Background Non-optimal temperatures pose significant threats to public health. Analyzing the association between temperature exposure and the number of emergency cases of acute alcohol intoxication can provide evidence for optimizing emergency resource allocation and response strategies. Objective To analyze the overall impact and lag effects of non-optimal temperatures on the number of 120 emergency calls for acute alcohol intoxication in Wuxi, and to assess the attributable risk, in order to provide empirical evidence for formulating climate-adaptive public health strategies. Methods Call records of acute alcohol intoxication from Wuxi's 120 emergency service, concurrent air pollutant data, and meteorological data (including daily mean temperature) were collected from January 1, 2014 to December 31, 2020. Distributed lag nonlinear modeling was used for time-series analysis, with cross-basis functions to capture the nonlinear relationship and lag effects between temperature and emergency volume. Confounding factors such as long-term trends, humidity, pollutants [ultimately including ozone (O₃) and fine particulate matter (PM_2.5)], day of the week, and holidays were controlled. The maximum lag period was set to 14 days. Single-day lag and cumulative lag effects of extreme temperatures were analyzed, followed by sensitivity analysis. Effects were quantified using relative risk (RR) and 95% confidence intervals (95%CI), and attributable fractions and numbers for different temperature ranges were calculated. Results A total of 10705 emergency cases of acute alcohol intoxication were included during the study period, with males accounting for 89.5% and individuals aged 18–50 years accounting for 83.4%. A non-linear "U-shaped" association was observed between daily mean temperature and the number of emergency calls, with an optimal temperature of 13.3 ℃. The effect of the extreme low temperature (1.88 ℃) was statistically significant from lag1 to lag3 after exposure (P<0.05), with the maximum effect at lag1 (RR=1.063, 95%CI: 1.002, 1.129). The extreme high temperature (32.3 ℃) showed an immediate effect, with maximum effect at lag0 (RR=1.374, 95%CI: 1.248, 1.512). The cumulative effect analysis showed that the risk associated with high temperature was the highest at lag0–3 (RR=2.000, 95%CI: 1.667, 2.399), while the risk associated with low temperature was the highest at lag0–14 (RR=1.462, 95%CI: 1.042, 2.051). The attribution analysis indicated that the mild heat (>24.7–30.8 ℃) and heat (>30.8–33.5 ℃) contributed the largest numbers of attributable cases, with 591 cases (95%CI: 56, 1032) and 190 cases (95%CI: 51, 309), respectively. The corresponding attributable fractions were 5.81% (95%CI: 0.80%, 9.94%) and 1.87% (95%CI: 0.49%, 2.96%), respectively. Conclusion Both extreme high and low temperatures significantly increase the number of 120 emergency calls for acute alcohol intoxication in Wuxi. High temperature exhibit an acute effect, while low temperature show a delayed effect. Mild heat have a significant impact on the emergency burden. It is recommended that emergency departments optimize resource allocation according to climatic characteristics and strengthen emergency responses during extreme weather to reduce alcohol-related health burden.

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

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

Background Tributyl phosphate (TBP) is widely used as an organophosphate flame retardant. However, there are limited studies on the toxicity of TBP to aquatic organisms at low levels of exposure. Objective To investigate the effects of TBP on early development of zebrafish (Danio rerio). Methods Zebrafish embryos were randomly divided into four groups at 2 h post-fertilisation (2 hpf), namely, the 0.01% dimethyl sulfoxide (DMSO) control group and TBP exposure groups (0.02, 0.2 and 2 μg·L⁻¹). The exposure time was from 2 hpf to 120 hpf and the hatching rate, malformation rate, heart rate and body length of zebrafish embryos at 72 hpf, the frequency of tail curling at 24-29 hpf, the locomotor ability at 96 hpf and the survival rate at 120 hpf were evaluated, respectively. The whole-body triiodothyronine (T₃) and tetraiodothyronine (T₄) levels of juvenile fish were measured by enzyme immunoassay at the end of the infection, and the expression levels of hypothalamic-pituitary-thyroid axis (HPT) and neurodevelopmental-related genes were detected by quantitative real-time PCR (q-PCR). Results The heart rates of zebrafish embryos were significantly decreased in all TBP-treated groups (P<0.001), the survival rates of the 0.02 and 2 μg·L⁻¹ TBP groups were significantly decreased (P<0.05), and the malformation rate of the 2 μg·L⁻¹ treated group was significantly increased (P<0.05), which was mainly manifested by pericardial oedema. The frequency of tail curling of zebrafish embryos in all groups reached the highest at 25 hpf, which was significantly lower (P<0.001) in all exposure groups than in the control group (P<0.001). In the locomotor behaviour experiments, the swimming speed of zebrafish larvae in the dark cycle was significantly decreased in the 0.02 and 0.2 μg·L⁻¹ TBP groups (P<0.05), and similar results were found for the light cycle in the 0.2 and 2 μg·L⁻¹ TBP groups (P<0.05). Compared with the control group, the T₃ level of zebrafish juveniles in the 0.2 μg·L⁻¹ TBP group increased significantly (P<0.05). The q-PCR results showed that the expression levels of HTP axis-related genes [thyroid hormone receptors (trα, \begin{document}$tr\beta $\end{document}), thyroglobulin (tg), and sodium/iodide co-transporter (nis)] were significantly down-regulated in the exposure groups, the expression level of transthyretin (ttr) was significantly up-regulated in the 0.02 μg·L⁻¹ TBP group, and the iodothyronine deiodinase 2 (dio2) expression level was significantly down-regulated in the 0.02 μg·L⁻¹ TBP group (P<0.05); the neurodevelopment-related gene acetylcholinesterase (ache) was significantly down-regulated in the exposure groups, and the expression levels of myelin basic protein (mbp) and Elav like neuron-specific RNA binding protein 3 (elavl3) were significantly down-regulated in the 0.02 μg·L⁻¹ TBP group (P<0.05). Conclusion TBP exposure can lead to early developmental abnormalities in zebrafish, manifested as developmental toxicity, thyroid endocrine disruption and neurotoxicity during hatching and early juvenile stages.

