxy-4α, 6α-dihydroxy-9ß-benzoxy-15-nicotinyl-ß-dihydroagarofuran] (1-3), together with one known compound Putterine B (4), were isolated from the root bark of Celastrus angulatus Maxim. The structures of compounds 1-3 were elucidated by NMR, HRESIMS, IR data, and comparison with the literature data. The anti-inflammatory activity of all compounds was evaluated by measuring nitric oxide production in RAW264.7 macrophages. Compounds 1-4 showed no significant nitric oxide inhibitory activity at 2.5 and 5 µM concentrations.

Pneumocystis jirovecii and Nocardia pneumonia in a middle-aged male with Nephrotic syndrome: a case report and literature review.

INTRODUCTION: Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia. CASE PRESENTATION: A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes. CONCLUSION: The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates.

Factors affecting suboptimal maturation of autogenous arteriovenous fistula in elderly patients with diabetes:A narrative review.

Autogenous arteriovenous fistula (AVF) is considered the preferred vascular access choice for individuals undergoing maintenance hemodialysis (MHD) and is widely utilized in China, as reported by the Dialysis Outcomes and Practice Patterns Study. Despite its popularity, the significant incidence of poor AVF maturation often leads to the need for central venous catheter insertion, increasing the risk of complications like superior vena cava stenosis and catheter-related infections, which in turn raises the overall mortality risk. With the prevalence of diabetes rising globally among the elderly and diabetic kidney disease being a leading cause of end-stage renal disease necessitating renal replacement therapy, our retrospective review aims to explore the various factors affecting AVF maturation in this specific patient population. While there have been numerous studies examining AVF complications in MHD patients, including issues like failure, patency loss, stenosis, thrombosis, poor maturation, and other influencing factors, there remains a gap in large-scale clinical studies focusing on the incidence and risk factors for immature AVF specifically in elderly diabetic patients. This paper delves into the pathophysiological mechanisms, diagnostic criteria, and unique considerations surrounding AVF maturation in elderly diabetic patients, distinguishing them from the general population. Our literature review reveals that elderly diabetic patients exhibit a higher risk of AVF immaturity compared to the general population. Additionally, there exists a continuing discourse regarding several aspects related to this group, including the choice of dialysis access, timing of AVF surgery, and surgical site selection. Furthermore, we delve into the management strategies for vascular access within this specific group with the goal of providing evidence-based guidance for the establishment and maintenance of functional vascular access in elderly diabetic patients.

Causal associations between circulation ß-carotene and cardiovascular disease: A Mendelian randomization study.

The causal association between circulating ß-carotene concentrations and cardiovascular disease (CVD) remains controversial. We conducted a Mendelian randomization study to explore the effects of ß-carotene on various cardiovascular diseases, including myocardial infarction, atrial fibrillation, heart failure, and stroke. Three single nucleotide polymorphisms (SNPs) associated with the ß-carotene levels were obtained by searching published data and used as instrumental variables. Genetic association estimates for 4 CVDs (including myocardial infarction, atrial fibrillation, heart failure, and stroke) in the primary analysis, blood pressure and serum lipids (high-density lipoprotein [HDL] cholesterol, LDL cholesterol, and triglycerides) in the secondary analysis were obtained from large-scale genome-wide association studies (GWASs). We applied inverse variance-weighted as the primary analysis method, and 3 others were used to verify as sensitivity analysis. Genetically predicted circulating ß-carotene levels (natural log-transformed, µg/L) were positively associated with myocardial infarction (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.18, P = .011) after Bonferroni correction. No evidence supported the causal effect of ß-carotene on atrial fibrillation (OR 1.02, 95% CI 0.96-1.09, P = .464), heart failure (OR 1.07, 95% CI 0.97-1.19, P = .187), stroke (OR 1.03, 95% CI 0.93-1.15, P = .540), blood pressure (P > .372) and serum lipids (P > .239). Sensitivity analysis produced consistent results. This study provides evidence for a causal relationship between circulating ß-carotene and myocardial infarction. These findings have important implications for understanding the role of ß-carotene in CVD and may inform dietary recommendations and intervention strategies for preventing myocardial infarction.

