Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.

Background Temporal kurtosis (without frequency weighting, i.e., Z-weighted kurtosis) can evaluate noise-induced hearing loss (NIHL). However, few studies have considered the function of frequency weighting (A- or C-weighted) kurtosis on NIHL. Objective To study the significance of A- and C-weighted kurtosis adjustment for equivalent sound level (L'_{EX,8 h}) in evaluating occupational hearing loss. Methods A cross-sectional survey was used to select 973 noise-exposed workers in seven industries as the subjects. The noise exposure of all workers was assessed by distributions of A-, C-, and Z-weighted kurtosis (e.g., K_A, K_C, and K_Z) and respective adjusted equivalent sound level (e.g., L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z). The significance of A- and C-weighted kurtosis in evaluating NIHL was evaluated by correlations between three types of L'_{EX,8 h} and NIHL, and improvement of noise-induced permanent threshold shift (NIPTS) underestimation predicted by the ISO prediction model (Acoustics—Estimation of noise-induced hearing loss, ISO 1999-2013). Results The median K_A, K_C, and K_Z were 68.33, 28.22, and 19.82, respectively. The binary logistic regression showed that L_{EX, 8 h}-K_A, L_{EX, 8 h}-K_C, and L'_{EX, 8 h}-K_Z were risk factors for NIHL (OR>1, P<0.001). The receiver operating characteristic (ROC) curve showed that when the outcome variable was noise-induced hearing impairment (NIHI), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.625, 0.628, and 0.625, respectively. When the outcome variable was high-frequency noise-induced hearing loss (HFNIHL), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX, 8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.624, 0.623, and 0.622, respectively (P<0.05). The order of underestimation improvement values predicted by L'_{EX,8 h} for NIPTS₁₂₃₄ was: L'_{EX,8 h}-K_A (4.68 dB HL)>L'_{EX,8 h}-K_C (4.38 dB HL)>L'_{EX,8 h}-K_Z (4.28 dB HL) (P<0.001). The order of underestimation improvement values predicted by L'_{EX,8 h}-K for NIPTS₃₄₆ was: L'_{EX,8 h}-K_A (7.20 dB HL)>L'_{EX,8 h}-K_C (6.83 dB HL)>L'_{EX,8 h}-K_Z (6.71 dB HL) (P<0.001). Conclusion The adjustment of A- and C-weighted kurtosis to equivalent sound level L_{EX,8 h} can effectively improve the accuracy of the ISO 1999 prediction model in NIPTS prediction, and compared with the C-weighted, the A-weighted kurtosis can improve the result of the ISO 1999 prediction model in terms of underestimating NIPTS.

background Current assessment of noise-induced hearing loss relies on the hearing threshold statistical distribution table of ISO 7029-2017 standard (ISO 7029), which is based on foreign population data and lacks a hearing threshold distribution table derived from pure-tone audiometry data of the Chinese population, hindering accurate evaluation of hearing loss in this group. Objective To establish a statistical distribution table of hearing threshold level (HTL) for otologically normal Chinese adults and to provide a scientific basis for revising the diagnostic criteria of occupational noise-induced deafness in China. Methods A total of 1271 otologically normal Chinese adults aged 18-60 years were divided into four groups with 10-year age intervals. Based on the pure tone audiometry data and power function operation formula, the relevant parameters of the median and percentile calculation formula of ISO 7029 were adjusted. Based on the adjusted parameters, a statistical distribution table of HTL of normal Chinese adults in otology was preliminarily constructed according to the calculation formula of ISO 7029. A nonparametric rank sum test was used to compare the difference between the adjusted median deviation value and the ISO 7029 calculation. Results Except for a few frequencies (2000, 3000, and 8000 Hz), the value of parameter α adjusted for the auditory threshold deviation of the Chinese population (α_CHN-md) increased with the increase of frequency, while the value of parameter β adjusted for the auditory threshold deviation of the Chinese population (β_CHN-md) decreased with the increase of frequency. The preliminary distribution table of otologically normal Chinese adults' median hearing threshold deviation (ΔH_CHN-md) showed that the hearing threshold deviation increased with age and frequency. At 8000 Hz, the increase in ΔH_CHN-md with age was the greatest for both men and women, from 0 dB to 23 dB and 21 dB respectively. The minimal threshold elevation was noted at 500, 1000, and 2000 Hz, which increased from 0 dB to 2 dB. In otologically normal Chinese adults, the maximum increase of ΔH_CHN-md with frequency was observed at age of 50 years, which increased from 2 dB at 500 Hz to 23 dB at 8000 Hz in men and from 2 dB at 500 Hz to 21 dB at 8000 Hz in women. The comparison results with the ISO 7029 calculation showed that the trend was consistent. The median hearing threshold deviation value of the adjusted Chinese population was lower than that of the ISO 7029 calculation (ΔH_md). However, they had no significant statistical difference (P>0.05). For otologically normal normal Chinese men and women, the maximum difference of ΔH_md between the 50-year-old group and the ISO calculation at 8000 Hz was 7 dB and 9 dB, respectively. Conclusion This preliminary analysis of hearing threshold deviations in otologically normal Chinese adults suggests that current standards may potentially underestimate hearing loss at frequencies below 8000 Hz while possibly overestimating it at 8000 Hz. These findings require further validation through expanded sample sizes to more accurately assess the characteristics of hearing thresholds in the Chinese population and their discrepancies with existing standards.

Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

Objective To evaluate the noise hazard level of a coal mining enterprise, and identify high-risk operation types and people, and to provide a basis for preventing and controlling the health damage caused by noise. Methods A large coal mining enterprise in Shaanxi Province was selected as the research object. The noise monitoring data of the coal mine over the years was used to calculate the noise exposure matrix of each post in the enterprise, and the classification of occupational hazards at workplaces (GBZ/T 229.4-2012) was used to assess the occupational health risk levels. Results Among the 22 noise-exposed positions in the enterprise, the 8-hour working day equivalent sound level in positions of shearer driver, horseshoe driver, crusher driver, shuttle driver, relaxation screen driver, and grading screen driver were all higher than the occupational exposure limit of noise. In 2021, the noise exposure levels of shearer drivers, crusher drivers, and coal-selecting workers were all higher than 90 dB (A), and the occupational hazard level was moderate hazard level. In addition, the noise exposure levels of most other jobs also exceeded the occupational exposure limit. Conclusion The noise hazards in the coal mine industry are mainly concentrated in the posts of the coal mining system, tunneling system, and screening workshop. Among them, the shearer driver, the crusher driver, and the coal preparation workers have higher noise exposure levels. It is recommended to take corresponding noise reduction measures and strengthen the protection level to reduce the noise exposure risk of workers.

Background Job burnout has become an important factor affecting the mental and physical health and work efficiency of college counselors, and indirectly affects the quality and development of talent cultivation for college students. Objective To explore the relationship between job stress, job crafting, and job burnout among college counselors, and to test the mediating role of job crafting between job stress and job burnout, in order to take targeted measures to alleviate job stress and job burnout of college counselors, reduce associated health risks, and improve the effectiveness of higher education. Methods An anonymous questionnaire survey was conducted among 400 counselors from social network communication groups by convenience sampling. The Counselor Work Stress Scale, Job Crafting Scale, and Maslach Burnout Inventory-General Survey were used. Harman's single-factor method was used to evaluate common method bias in the survey data. One-way ANOVA was applied to test the difference in job stress, job crafting, and job burnout among college counselors by demographic characteristics, and chi-square test was used to analyze the difference in reporting job burnout. Partial correlation analysis was used to evaluate the correlation between selected variables. Structural equation modeling was used to analyze the relationship of job stress, job crafting, and job burnout among college counselors, and Bootstrap analysis was used to test if there was a mediating effect of job crafting on the relationship between job stress and job burnout. Results Of the 390 questionnaires recovered, there were 338 valid questionnaires (86.67%). Among the included subjects, the mean scores of job stress, job crafting, and job burnout were (2.70±0.62), (3.77±0.62), and (2.09±1.09), respectively. The positive rate of job burnout was 76.9% (260/338), with a positive rate of 72.8% in exhaustion dimension and 59.8% in cynicism dimension. There were significant differences in job crafting scores among the college counselors by different genders and professional titles (P<0.05). Female counselors had significantly higher job burnout scores and positive rates than male counselors (P<0.05). The partial correlation analysis showed that job stress, work load, school evaluation and expectation, and interpersonal relationship were positively correlated with job burnout (r=0.562, 0.442, 0.473, and 0.455, respectively, P<0.01), and negatively correlated with job crafting (r=−0.271, −0.169, −0.246, and −0.247, respectively, P<0.01); job crafting, cognitive crafting, relationship crafting, and task crafting were negatively correlated with job burnout (r=−0.447, −0.452, −0.366, and −0.340, respectively, P<0.01). The modified structural equation modeling indicated that job stress negatively affected job crafting (b=−0.348, P<0.001) and positively affected job burnout (b=0.454, P<0.001); job crafting negatively affected job burnout (b=−0.459, P<0.001), and played a partial mediating role in the relationship between job stress and job burnout, and the effect value was 0.160 (95%CI: 0.102, 0.230) that accounted for 26.10% of the total effect. Conclusion Job burnout among the college counselors is prominent. Job crafting presents an inhibitory effect on job burnout. Job stress indirectly affects the occurrence of job burnout by inhibiting the generation of job crafting.

Objective To compare the effect of rubber ring versus dental floss combined with hemoclipping assisted en-doscopic submucosal dissection(ESD)in the treatment of early gastrointestinal tumor.Methods A total of 103 patients with early gastrointestinal cancer were divided into the rubber band traction group(rubber band group,n=51)and the dental floss traction assist group(dental floss group,n=52)according to different assisted traction techniques during ESD.The basic con-ditions of the two groups were compared before operation,as well as the amount of submucosal injection,installation time of the traction device,the amount of bleeding during operation,the time of operation,the delayed bleeding after operation,one-time complete resection rate of tumor,days in hospital after operation and complication rate at 72 hours after operation.The degree of postoperative pain(VAS pain Score),follow-up quality of life(SF-36 Score)and complications 12 months after op-eration were also recorded.Results The intraoperative submucosal injection volume,intraoperative bleeding volume,num-ber of hemostatic clamp detachment,surgical time,complication rate 72 hour after operation and postoperative hospital stay were lower in the rubber band group than those in the dental floss group(P＜0.05).There was no significant difference in the number of delayed postoperative bleeding between the two groups(P＞0.05).After 12 months of follow-up,patients in the rubber band group had mild postoperative pain and good quality of life.The incidence of complications decreased within 12 months after surgery in the rubber band group(P＜0.05).Conclusion Compared with floss traction aid,rubber ring traction aid ESD can shorten the operation time and reduce postoperative complications,which is worth popularizing.