Background Injury poses a serious threat to human health. As global warming continues to intensify, there is an urgent need to explore the impact of temperature changes on injury deaths. However limited research has focused on this issue. Objective To investigate the relationship between daily mean temperature change (Tm) and injury death, as well as to estimate the associated future death burden in Hunan Province. Methods We employed an individual-level, time-stratified case-crossing design to establish a conditional logistic regression model to analyze the exposure-response relationship between daily mean temperature change and injury death in Hunan Province from 2013 to 2018. Consequently, we conducted subgroup analysis of gender, age group, and injury type. Finally, we estimated the excess burden of injury death attributable to temperature changes under a sustainable development path [low emission scenario (SSP1-2.6)], regional competition path [high emission scenario (SSP3-7.0)], or fossil fuel development path [very high emission scenario (SSP5-8.5)]. Results The study collected 155577 injury deaths in Hunan Province. The results indicated that for each 1 ℃ increment in daily mean temperature, the cumulative excess risk (CER) of injury mortality among Hunan residents increased by 0.71% (95%CI: 0.53%, 0.90%). Notably, the CER for intentional injuries (1.06%, 95%CI: 0.51%, 1.61%) was higher than that for unintentional injuries (0.66%, 95%CI: 0.46%, 0.87%). Warmer temperatures were positively associated with CER of mortality due to drowning, falls, transport injuries, assaults, and suicides, while they were negatively associated with mortality due to poisoning. Compared with 2010–2019, for 2090–2099, the excess mortality rate (EMR) due to ambient temperature increase in Hunan Province under the SSP5-8.5 scenario (14.62/100000, 95%CI: 10.81/100000, 18.40/100000) would be higher than that of the SSP3-7.0 scenario (10.28/100000, 95%CI: 7.58/100000, 12.97/100000) and the SSP1-2.6 scenario (3.35/100000, 95%CI: 2.46/100000, 4.23/100000); the EMR would be around 2.5 times among men (20.64/100000, 95%CI: 14.44/100000, 26.8/100000) than that among women (8.33/100000, 95%CI: 3.98/100000, 12.6/100000). Among unintentional injuries, the leading contributors to EMR would be drowning (4.46/100000), falls (3.96/100000), and transport injuries (2.96/100000). And among intentional injuries, the EMR for suicide (2.08/100000) would be higher than that for assault (0.47/100000). Conclusion Climate warming will increase the total burden of injury-related deaths among residents in Hunan Province, especially in the absence of effective mitigation strategies and measures. It is necessary to strengthen the prevention and control of severe injuries closely related to temperature changes, such as drowning, falls, traffic, and suicides injuries, in order to reduce injury deaths associated with climate change.

OBJECTIVES: Keratoconus (KC) is a progressive corneal ectasia disorder, arising from a myriad of causes including genetic predispositions, environmental factors, biomechanical influences, and inflammatory reactions. This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population. METHODS: Twenty-five patients with primary KC as well as 50 unrelated population-matched healthy controls, were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population. Sanger sequencing and whole-exome sequencing (WES) were used to analyze mutations in the zinc finger protein 469 (ZNF469) gene. Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis. RESULTS: Five novel heterozygous missense variants were identified in KC patients. Among them, 2 compound heterozygous variants, c.8986G>C (p. E2996Q) with c.11765A>C (p. D3922A), and c.4423C>G (p. L1475V) with c.10633G>A (p. G3545R), were determined to be possible pathogenic factors for KC. CONCLUSIONS Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population. These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
Adolescent ; Adult ; Female ; Humans ; Male ; Case-Control Studies ; China/ethnology* ; Exome Sequencing ; Genetic Predisposition to Disease ; Keratoconus/genetics* ; Mutation ; Mutation, Missense ; Transcription Factors/genetics* ; East Asian People/genetics*

