The personalized patient preference predictor proposed in 2024 has sparked widespread discussion. It mainly integrates machine learning with fine-tuning large language models to extract patients’ medical preferences by training and analyzing patients’ personalized sample data， to achieve better treatment. Combined with the current research situation， this paper pointed out its application dilemma： that is， the risks of inductive and analogical reasoning trigger its technical dilemma in accurate prediction， process explanation， and functional evaluation， ultimately leading to the ethical dilemma of the reduction of subject autonomy. Its solution paths were also clarified， including introducing substantive induction theory and substantive analogy theory to ensure the validity of sample data； implementing technology integration， perspective change， and evaluation system construction to improve the accuracy of prediction； as well as clarifying the priority of human subject status to protect the patient’s subjective autonomy. These showed that the personalized patient preference predictor has important social value and practical significance.

BACKGROUND: Infertility is a burdensome, often overlooked condition. This study aimed to investigate the global distribution and trends in the burden of infertility from 1990 to 2021. METHODS: We obtained data on the prevalence and years lived with disability (YLDs) related to infertility from the Global Burden of Disease 2021 study and evaluated them by calculating the estimated annual percentage change in age-standardized rates. We investigated the relationship between sociodemographic index (SDI) and the burden of infertility on the global, regional, and national levels. RESULTS: In 2021, there were 143,261,562 female and 55,481,380 male infertility cases worldwide, respectively. In China, female and male infertility cases accounted for 23.59% and 21.47% of the global totals, reaching 33,795,944 and 11,909,889, respectively. Compared with 2019, the global number of female and male infertility cases increased by 5,286,227 in females and 2,017,271 in males. In contrast, China saw a decline in both female and male infertility cases, with reductions of 698,735 and 154,591, respectively. From 1990 to 2021, the age-standardized prevalence rate (ASPR) and age-standardized YLDs rate (ASYR) for female infertility both increased by 0.59% annually, whereas these two corresponding indicators for male infertility increased by 0.50% annually worldwide. The burden of female infertility was consistently higher than that of male infertility and demonstrated a faster rate of increase. East Asia had the highest ASPR and ASYR for female infertility, whereas Eastern Europe had the highest metrics for male infertility. A horizontal S-shaped association was observed between the SDI and ASPR and ASYR of infertility, with a rapid decline in the infertility burden when the SDI exceeded 0.7. CONCLUSIONS The global burden of infertility has increased over the years, with a higher burden on women and underdeveloped regions. These findings emphasize the need to prioritize healthcare for patients with infertility to address the rising burden.
Humans ; Female ; Male ; Global Burden of Disease ; Prevalence ; Infertility/epidemiology* ; Adult ; Infertility, Male/epidemiology* ; Persons with Disabilities/statistics & numerical data* ; Middle Aged ; Infertility, Female/epidemiology* ; China/epidemiology* ; Disability-Adjusted Life Years

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

BACKGROUND:It is of great significance to find new diagnostic markers of the disease and molecular targets for the treatment of the disease and the alleviation of organ injury.Ferroptosis is a newly discovered form of cell death.Overactivation of ferroptosis in animal models of sepsis is associated with the activation of inflammatory response and the injury of the liver,heart,kidney and other important organs,but the relationship between ferroptosis and bloodstream infection is not very clear. OBJECTIVE:To study the changes and biological significance of ferroptosis in a mouse model of blood stream infection induced by different bacteria. METHODS:Blood stream infection models induced by gram negative bacteria Escherichia coli,Klebsiella pneumoniae and gram positive bacteria Staphylococcus aureus and Enterococcus faecalis were established in SPF-grade ICR male mice,with 42 mice in each group.The mRNA expression levels of ferroptosis marker genes transferrin receptor 1 and glutathione peroxidase 4 in the liver,myocardium and kidney were detected at 0.5,1,3,6,12,24 and 48 hours after modeling.Another 18 SPF-grade ICR male mice were selected and randomly divided into dimethyl sulfoxide(DMSO)control group,DMSO+Klebsiella pneumoniae group,and Ferrostatin-1+Klebsiella pneumoniae group,with 6 mice in each group.In the latter two groups,animal models of Klebsiella pneumoniae bloodstream infection were established by tail vein injection of Klebsiella pneumoniae suspension,and 5 mg/kg Ferrostatin-1 and an equal dose of DMSO were given intraperitoneally 1 hour prior to the modeling of bloodstream infection,respectively.Serum levels of alanine aminotransferase,aspartate aminotransferase,blood creatinine,blood urea nitrogen,phosphocreatine kinase isoenzyme,lactate dehydrogenase,and mRNA expression levels of ferroptosis marker genes in various tissues were assayed at 6 hours after modeling. RESULTS AND CONCLUSION:After bloodstream infection modeling,the mRNA expression levels of transferrin receptor 1 in the liver,myocardium and kidney of bloodstream infection mice with different bacteria increased first and then decreased;and the mRNA expression level of glutathione peroxidase 4 decreased first,then increased,and reached the peak at 6 hours after modeling.The changes in transferrin receptor 1 and glutathione peroxidase 4 mRNA levels in bloodstream infection mice induced by gram-negative bacteria were more significant than those in blood stream infection mice induced by gram-positive bacteria,especially in bloodstream infection mice induced by Klebsiella pneumoniae.At 6 hours after bloodstream infection induced by Klebsiella pneumoniae,the levels of alanine aminotransferase,aspartate aminotransferase,serum creatinine,blood urea nitrogen,creatine phosphate kinase isoenzyme,lactate dehydrogenase in mice were significantly increased.Before modeling,Ferrostatin-1 intervention significantly reduced the levels of alanine aminotransferase,aspartate aminotransferase,serum creatinine,blood urea nitrogen,creatine phosphate kinase isoenzyme,and lactate dehydrogenase.All these findings indicate that the activation of ferroptosis in bloodstream infection mice induced by different bacteria is obvious,and the activation of ferroptosis in bloodstream infection mice induced by gram-negative bacteria is more obvious.Inhibition of iron death significantly attenuates liver,myocardial,and kidney injury in the mouse model of bloodstream infection induced by Klebsiella pneumoniae.