Fine particulate matter and its constituent on ovarian reserve: Identifying susceptible windows of exposure.

BACKGROUND: Little is known about the associations of exposure to fine particulate matter (PM2.5) and its constituents with ovarian reserve, and the potential susceptible window of exposure remains unclear. METHODS: We performed a retrospective cohort study of 5189 women who attended a fertility center in Hubei, China, during 2019-2022, and estimated concentrations of PM2.5 and its major constituents during the development of follicles (4th-6th month [W1], 0-4th month [W2], 0-6th month [W3]) and 1-year before measurement (W4) based on Tracking Air Pollution in China database. We used multivariable linear regression and logistic regression models to examine the associations of PM2.5 and its constituent exposures with anti-Müllerian hormone (AMH), the preferred indicator of ovarian reserve. RESULTS: We observed significantly decreased AMH levels associated with increasing PM2.5 concentrations, with the percent changes (95 % confidence intervals [CIs]) of 1.99 % (0.24 %-3.71 %) during W1 and 3.99 % (0.74 %-7.15 %) during W4 for per 10 µg/m3 increases in PM2.5.When PM2.5 exposure levels were equal to 50th percentile (32.6-42.3 µg/m3) or more, monotonically decreased AMH levels and increased risks of low AMH were seen with increasing PM2.5 concentrations during W1 and W4 (P < 0.05). Black carbon (BC), ammonium (NH4+), nitrate (NO3-), and organic matter (OM) during W1, and NH4+, NO3-, as well as sulfate (SO42-) during W4 were significantly associated with decreased AMH. Moreover, PM2.5 and SO42- exposures during W4 were positively associated with low AMH. Additionally, the associations were stronger among women aged <35 years, lived in urban regions, or measured AMH in cold-season (P for interaction <0.05). CONCLUSION: PM2.5 and specific chemical components (particularly NH4+, NO3-, and SO42-) exposure during the secondary to antral follicle stage and 1-year before measurement were associated with diminished ovarian reserve (DOR), indicating the adverse impact of PM2.5 and its constituent exposures on female reproductive potential.

The role of kurtosis and kurtosis-adjusted energy metric in occupational noise-induced hearing loss among metal manufacturing workers.

Background: Noise energy has been well-established to increase the risk of occupational noise-induced hearing loss (NIHL). However, the role of noise temporal structure (expressed by kurtosis) or its combination with energy metrics (e.g., kurtosis-adjusted cumulative noise exposure, adj-CNE) in occupational NIHL was still unclear. Methods: A cross-sectional survey of 867 Chinese workers, including 678 metal manufacturing workers and 189 workers exposed to Gaussian noise, was conducted. Noise energy metrics, including LAeq,8h and CNE, kurtosis (ß), and adj-CNE were used to quantify noise exposure levels. Noise-induced permanent threshold shift at frequencies 3, 4, and 6 kHz (NIPTS346) and the prevalence of high-frequency NIHL (HFNIHL%) were calculated for each participant. The dose-response relationship between kurtosis or adj-CNE and occupational NIHL was observed. Results: Among 867 workers, different types of work had specific and independent noise energy and kurtosis values (p > 0.05). HFNIHL% increased with an increase in exposure duration (ED), LAeq,8h, CNE, or kurtosis (p < 0.01), and there were strong linear relationships between HFNIHL% and ED (coefficient of determination [R2] = 0.963), CNE (R2 = 0.976), or kurtosis (R2 = 0.938, when CNE < 100 dB(A)∙year). The "V" shape notching extent in NIPTS became deeper with increasing kurtosis when CNE < 100 dB(A)∙year and reached the notching bottom at the frequency of 4 or 6 kHz. The workers exposed to complex noise (ß ≥ 10) had a higher risk of NIHL than those exposed to Gaussian noise (ß < 10) at the frequencies of 3, 4, 6, and 8 kHz (OR > 2, p < 0.01). Moreover, HFNIHL% increased with adj-CNE (p < 0.001). There were strong linear relationships between NIHL and adj-CNE or CNE when ß ≥ 10 (R2adj-CNE > R2CNE). After CNE was adjusted by kurtosis, average differences in NIPTS346 or HFNIHL% between the complex and Gaussian noise group were significantly reduced (p < 0.05). Conclusion: Kurtosis was a key factor influencing occupational NIHL among metal manufacturing workers, and its combination with energy metrics could assess the risk of NIHL more effectively than CNE alone.