Objective:To assess the effect of joint exposure to multiple air pollutants on sleep structure in patients with stable chronic obstructive pulmonary disease (COPD), identify key air pollutants, and analyze potential influencing factors.Methods:In this panel study, 92 stable COPD patients were recruited. From March 2021 to September 2023 in Beijing, all participants completed 254 nights of sleep monitoring. The total sleep duration, light sleep duration, deep sleep duration and rapid eye movement sleep duration and their respective proportions in total sleep duration were recorded. The exposure levels of fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), ozone (O 3), sulfur dioxide (SO 2), and carbon monoxide (CO) were estimated based on the infiltration factor method and time-activity logs of participants. To assess the lag effect of air pollutants, moving average concentrations of air pollutants from 0-1 day to 0-3 months were calculated. The linear mixed-effect model and Bayesian kernel machine regression (BKMR) model were used to assess the single and joint effects of air pollutants on sleep structure parameters in COPD patients, respectively. Results:All six types of air pollutants were associated with changes in sleep structure, manifesting as an increase in total sleep duration and light sleep proportion and a reduction in deep sleep proportion. The effects of O 3 were strongest at lag 0-6 days, while other air pollutants were at lag 0-3 months. Joint exposure to multiple air pollutants exerted significant joint effects on sleep structure, and NO 2 was identified as the dominant pollutant. NO 2 had a posterior inclusion probability (PIP) greater than 0.5 for light sleep proportion (PIP=0.691) and deep sleep proportion (PIP=0.957). With an interquartile range (IQR) increase of 8.6 μg/m 3 in NO 2 at lag 0-3 months, the light sleep proportion increased by 10.5% (95% CI: 2.2%-19.4%), and the deep sleep proportion decreased by 19.5% (95% CI:-30.6%- -6.8%). Conclusion:Joint exposure to air pollutants is associated with changes in sleep structure in stable COPD patients, and NO 2 may be a key pollutant.

Glycogen storage disease type Ⅱ,also known as Pompe disease,is an autosomal recessive metabolic myopathy with pulmonary hypertension as a rare complication.We reported a case of pulmonary hypertension in adult with late-onset glycogen storage disease type Ⅱ.Her arterial blood gas results indicated type Ⅱ respiratory failure,lung function indicated severe restricted ventilation dysfunction,sleep monitoring indicated severe sleep apnea hypopnea,severe nocturnal hypoxemia,echocardiography-derived systolic pulmonary pressure was 62 mmHg(1 mmHg=0.133 kPa),electromyography indicated myogenic lesion,and whole exon sequencing indicated GAA gene mutation.Supportive therapy and enzyme replacement therapy are applied in this patient.

Objectives:To observe the effectiveness and safety of recombinant human brain natriuretic peptide(rhBNP)for the treatment of patients with right heart failure caused by pulmonary arterial hypertension(PAH).Methods:A total of 421 patients with right heart failure caused by PAH who were hospitalized in Fuwai Hospital from January 2019 to June 2024 were retrospectively included in this study.All patients were treated with rhBNP on top of conventional therapy.24 h urine volume,body weight,liver and renal function index,electrolyte,uric acid,red blood cell distribution width(RBCDW),cardiac function,blood pressure and heart rate before and after the treatment of rhBNP were compared.Clinical symptoms,signs and the occurrence of adverse events during treatment were also observed.Results:Compared with baseline,after treatment with rhBNP,the 24 h urine volume increased.The levels of body weight,transaminase,total bilirubin,direct bilirubin,uric acid,RBCDW,systolic blood pressure,heart rate,and N-terminal pro-B-type natriuretic peptide significantly decreased(all P<0.05).There were no statistically significant differences in the levels of serum creatinine,and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio(both P>0.05).Dyspnea and lower limbs edema were improved in 75.2%cases(227/302)and 66.9%cases(281/420)respectively.The incidence of adverse events and severe adverse events during rhBNP treatment were 1.2%(5/421)and 0.5%(2/421)respectively.Conclusions:Adding rhBNP on top of standard medication can effectively increase 24 h urine volume,reduce body weight,improve some prognostic indicators,improve the clinical symptoms and signs of heart failure without negatively affecting the renal function in right heart failure patients caused by PAH.Blood pressure should be closely monitored during the treatment process.

