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.

Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

OBJECTIVE: To investigate the current status of long-term quality of life in patients with severe acute pancreatitis (SAP) who have been cured and discharged, and to analyze the influencing factors affecting long-term quality of life in SAP cured patients after discharge. METHODS: A retrospective collection was conducted. Patients who were received standardized treatment before being cured and discharged from the hospital admitted to the first department of critical care medcine of the Second Affiliated Hospital of Anhui Medical University from January 2017 to December 2023 were enrolled. According to the 36-item short form health survey scale (SF-36) score, patients were divided into high score group (high quality of life, the top 50% of patients with total SF-36 score) and low score group (low quality of life, the bottom 50% of patients with total SF-36 score). The gender, age, history of hypertension and diabetes, etiology of pancreatitis, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), CT severity index (CTSI), laboratory indicators such as C-reactive protein (CRP), procalcitonin (PCT), blood glucose, and triglycerides upon admission, use of vasoactive drugs, non-invasive/high-flow ventilation, invasive ventilation, retroperitoneal puncture and drainage, open pancreatic surgery treatment and secondary infection during hospitalization were collected, as well as the retention of abdominal drainage tubes at discharge from hospital. Distribute follow-up questionnaires or telephone follow-up surveys through WeChat and Question Star programs to investigate the pancreatic secretion function, chronic abdominal pain, and recurrence of pancreatitis of patients after discharge. Multivariable Logistic regression was used to analyze the relevant factors affecting the long-term quality of life of cured patients with SAP. RESULTS: A total of 86 patients were ultimately enrolled. There were 43 patients in both the high and low score groups. Among 86 patients, 20 experienced acute pancreatitis recurrence, with a recurrence rate of 23.26%. Twenty-two (25.58%) experienced chronic abdominal pain after discharge, and 5 patients (5.81%) needed medication to relieve pain. Thirty-three patients (38.37%) had pancreatic exocrine dysfunction after discharge, characterized by abdominal distension, constipation or diarrhea. Twenty-two patients (25.58%) suffered from pancreatic endocrine dysfunction, and were diagnosed with diabetes. Univariate analysis showed that compared with the high score group, the low score group had more patients with hypertension, initial renal dysfunction, initial severe metabolic acidosis, initial serum calcium < 2.0 mmol/L, blood glucose > 11.1 mmol/L and cultured Gram positive bacteria (from blood/body fluid/pancreatic necrotic tissue) during treatment (48.84% vs. 16.28%, 60.47% vs. 32.56%, 18.60% vs. 4.65%, 88.37% vs. 62.79%, 55.81% vs. 30.23%, 34.88% vs. 13.95%), had higher CTSI score (6.60±1.61 vs. 5.77±1.32), lower hemoglobin level at discharge (g/L: 102.30±18.78 vs. 110.72±16.68), and a lower proportion of etiological interventions after discharge (34.88% vs. 67.44%), the differences were statistically significant (all P < 0.05). Multivariate Logistic regression analysis showed that hypertension [odds ratio (OR) = 4.814, 95% confidence interval (95%CI) was 1.196-19.378], initial serum calcium < 2.0 mmol/L (OR = 6.688, 95%CI was 1.321-33.873) and initial blood glucose > 11.1 mmol/L (OR = 6.473, 95%CI was 1.399-29.950) were risk factors for long-term quality of life in cured SAP patients (all P < 0.05), while post discharge prophylactic intervention was a protective factor for long-term quality of life (OR = 0.092, 95%CI was 0.020-0.425, P < 0.01). CONCLUSIONS Cured SAP patients have varying degrees of impaired secretion function and the possibility of recurrence of acute pancreatitis. Hypertension, initial serum calcium < 2.0 mmol/L and blood glucose > 11.1 mmol/L are independent influencing factors for low long-term quality of life in cured SAP patients. Prevention and intervention targeting the etiology of pancreatitis after discharge can improve the long-term quality of life of cured SAP patients.
Humans ; Quality of Life ; Retrospective Studies ; Pancreatitis/therapy* ; Patient Discharge ; Male ; Female ; Middle Aged ; APACHE ; Adult ; Acute Disease ; Aged

Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

ObjectiveTo observe the clinical effect of Jieyu Qingxin formula granules combined with remote interactive cognitive behavioral therapy for insomnia （CBT-I） on chronic insomnia of liver depression and fire-turning type. MethodThis study was a prospective randomized controlled trial. 120 patients with chronic insomnia of liver depression and fire-turning type in Lu'an traditional Chinese medicine Hospital from January 2022 to June 2023 were selected as objects. They were randomly divided into two groups，with 60 cases in each group. The control group received remote interactive CBT-I. The observation group was treated with Jieyu Qingxin formula granules on the basis of the control group. Intervention treatment lasted for four weeks，and observation lasted for six weeks. Comparison of data of each group：clinical efficacy，changes in traditional Chinese medicine （TCM） syndrome score before and after treatment，changes in insomnia severity index （ISI） score，self-rating depression scale （SDS） and self-rating anxiety scale （SAS） score changes，total sleep time，wake time，sleep latency，sleep efficiency， Actigraphy sleep parameter value changes，serum neuron specific enolase （NSE） ，adenosine，dopamine （DA）， 5-hydroxytryptamine （5-HT） level changes，and adverse reactions. ResultThe total effective rate in the observation group （92.45%，49/53） was higher than that in the control group（76.92%，40/52）， and the difference was statistically significant（χ²=4.711 1，P<0.05）. After treatment，TCM syndrome score，ISI score，SAS score， and SDS score were decreased in all groups. The total sleep time was extended，and wake time and sleep latency were shortened. The sleep efficiency was increased，but the NSE and DA levels were decreased. Adenosine and 5-HT levels were increased in all groups（P<0.05）. After treatment，compared with the control group，the observation group had lower TCM syndrome score，ISI score，SAS score， and SDS score，longer total sleep time，higher sleep efficiency，shorter wake time and sleep latency，lower NSE and DA levels， and higher adenosine and 5-HT level （P<0.05）. There was one case of nausea in the observation group and no adverse reaction in the control group during treatment. There was no significant difference between the two groups. ConclusionBy reducing NSE and DA and increasing the levels of 5-HT and adenosine，the anxiety （SAS score） and depression （SDS score） of patients can be improved， so as to improve their sleep and effectively treat chronic insomnia of liver depression and fire-turning type.

Objective: To examine the mediating effects of mindfulness level on resilience and symptoms of anxiety and depression among healthcare workers, so as to provide the reference for developing effective psychological intervention. Methods: The clinical doctors, nurses and public health professionals were selected using the stratified random cluster sampling method from hospitals, disease prevention and control centers, and health departments in five cities in Shandong Province, including Qingdao, Jinan, Rizhao, Jining and Liaocheng in January 2023. Basic information, mindfulness level, resilience and symptoms of anxiety and depression among healthcare workers were collected using general demographic questionnaires, the 5-item Mindful Attention Awareness Scale, 10-item Connor-Davidson Resilience Scale, Generalized Anxiety Disorder Scale and Patient Health Questionnaire, respectively. The Process program was used to analyze the mediating effects of mindfulness level on resilience and symptoms of anxiety and depression. Results: A total of 1 836 healthcare workers were investigated, including 472 males (25.71%) and 1 364 females (74.29%), and the median age was 39 (interquartile range, 12) years. There were 629 clinical doctors (34.26%), 963 nurses (52.45%) and 244 public health professionals (13.29%). The median scores of mindfulness level and resilience were 22 (interquartile range, 7) and 20 (interquartile range, 4) points, respectively. The detection rates of anxiety and depression symptoms were 49.78% and 72.28%, respectively. The mediation analysis showed that mindfulness level exerted a partial mediating effect between resilience and anxiety symptoms (β=-0.510, P<0.001), with a direct effect value of -0.130 and a mediating effect value of -0.046, and the mediating effect accounted for 26.14% of the total effect; mindfulness level also exerted a partial mediating effect between resilience and depression symptoms (β=-0.575, P<0.001), with a direct effect value of -0.120 and a mediating effect value of -0.052, and the mediating effect accounted for 30.23% of the total effect. Conclusion Mindfulness level plays a mediating effect between resilience and symptoms of anxiety and depression among healthcare workers.

Objective:To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction

Objective To investigate the expression and prognostic significance of serum protease C1 inhib-itor(SERPING1)and plasminogen activator inhibitor type 1(SERPINE1)in patients with sepsis.Methods A total of 132 patients with sepsis treated in the hospital from March 2018 to March 2020 were se-lected as the sepsis group.According to whether they died within 28 days of admission,they were divided into a death group(n=34)and a survival group(n=98).Enzyme linked immunosorbent assay was used to detect the expression of serum SERPING1 and SERPINE1.Multivariate Logistic regression model and receiver oper-ating characteristic curve were used to study the value of serum SERPING1 and serpine1 in evaluating the prognosis of patients'death.Results[Compared with the control group,serum SERPING1(331.12±51.80 ng/L vs.639.04±91.12 ng/L)was lower and serum serpine1(412.67±64.84 ng/L vs.42.33±10.32 ng/L)was higher in the sepsis group,and the differences were statistically significant(P＜0.05).[Compared to the survival group,the levels of serum SERPINE1,procalcitonin,C-reactive protein,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score in the death group were higher,while serum SERPING1 was lower,and the differences were statistically significant(all P＜0.05).Serum SERPING1 showed negative correlation with APACHE Ⅱ and SOFA scores(r=-0.779,-0.653,P＜0.05),while serum SERPINE1 showed positive correlation with APACHE Ⅱ and SO-FA scores(r=0.740,0.685,P＜0.05).APACHE Ⅱ score,SOFA score,and serum SERPINE1 were risk fac-tors affecting the prognosis of sepsis patients,while serum SERPING1 was a protective factor.The area under the curve of serum SERPING1 and SERPINE1 combined for the evaluation of the death in sepsis patients was 0.938(95％CI:0.893-0.968),which was significantly higher than 0.860(95％CI:0.812-0.899)and 0.838(95％CI:0.781-0.868)of the single detection,and the differences were statistically significant(Z=3.861,4.015,P＜0.001).Conclusion The elevated levels of serum SERPING1 and SERPINE1 in patients with sepsis are related to the severity of the patient's condition.The combination of the two has high prognos-tic value for sepsis patients.