Texture Feature Extraction from 1H NMR Spectra for the Geographical Origin Traceability of Chinese Yam.

Adulteration is widespread in the herbal and food industry and seriously restricts traditional Chinese medicine development. Accurate identification of geo-authentic herbs ensures drug safety and effectiveness. In this study, 1H NMR combined intelligent "rotation-invariant uniform local binary pattern" identification was implemented for the geographical origin confirmation of geo-authentic Chinese yam (grown in Jiaozuo, Henan province) from Chinese yams grown in other locations. Our results showed that the texture feature of 1H NMR image extracted with rotation-invariant uniform local binary pattern for identification is far superior compared to the original NMR data. Furthermore, data preprocessing is necessary. Moreover, the model combining a feature extraction algorithm and support vector machine (SVM) classifier demonstrated good robustness. This approach is advantageous, as it is accurate, rapid, simple, and inexpensive. It is also suitable for the geographical origin traceability of other geographical indication agricultural products.

Non-Isothermal Crystallization Kinetics of Montmorillonite/Polyamide 610 Nanocomposites.

Non-isothermal crystallization kinetics of montmorillonite (MMT)/polyamide 610 (PA610) composites were readily prepared by in situ melt polymerization followed by a full investigation in terms of their microstructure, performance, and crystallization kinetics. The kinetic models of Jeziorny, Ozawa, and Mo were used in turn to fit the experimental data, in all of which Mo's analytical method was found to be the best model for the kinetic data. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) studies were used to investigate the isothermal crystallization behavior and MMT dispersion levels in the MMT/PA610 composites. The experiment results revealed that low MMT content can promote the PA610 crystallization, whilst high MMT content result in MMT agglomeration, and reduce the PA610 crystallization rate.

Antineutrophil cytoplasmic antibody­associated vasculitis complicated with oral and maxillofacial space infection in a young woman: A case report.

Antibody-associated vasculitis (AAV) is a systemic autoimmune disease, with hormones and immunosuppressants as its main treatment measures. However, during the treatment process, various infections such as lung infections and urinary tract infections are prone to occur, and patients with OMSI are relatively rare. The present case report describes the case of a young woman who received long-term oral glucocorticoids and immunosuppressive agents for the treatment of antineutrophil cytoplasmic (AAV). At hospital admission, the patient with a high fever and painful swelling of the left side of the mouth. The patient was diagnosed with an oral and maxillofacial space infection (OMSI). Therefore, the local incision, drainage and irrigation of abscesses were subsequently performed. Additionally, the immunosuppressive agents were discontinued, the glucocorticoid dose was reduced and intravenous antibiotic therapy was provided. The patient was discharged 1 week later in good condition. Notably, the incidence of AAV is extremely low. Although OMSI is not uncommon, the simultaneous occurrence of AAV in combination with OMSI has not been reported previously. To the best of our knowledge, this is the first reported case of AAV combined with OMSI.

[Soil Heavy Metal Content, Pollution, and Influencing Factors in Typical Farming Area of Sichuan Basin].

