Background Co-exposure to noise and microwave radiation occurs frequently. The central nervous system has been identified as a sensitive target organ for both noise and microwave exposure individually, and the underlying mechanisms remain poorly understood. The specific biological effects resulting from co-exposure to these two factors have yet to be fully elucidated. Objective To clarify the effects of co-exposure to noise and microwave on neurobehavior and hippocampal tissue structure, and to explore the underlying mechanism through the assessment of serum cytokines. Methods C57BL/6N mice were selected and randomly assigned to a blank control group, a noise group, a microwave group, and a combined noise & microwave exposure group. To establish the exposure models, the noise group was subjected to broadband noise at 100 dB for 2 h, while the microwave group received radiation at a central frequency of 9.375 GHz with an average power density of 12 mW·cm⁻² and a specific absorption rate of 2.58 W·kg⁻¹ for 15 min. Open field and tail suspension tests assessed anxiety-like emotional behaviour; novel object recognition and Y-maze tests evaluated cognitive function. Histological changes in hippocampal tissue were examined using haematoxylin and eosin (HE) staining, and Nissl staining under light microscopy. Serum cytokine levels were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). Results After 3 d of exposure, the noise, microwave, and combined exposure groups showed significant reductions in exploration frequency, duration, and distance within the central zone of the open field test compared to the control group (P < 0.01); the combined exposure group exhibited increased ratios of peripheral-to-central exploration time and distance (P < 0.05). After 7 d of exposure, compared with the control group, the noise group maintained a decrease in central zone exploration time (P < 0.01), while the combined exposure group showed persistent decline across all central zone metrics (P < 0.05) and elevated peripheral-to-central ratios (P < 0.05); compared to the microwave group, the combined exposure group showed significant less time in the central zone (P < 0.05) and higher peripheral-to-central ratios (P < 0.05). Regarding behaviour and cognition, compared with the control group, the combined exposure group showed increased immobility time in the tail suspension test after 3 d of exposure (P < 0.01). At this interval, all exposure groups demonstrated reduced frequency and duration of novel object recognition (P < 0.05), with the combined exposure group showing a marked decrease in novel arm exploration time (P < 0.01). After 7 d of exposure, compared with the control group, the noise group showed reduced novel object recognition frequency (P < 0.05), and both the noise and microwave groups exhibited decreased novel arm exploration time (P < 0.05). Pathological alterations including an increased number of hyperchromatic nuclei and depleted Nissl bodies were observed in the CA3 and DG regions across all exposure groups with the most severe lesions observed in the combined exposure group. Serum levels of central nervous system-specific protein β (S-100β), glial fibrillary acidic protein (GFAP), and corticosterone (CORT) were significantly elevated in all exposure groups compared with the control group (P < 0.05). Aquaporin-4 (AQP4) levels increased in the combined exposure group (P < 0.05), while CXC chemokine ligand 10 (CXCL10) levels rose in both the noise and combined groups compared with the control group (P < 0.05). Specifically, S-100β and CXCL10 levels in the combined exposure group were higher than those in the microwave group (P < 0.05); moreover, levels of S-100β, GFAP, CORT, AQP4, and CXCL10 in the combined exposure group were significantly higher than those in the noise group (P < 0.05). Conclusion Combined exposure to noise and microwave radiation induces pathological changes in the hippocampus of mice, increases levels of serum stress hormones and neuro-specific biomarkers. These impairments are more severe than those observed following single-factor exposure. The underlaying mechanism may be related to systemic stress response, neuronal damage, astrocyte activation, and changes in blood-brain barrier permeability, leading to emotional behavioral abnormalities and cognitive decline.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Falls are one of the most common injuries, with a high prevalence and risk of disability, which poses the greatest threat to the health of the elderly. Falls are influenced by a variety of factors, including environmental factors such as slippery pavements, poor meteorological conditions, and inadequate lighting. The Sixth Assessment Report of the United Nations Intergovernmental Panel on Climate Change (IPCC) stated that climate change has become more frequent and stronger in recent years, which may threat people's health and lives. This review summarized the progress of epidemiological studies on the association between meteorological factors (e.g. temperature, precipitation, frost, and snowfall) and falls, and found that most of the studies focused on the association between temperature and falls, and the results of different studies varied greatly. While the studies on the association between other meteorological factors and falls were relatively few. Moreover, the mechanisms behind the associations were unclear. Therefore, we point out that it is necessary to further conduct large-sample and multi-centre studies to evaluate the effects of exposure to multiple meteorological factors, and further to explore the mechanisms of the associations, which may provide scientific evidence for better response to climate change.