End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-Ⅱ(MAL-Ⅱ)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein β8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

The protection effect of flash-radiotherapy(Flash-RT)with super-high dose on normal tissue has obtained wide attention in therapeutic radiology since it was found in 2014 year.The increasing research demand of Flash-RT with super-high dose-rate proposed new challenge for the existing radiotherapy equipment.Based on the demands of FLASH-RT research and clinical application,this review analyzed the proposed new requirement of Flash-RT for equipment,and introduce current scientific facilities with the experimental ability of X-ray FLASH-RT,as well as the situation of the specialized FLASH-RT equipment which were developing.The research of Flash-RT mechanism need the existing equipment with high-energy X-ray source develop toward high power,while the clinical application of Flash-RT demand these transient high-power devices should possess a series of radiotherapy techniques such as multi angle irradiation,conformal radiotherapy and others.Currently,China's X-ray FLASH-RT research is at the forefront of the world,which is expected to achieve the first breakthrough of high-end medical equipment in the X-ray Flash RT field.

Objective:To explore the relationship between the ultrasound parameters of reproductive system and the expression of endocrine hormone in female pediatric patients with precocious puberty(PP),and to assess the treatment effect.Methods:A total of 160 female pediatric patients with PP who admitted to Beijing Jingmei Group General Hospital from January 2021 to December 2021 were selected,and they were divided into a positive group and a normal group based on the diagnostic criteria for precocious puberty,with 80 cases in each group.Ultrasound examination was performed on the uterus,ovaries and breasts of 160 female pediatric patients with PP,and the relevant parameters of them were measured,and the levels of endocrine hormone in the serums of them were detected.The pediatric patients of positive group underwent again the ultrasound examination and the detection of endocrine hormone after they completed treatment.The differences of ultrasound parameters and endocrine hormone between two groups were compared,and the correlation of ultrasound parameters and endocrine hormone between two groups were analyzed,as well as the influence factors of treatment effect.Results:The length and thickness of the uterus,the ratio of the length of the uterus to the length of cervix,the thickness of the endometrium,the size of the ovaries,the number of follicles,and the width and thickness of the hypoechoic area of the breast in the positive group were significantly larger than them in the normal group,and the differences of them were statistical significance(t=16.8,12.6,12.4,14.7,11.5,15.8,10.9,10.2,P<0.05),respectively.The resistance index(RI)of uterine artery of positive group was significantly smaller than that of normal group,and the difference was statistically significant(t=-7.9,P<0.05).The serum estradiol(E2),gonadotropin(GnRH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),progesterone(P)and growth hormone(GH)levels of positive group were significantly higher than those of normal group,and the differences of them were significant(t=20.6,19.8,15.4,17.6,15.2,8.9,P<0.05),respectively.After treatment,the above-mentioned ultrasound parameters and endocrine hormone levels of the pediatric patients in the positive group were significantly improved.The relevant analysis showed that ultrasound parameters were positively correlated with levels of endocrine hormone,and they were important influence factor on the levels of endocrine hormone.In addition,the treatment effect was related to ultrasound parameters(OR=0.78-1.28,P<0.05),the levels of endocrine hormone(OR=0.73-0.77,P<0.05),age,height,weight and BMI(OR=0.70-0.72,P<0.05).Conclusion:The ultrasound parameters of the reproductive system of female pediatric patients with PP are closely related to the expression of endocrine hormones.The levels of endocrine hormones can be used as important indicators of the disease condition and prognosis of female pediatric patients with PP.