Objective:To develop CNN-Dinov2, a deep learning-based automatic classification model for Gram-stained images, enabling rapid diagnosis of three prevalent Gram-negative bacilli in bloodstream infections: Escherichia coli ( E.coli), Klebsiella pneumoniae ( K.pneumoniae), and Pseudomonas aeruginosa ( P.aeruginosa). Methods:This evaluation study analyzed 1 425 Gram-stained microscopic images from patients with bloodstream infections at Houjie Hospital, in Dongguan City, collected between January 2023 and January 2024. The images, all positive for blood culture and identified as target strains, were categorized into Escherichia coli (419 images), Klebsiella pneumoniae (411 images), Pseudomonas aeruginosa (413 images), and other Gram-negative bacilli (182 images). They were randomly split into a training set (1 141 images), a validation set (141 images), and a test set (143 images) in an 8∶1∶1 ratio. A hybrid CNN-Dinov2 model was developed by integrating ResNet′s local feature extraction with Dinov2′s global pre-trained features, followed by a fully connected layer. The model was optimized by inputting the preprocessed images and adjusting parameters through loss calculation and backpropagation. AlexNet, Dinov2, and ResNet18 served as control models. The models′ classification performance was assessed using accuracy, precision, weighted F1 score, and recall rate, derived from the confusion matrix. The PR curve and AP value further evaluated each model′s classification capability across the four image categories. Results:The CNN-Dinov2 model achieved a training accuracy of 99.74%, a validation accuracy of 98.12%, and a validation loss of 0.070 6, demonstrating robust generalization without overfitting. Validation metrics revealed superior performance with an accuracy of 98.60%, precision of 98.65%, a weighted F1 score of 98.60%, and a recall rate of 98.60%, outperforming other models. The confusion matrix confirmed its strong classification capability, with the highest sum of diagonal values for identifying four types of bacteria. The macro average precision (AP) values under the precision-recall (PR) curves were all 1, indicating excellent discrimination across all categories. Overall, the CNN-Dinov2 model exhibited the best performance among the four models evaluated.Conclusion:This study successfully developed CNN-Dinov2, an automated classification model for Gram staining images. It offers valuable support for the rapid diagnosis of bloodstream infections caused by Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, demonstrating practical utility.

Objective:To assess the effect of joint exposure to multiple air pollutants on sleep structure in patients with stable chronic obstructive pulmonary disease (COPD), identify key air pollutants, and analyze potential influencing factors.Methods:In this panel study, 92 stable COPD patients were recruited. From March 2021 to September 2023 in Beijing, all participants completed 254 nights of sleep monitoring. The total sleep duration, light sleep duration, deep sleep duration and rapid eye movement sleep duration and their respective proportions in total sleep duration were recorded. The exposure levels of fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), ozone (O 3), sulfur dioxide (SO 2), and carbon monoxide (CO) were estimated based on the infiltration factor method and time-activity logs of participants. To assess the lag effect of air pollutants, moving average concentrations of air pollutants from 0-1 day to 0-3 months were calculated. The linear mixed-effect model and Bayesian kernel machine regression (BKMR) model were used to assess the single and joint effects of air pollutants on sleep structure parameters in COPD patients, respectively. Results:All six types of air pollutants were associated with changes in sleep structure, manifesting as an increase in total sleep duration and light sleep proportion and a reduction in deep sleep proportion. The effects of O 3 were strongest at lag 0-6 days, while other air pollutants were at lag 0-3 months. Joint exposure to multiple air pollutants exerted significant joint effects on sleep structure, and NO 2 was identified as the dominant pollutant. NO 2 had a posterior inclusion probability (PIP) greater than 0.5 for light sleep proportion (PIP=0.691) and deep sleep proportion (PIP=0.957). With an interquartile range (IQR) increase of 8.6 μg/m 3 in NO 2 at lag 0-3 months, the light sleep proportion increased by 10.5% (95% CI: 2.2%-19.4%), and the deep sleep proportion decreased by 19.5% (95% CI:-30.6%- -6.8%). Conclusion:Joint exposure to air pollutants is associated with changes in sleep structure in stable COPD patients, and NO 2 may be a key pollutant.

Glycogen storage disease type Ⅱ,also known as Pompe disease,is an autosomal recessive metabolic myopathy with pulmonary hypertension as a rare complication.We reported a case of pulmonary hypertension in adult with late-onset glycogen storage disease type Ⅱ.Her arterial blood gas results indicated type Ⅱ respiratory failure,lung function indicated severe restricted ventilation dysfunction,sleep monitoring indicated severe sleep apnea hypopnea,severe nocturnal hypoxemia,echocardiography-derived systolic pulmonary pressure was 62 mmHg(1 mmHg=0.133 kPa),electromyography indicated myogenic lesion,and whole exon sequencing indicated GAA gene mutation.Supportive therapy and enzyme replacement therapy are applied in this patient.