In order to identify heavy metal contents, the pollution characteristics and influencing factors of soil in typical farming areas in the Sichuan basin were analyzed, with Jiangjin District of Chongqing City chosen as the study area. Two hundred and forty-seven topsoil samples were collected and analyzed using the Nemerow index (NPI), geographical information system (GIS), and geodetector method. The results demonstrated that: 1 the arithmetic means of Cd, Cu, and Zn in the topsoil were 1.22, 1.10, and 1.98 times that of the soil background values in western Chongqing, respectively. 2 The high-value areas of the six heavy metals were mainly distributed in the northern, western, and central Jiangjin district, whereas the low-value areas were distributed in the eastern and southern Jiangjin district. 3 The NPI showed that the polluted sample points accounted for 22.1% of the total sample points, indicating that the overall soil pollution was mainly safety and vigilance in general. The high value of NPI was distributed in Dingshan street in the northern Jiangjin district. 4 The explanatory power of stratum on the distribution of heavy metal contents in the topsoil was the strongest, followed by that of the topographic factor. The interaction effect of the stratum and topographic factors on the distribution of heavy metal content in soil was the strongest. The results showed that the stratum and topographic factors were the key factors affecting the distribution of soil heavy metal contents in the study area.

Effectiveness of Kurtosis-Adjusted Cumulative Noise Exposure in Assessing Occupational Hearing Loss Associated With Complex Noise.

OBJECTIVES: Occupational noise-induced hearing loss (NIHL) is one of the most prevalent occupational diseases worldwide. Few studies have been reported on applying kurtosis-adjusted noise energy (e.g., kurtosis-adjusted cumulative noise exposure, CNE-K) as a joint indicator for assessing NIHL. This study aimed to analyze the effectiveness of CNE-K in assessing occupational hearing loss associated with complex noise in typical manufacturing industries. DESIGN: A cross-sectional survey of 1404 Chinese manufacturing workers from typical manufacturing industries was conducted. General demographic characteristics, noise exposure data, and noise-induced permanent threshold shifts (NIPTS) at 3, 4, and 6 kHz (NIPTS 346 ) were collected and analyzed. The role of kurtosis in high-frequency noise-induced hearing loss (HFNIHL) was also analyzed. The degree of overlap of the two logistic curves (i.e., between complex noise CNE-K and HFNIHL%, and between Gaussian noise CNE and HFNIHL%) was used to evaluate the effectiveness of CNE-K, using a stratified analysis based on age, sex, industry, or job type. RESULTS: The binary logistic regression analysis showed that in addition to age, sex, exposure duration, and Eight-hour Continuous Equivalent A-weighted Sound Pressure Level (L Aeq,8h ), kurtosis was a key factor influencing HFNIHL% in workers (odds ratio = 1.18, p < 0.05), and its odds ratio increased with an increase in kurtosis value. Multiple linear regression analysis demonstrated that the contribution of kurtosis to NIPTS 346 was second to L Aeq,8h . Complex noise led to a higher risk of NIHL than Gaussian noise at frequencies of 3, 4, 6, and 8 kHz after adjusting for age, sex, and CNE ( p < 0.05). As kurtosis increased, the notch in the audiogram became deeper, and the frequency at which the notch began to deepen shifted from 3 to 1 kHz. The logistic curve between complex noise CNE-K and HFNIHL% nearly overlapped with that between Gaussian noise CNE and HFNIHL%, and the average difference in HFNIHL% between the two curves decreased from 8.1 to 0.4%. Moreover, the decrease of average difference in HFNIHL% between the two logistic curves was evident in several subgroups, such as male workers, aged <30 and 30 to 50 years, furniture and woodworking industries and gunning and nailing job types with relatively high kurtosis values. CONCLUSIONS: Kurtosis, as an indirect metric of noise temporal structure, was an important risk factor for occupational NIHL. Kurtosis-adjusted CNE metric could be more effective than CNE alone in assessing occupational hearing loss risk associated with complex noise.

Alcohol as a risk factor for hearing loss: A systematic review and meta-analysis.