Objective To investigate the correlation between the Balkwill angle and occlusal plane angles and temporomandibular joint(TMJ)morphology in adults with skeletal Class Ⅱ division 2 malocclusion.Methods Thirty-five adult patients with skeletal Class Ⅱ division 2 low angle(study group)and 35 adult patients with skeletal Class Ⅰ average angle(control group)were included.The Invivo Dental 5 software was employed to acquire the data of Balkwill angle,occlusal plane angle(FH-OP),posterior occlusal plane angle(FH-POP),mandibular occlusal plane angle(FH-MOP),DPO(vertical distance from condylar center to the MOP)and the TMJ measurement items.Results The mean values of FH-OP,FH-POP and FH-MOP were lower in the study group than control group(P＜0.05).The average value of Balkwill angle and DPO were higher in the study group than the control group(P＜0.05).Sig-nificant differences were found in the measurement results of the mediolateral diameters of the condyle,width of condylar head,the ar-ticular eminence inclination and height,superior joint space between two groups.DPO had a medium correlation with mediolateral di-ameters of the condyle,glenoid fossa depth and articular eminence height.And FH-MOP angle had a medium correlation with mediolat-eral diameters of the condyle and articular eminence height.There was a medium correlation between the Balkwill angle and articular eminence height,a weak correlation with mediolateral diameters of the condyle,articular eminence inclination,condylar length and glenoid fossa depth.Conclusion The results indicated that the DPO had a significant impact on TMJ morphology,followed by FH-MOP,and finally Balkwill angle in skeletal Class Ⅱ division 2 low angle malocclusion.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective To investigate the correlation between the Balkwill angle and occlusal plane angles and temporomandibular joint(TMJ)morphology in adults with skeletal Class Ⅱ division 2 malocclusion.Methods Thirty-five adult patients with skeletal Class Ⅱ division 2 low angle(study group)and 35 adult patients with skeletal Class Ⅰ average angle(control group)were included.The Invivo Dental 5 software was employed to acquire the data of Balkwill angle,occlusal plane angle(FH-OP),posterior occlusal plane angle(FH-POP),mandibular occlusal plane angle(FH-MOP),DPO(vertical distance from condylar center to the MOP)and the TMJ measurement items.Results The mean values of FH-OP,FH-POP and FH-MOP were lower in the study group than control group(P＜0.05).The average value of Balkwill angle and DPO were higher in the study group than the control group(P＜0.05).Sig-nificant differences were found in the measurement results of the mediolateral diameters of the condyle,width of condylar head,the ar-ticular eminence inclination and height,superior joint space between two groups.DPO had a medium correlation with mediolateral di-ameters of the condyle,glenoid fossa depth and articular eminence height.And FH-MOP angle had a medium correlation with mediolat-eral diameters of the condyle and articular eminence height.There was a medium correlation between the Balkwill angle and articular eminence height,a weak correlation with mediolateral diameters of the condyle,articular eminence inclination,condylar length and glenoid fossa depth.Conclusion The results indicated that the DPO had a significant impact on TMJ morphology,followed by FH-MOP,and finally Balkwill angle in skeletal Class Ⅱ division 2 low angle malocclusion.

Objective: To investigate the distribution of toxoplasma cysts in the brain of infected mice and the effect of pathological changes on the behavior and neuropsychiatry of the mice during chronic infection with Toxoplasma gondii( T．gondii) ． Methods : Mice were infected with Prugniaud strain of T．gondii by oral gavage．The brain tissues of infected mice were collected on the days of 10，30，40，90，120 and 160 after infection respectively，and the hippocampal hypothalamus，prefrontal lobe ，striatum and cerebellum regions were separated．The number of cysts and neuropathological changes in each infected area were observed and recorded by HE staining．The number of cysts and neuropathological changes in each infected area were observed and recorded. Results : T．gondii infected mice showed symptoms of vertical hair and arched back，which were the most significant on the 40th day，and then gradually recovered with hemiplegia and circling in circles． At each time point ，the number of toxoplasma cysts was the largest in hippocampal hypothalamus，followed by prefrontal lobe and striatum，and the least in cerebellum．The diameter of toxoplasma cysts increased with time．During chronic infection，specific pathological manifestations of toxoplasma encephalitis，such as neuronophagy，were observed in all regions of the brain tissue．The above pathological changes of toxoplasma encephalitis reached the peak on the 40th day，and gradually recovered， and increased to the stimulation peak on the 120th day，and then gradually recovered． Conclusion The behavioral and neuropsychiatric symptoms of T．gondii during chronic infection were correlated with the localization and distribution of toxoplasma cysts in the brain of infected mice，and showed dynamic changes.