Objectives:To observe the effectiveness and safety of recombinant human brain natriuretic peptide(rhBNP)for the treatment of patients with right heart failure caused by pulmonary arterial hypertension(PAH).Methods:A total of 421 patients with right heart failure caused by PAH who were hospitalized in Fuwai Hospital from January 2019 to June 2024 were retrospectively included in this study.All patients were treated with rhBNP on top of conventional therapy.24 h urine volume,body weight,liver and renal function index,electrolyte,uric acid,red blood cell distribution width(RBCDW),cardiac function,blood pressure and heart rate before and after the treatment of rhBNP were compared.Clinical symptoms,signs and the occurrence of adverse events during treatment were also observed.Results:Compared with baseline,after treatment with rhBNP,the 24 h urine volume increased.The levels of body weight,transaminase,total bilirubin,direct bilirubin,uric acid,RBCDW,systolic blood pressure,heart rate,and N-terminal pro-B-type natriuretic peptide significantly decreased(all P<0.05).There were no statistically significant differences in the levels of serum creatinine,and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio(both P>0.05).Dyspnea and lower limbs edema were improved in 75.2%cases(227/302)and 66.9%cases(281/420)respectively.The incidence of adverse events and severe adverse events during rhBNP treatment were 1.2%(5/421)and 0.5%(2/421)respectively.Conclusions:Adding rhBNP on top of standard medication can effectively increase 24 h urine volume,reduce body weight,improve some prognostic indicators,improve the clinical symptoms and signs of heart failure without negatively affecting the renal function in right heart failure patients caused by PAH.Blood pressure should be closely monitored during the treatment process.

BACKGROUND:In most species,a bone defect that is longer than 1.5 or 2 times its diameter can be considered a critical bone defect,and when the bone defect volume reaches the critical value,it cannot heal on its own.Currently,there is no uniform standard for the size of critical-sized defects in the osteoporotic femoral condyle of rabbits.OBJECTIVE:To establish a rabbit model with different sizes of bone defects in the osteoporotic femoral condyle and to determine the critical-sized defects of osteoporotic femoral condyle in rabbits.METHODS:Thirty-six 3-month-old female New Zealand white rabbits were randomly divided into ovariectomy group(n=30)and sham operation group(n=6).Rabbits in the ovariectomy group underwent bilateral ovariectomy to establish an osteoporosis model,and then femoral condyle bone defect models of different diameters(diameters were 4,5,6,and 7 mm,and depths were 8 mm)were further established;rabbits in the sham operation group did not undergo ovariectomy.At 8 and 12 weeks after modeling,3 rats were randomly selected from each group for CT scanning and three-dimensional reconstruction to evaluate the healing of bone defects.Afterwards,samples were taken for gross observation and hematoxylin-eosin staining to observe the growth of new bone in the femoral condyle bone defect area.RESULTS AND CONCLUSION:(1)All rabbits survived and moved well after modeling of osteoporosis and femoral condyle bone defect.(2)At 12 weeks after osteoporosis modeling,dual-energy X-ray absorptiometry results showed that the bone mineral density of lumbar vertebrae in ovariectomy group was significantly lower than that in sham operation group(P＜0.05).Hematoxylin-eosin staining showed that the bone trabeculae in the ovariectomy group became thinner and sparse.The proportion of bone tissue area in the ovariectomy group was significantly lower than that in the sham operation group(P=0.00).Micro-CT results showed that the bone tissue parameters of the femoral condyle in the ovariectomy group were significantly different from those in the sham operation group(P＜0.05),and the ovariectomy group showed obvious characteristics of osteoporosis.(3)CT showed that the bone defect in the 4 mm and 5 mm diameter groups was basically completely repaired at 12 weeks after surgery.There was more new bone tissue in the 6 mm diameter group,but the central part of the bone defect was not completely repaired.A small amount of new bone tissue grew in the 7 mm diameter group,and the bone defect was obvious.(4)Gross observation at 12 weeks after surgery showed that the femoral condyle bone defect in the 4 mm and 5 mm diameter groups was completely repaired.Obvious depression was seen in the bone defect area of the 6 mm and 7 mm diameter groups,and the bone defect was not completely repaired.(5)Histological observation at 12 weeks after surgery showed that the bone defect area of the 4 mm and 5 mm diameter groups was completely filled with new bone,and the trabecular structure was irregular;while there were new trabeculae in the periphery of the 6 mm and 7 mm diameter groups,and the bone defect in the central area was still obvious.(6)The results showed that during the 12-week experimental observation period of osteoporotic femoral condyle defects in rabbits,under the condition of the same defect depth of 8 mm,femoral condyle defects with a diameter ≥ 6 mm could not heal on their own,while femoral condyle defects with a diameter＜6 mm were completely repaired.A diameter of 6 mm and a depth of 8 mm can be used as the critical bone defect value of osteoporotic femoral condyle in rabbits.