OBJECTIVE: Growing evidence suggests that alcohol consumption is a risk factor for hearing loss; however, the evidence has been inconsistent. This systematic review and meta-analysis aimed to evaluate the effect of alcohol consumption on hearing loss. METHODS: We searched several databases up to November 2021, for published articles using the keywords "alcohol drinking" and "hearing loss". Two investigators independently conducted the study selection and data extraction. Based on the results of the heterogeneity analysis (Q statistic and I2 statistic), a fixed- or random-effects model was used to calculate the pooled odds ratios (ORs). Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and robustness of the pooled estimation. Publication bias in the literature was evaluated using Egger's test. RESULTS: In total, 18 (9 cross-sectional, 5 case-control, and 4 cohort) observational studies were identified in this search; 27,849 participants were included. Compared with non-drinkers, the pooled OR of drinkers was 1.22 (95% confidence interval: 1.09-1.35). CONCLUSION: Evidence suggests a positive association between alcohol consumption and hearing loss. Drinkers were at a higher risk than non-drinkers. Drinking limitations may be useful for preventing hearing loss.

In vitro antifungal activity of Shikonin against Candida albicans by inducing cellular apoptosis and necrosis.

BACKGROUND: Our previous studies showed that Shikonin (SK) had a strong anti-Candida albican (C. albicans) activity, especially against some fluconazole-resistant strains, which is probably due to the oxidative damage of SK to C. albicans. METHODS AND RESULTS: In this study, we expanded the antifungal spectrum and evaluate the toxicity of SK. The results indicated that SK also exhibited potent invitro antifungal activities against other pathogenic fungi such as other Candida, Aspergillus, Cryptococcus, and Dermatophytes, but did not display apparent toxicity to the mammalian cells, suggesting that SK is safe to be a potential antifungal drug. Furtherly, we analyze the exact mechanism of SK against C. albicans. We found that SK could induce a series of apoptosis characteristics, including phosphatidylserine externalization, chromatin condensation and fragmentation, decreased cytochrome c oxidase activity as well as caspase activation. CONCLUSIONS: In summary, this study highlighted the antifungal activity and mechanism of SK against C. albicans, providing a potential therapeutic strategy for C. albicans infection.

Quantitative 1H NMR with global spectral deconvolution approach for the determination of gamma-aminobutyric acid in Chinese yam (Dioscorea polystachya Turczaninow).

We developed a quantitative proton nuclear magnetic resonance (qNMR) with global spectral deconvolution (GSD) method to determine the gamma-aminobutyric acid content in Chinese yam with the proton signal at δH 2.30. Trimethylsilyl-2,2,3,3-tetradeuteropropionic acid sodium salt was set as the internal standard. The method was validated and showed admissible stability, repeatability, and precision. Compared to the traditional high-performance liquid chromatography method, this method did not involve tedious pre-treatment and expensive standard. Compared to ordinary qNMR, GSD algorithm could effectively remove the effect of noise, baseline distortions and signal overlapping. Overall, qNMR with GSD method is a rapid, simple and reliable method to quantitatively determine functional metabolites even overlapped with other compounds in herbs or foods.

Associations of physical activity intensity with incident cardiovascular diseases and mortality among 366,566 UK adults.