Background: and Purpose By measuring a newly defined parameter, the carotid–cerebral pulse wave velocity (ccPWV), this study aimed to determine the association of intracranial artery calcification (IAC) with arterial stiffness as reflected by the pulse wave velocity between the carotid and middle cerebral arteries using transcranial Doppler sonography in patients with acute stroke. Methods: We recruited 146 patients with ischemic stroke from our stroke center. Computed tomography of the head was used to assess the presence and severity of IAC. Arterial stiffness was evaluated using ccPWV. Data are presented as quartiles of ccPWV. A multivariable logistic regression model was used to assess the independent relationship between ccPWV and IAC. Results: The IAC prevalence increased with the ccPWV quartile, being 54%, 76%, 83%, and 89% for quartiles 1, 2, 3, and 4, respectively (p<0.001) as did IAC scores, with median [interquartile range] values of 0 [0–2], 3 [2–4], 4 [2–5], and 5 [4–6], respectively (p<0.001). After additionally adjusting for age and hypertension, a significant correlation was only found between quartiles 3 and 4 of ccPWV and IAC scores. The odds ratio (95% confidence interval) for the IAC scores was 1.78 (1.28–2.50) (p=0.001) in quartile 4 of ccPWV and 1.45 (1.07–1.95) (p=0.015) in quartile 3 compared with quartile 1. Conclusions We found that in patients with acute ischemic stroke, ccPWV was positively related to the degree of IAC. Future longitudinal cohort studies may help to identify the potential role of IAC in the progression of cerebral arterial stiffness.

OBJECTIVE：To s ystematically review the economics of osimertinib for advanced non-small cell lung cancer （NSCLC），and to provide the reference for clinical application and healthcare decision makers. METHODS ：Retrieved from PubMed，Embase，the Cochrane L ibrary，Health Technology Assessment ，CNKI，Wanfang database ，VIP，CBM，etc.， pharmacoeconomic studies on osimertinib in the treatment of advanced NSCLC were collected from the inception to Apr. 2020. After screening and extracting relevant data ，the quality of the included studies was evaluated by using the Quality of Health Economics Studies （QHES），and the economic research results of the included literatures were systematically evaluated by using descriptive analysis method. RESULTS & CONCLUSIONS ：A total of 10 studies from 7 different countries were included ；QHES scores of the included literatures were 73-93，with an average of 86.8，and the quality of the researches was generally high. All the 10 studies were cost-effectiveness analysis ，including 6 first-line treatment ，4 second-line treatment. Six studies reported the cost discount rate ；only one study used the cost of osimertinib after price reduction for evaluation and analysis. Compared with other epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKI），six studies from different countries showed that osimertinib as the first-line treatment drug had no cost-effectiveness advantage ；cost-effectiveness of second-line treatment of osimertinib was controversial ，compared to chemotherapy. For advanced NSCLC patients ，the second-line treatment of osimertinib after the national centralized negotiation of price reduction has a more cost-effectiveness advantage in China ’s medical service system，while the first-line treatment of osimertinib before price reduction does not have this advantage compared with other EGFR-TKI drugs.

Objective:To explore the expression and clinical significance of mucin 5B in patients with primary intrahepatic bile duct stones (PHL) after hepatectomy.Methods:Collected the bile duct mucosa of 48 patients with intrahepatic bile duct stones (PHL group) and 16 patients with non-calculous benign liver disease (control group) who underwent hepatectomy in the Third Affiliated Hospital of Wenzhou Medical University from January 2014 to January 2019, Bile duct wall, bile and venous blood. The preoperative bile and serum indexes of the two groups were compared. Immunohistochemical staining was used to examine the expression of mucin 1 and mucin 5B in the bile duct wall, and the bile duct wall was examined pathologically by HE routine staining. With mucin 1 as a positive control and β-actin as an internal reference gene, real-time PCR was used to examine the mRNA expression levels of mucin 1 and mucin 5B in the bile duct mucosa. Pearson correlation analysis was used to analyze the correlation of variables within the PHL group.Results:The preoperative serum lipid indexes in the PHL group were higher than those in the control group, while the total bile acid concentration [(181.5±18.2) mmol/L vs. (192.1±22.5) mmol/L] and the molar percentage of bile acid [(80.7±1.6)% vs. (89.7±1.0)%] is lower than the control group, the difference is statistically significant ( P<0.05). The expression of mucin 1 mRNA in the PHL group was higher than that in the control group, but the difference was not statistically significant ( P>0.05). The expression of mucin 5B mRNA in the PHL group was significantly higher than that in the control group [(0.94±0.12) vs. (0.73±0.24)], the difference was statistically significant ( P<0.05); The increased expression of bile duct mucin 5B mRNA was negatively correlated with the level of total bile acids in bile ( r=-0.4, P<0.05). Conclusions:The increased expression of mucin 5B is closely related to PHL, which may be related to the promotion of bile acid absorption by the bile duct mucosal epithelium, which causes mucin to secrete into the bile in large quantities, leading to the formation of stone-causing bile.