BACKGROUND: The associations of the proportion of vigorous physical activity (VPA) to moderate to vigorous physical activity (MVPA) with incident cardiovascular disease (CVD) and all-cause mortality are unclear. METHODS: The present study included 366,566 participants (aged 40-69 years) without baseline CVD from the UK biobank during 2006 to 2010. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of outcomes. RESULTS: During a median 11.8 years of follow-up, among 366,566 participants (mean age [SD]: 56.0 [8.1]), 31,894 incident CVD and 19,823 total deaths were documented. Compared with no VPA, 0%-30% of VPA to MVPA was associated with 12% and 19% lower risks of incident CVD (HR, 0.88 [95% CI, 0.86-0.91]) and all-cause mortality (HR, 0.81 [95% CI, 0.78-0.84]), respectively. Furthermore, we found that the maximum reduction of risks of incident CVD and all-cause mortality occurred at performing approximately 30% of VPA to MVPA (P < 0.001). Compared with participants reporting the lowest levels of MVPA (moderate physical activity [MPA], 0-150 min/week; VPA, 0-75 min/week), those performing 150-300 min/week of MPA and ≥ 150 min/week of VPA experienced the lowest risk of incident CVD (HR, 0.87 [95% CI, 0.79-0.95]) and all-cause mortality (HR, 0.71 [95% CI, 0.63-0.80]). Interestingly, we found that smokers yielded more cardiovascular benefits than non-smokers by performing a higher volume of VPA. CONCLUSIONS: Comparing with UK adults reporting no VPA, engaging in 30% of VPA was associated with the lowest risk of incident CVD and all-cause mortality.

Frailty and hearing loss: From association to causation.

Background: Observational studies suggest that frailty is associated with hearing loss (HL) but with inconsistent results. This study aims to examine such association and to assess its causality. Materials and methods: The cross-sectional data from the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression models were used to assess the association between HL and frailty index (FI). Genetic variants associated with the FI and HL were obtained from a large genome-wide association study (GWAS) meta-analysis and UK Biobank GWAS. The inverse variance weighting (IVW) method was used to estimate causal effects. Sensitivity analyses were performed to further validate the robustness of results. Results: In this cross-sectional analysis, results support the possibility that frailty may be associated with a higher risk of developing HL, with self-reported [odds ratio (OR) = 2.813; 95% CI, 2.386, 3.317; p < 0.001], speech frequency HL (OR = 1.975; 95% CI, 1.679-2.323; p < 0.001), and high frequency HL (OR = 1.748; 95% CI, 1.459-2.094; p < 0.001). In the adjusted model, frail participants remained at high risk of HL. Mendelian randomization (MR) studies showed a bidirectional causal association between genetically predicted FI and risk of HL (FI for exposure: OR = 1.051; 95% CI, 1.020-1.083; p = 0.001; HL for exposure: OR = 1.527; 95% CI, 1.227-1.901; p < 0.001). Conclusion: Our observational study found that inter-individual differences in frailty were associated with the risk of developing HL. Genetic evidence suggests a potential bidirectional causal association between FI and HL. Furthermore, the potential mechanisms of this association require investigation.

Telomere Length and Hearing Loss: A Two-Sample Mendelian Randomization.

BACKGROUND: Observational studies have suggested that there may be an association between telomere length (TL) and hearing loss (HL). However, inferring causality from observational studies is subject to residual confounding effects, reverse causation, and bias. This study adopted a two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between TL and increased risk of HL. METHODS: A total of 16 single nucleotide polymorphisms (SNPs) associated with TL were identified from a genome-wide association study (GWAS) meta-analysis of 78,592 European participants and applied to our modeling as instrumental variables. Summary-level data for hearing loss (HL), age-related hearing loss (ARHL), and noise-induced hearing loss (NIHL) were obtained from the recent largest available GWAS and five MR analyses were used to investigate the potential causal association of genetically predicted TL with increased risk for HL, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode. In addition, sensitivity analysis, pleiotropy, and heterogeneity tests were also used to evaluate the robustness of our findings. RESULTS: There was no causal association between genetically predicted TL and HL or its subtypes (by the IVW method, HL: odds ratio (OR) = 1.216, p = 0.382; ARHL: OR = 0.934, p = 0.928; NIHL: OR = 1.003, p = 0.776). Although heterogenous sites rs2736176, rs3219104, rs8105767, and rs2302588 were excluded for NIHL, the second MR analysis was consistent with the first analysis (OR = 1.003, p = 0.572). CONCLUSION: There was no clear causal relationship between shorter TLs and increased risk of HL or its subtypes in this dataset.