Objective To investigate the differences in blood pressure phenotypes,renal pathological changes,and related pathogenic pathways in genetically diverse hypertensive mice obtained from 13 strains.Methods The genotypes of Cckbr+/+,Cckbr+/-and Cckbr-/-were obtained by hybridization of 13 strains of genetically diverse mice with Cckbr-/-mice.Blood pressure was measured with a noninvasive blood pressure analysis system(BP-2000).The expression of CCKBR protein in mouse kidney tissue was detected by Western Blot,and the pathological changes in mouse kidney tissue were detected by hematoxylin-eosin(HE)staining and immunohistochemistry(IHC).The pathogenic pathways related to essential hypertension were screened by RNA sequencing.Results In three specific mouse strains(A/J,LOT,and FIM),the systolic blood pressure(SBP)was significantly different between the Cckbr-/-and Cckbr+/+groups.HE staining and IHC showed that hypertension caused a certain degree of renal injury in the mice.Gene Ontology(GO)and pathway enrichment analysis showed that differentially expressed genes were enriched in metabolic processes and circadian rhythm regulation.Conclusions Genetically diverse mice can effectively simulate the genetic background of the population and provide a new resource for studying the pathogenic genes related to essential hypertension.

Objective:To study the biological role and related mechanism of autophagy in acute lung injury (ALI) of hemorrhagic shock mice.Methods:According to random number table method, wild-type male C57BL/6 mice were divided into control group, ALI group, rapamycin group and 3-methyladenine (3-MA) group, with 8 mice in each group. Light chain 3 (LC3) gene knockout mice with C57BL/6 background were divided into LC3 knockout group and LC3 knockout+ALI group, with 8 mice in each group. Control group, ALI group, LC3 knockout group, LC3 knockout+ALI group were intraperitoneally injected with 2 mL/kg normal saline, rapamycin group was intraperitoneally injected with 3 mg/kg autophagy activator rapamycin, 3-MA group was intraperitoneally injected with 15 mg/kg autophagy inhibitor 3-MA, all of which were given for 3 consecutive days. 2 hours after the last administration, the hemorrhagic shock induced ALI model was established. 24 hours after modeling, the lung index was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissue and lung injury score was performed. The expressions of autophagy genes LC3-Ⅱ/LC3-Ⅰ and Beclin-1 in lung tissue were detected by Western blotting. The contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in lung tissue were detected according to the steps of the kit.Results:Compared with the control group, the lung tissue structure was destroyed and exudation increased, lung index, lung injury score, the expressions of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and the contents of TNF-α, IL-6 and MDA in lung tissue significantly increased in the ALI group. Compared with the ALI group, the structural damage and exudation of lung tissue were reduced in the rapamycin group, lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue decreased, while the expressions of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 in lung tissue increased [lung index: (7.56±0.39)% vs. (9.12±0.59)%, lung injury score: 3.04±0.58 vs. 9.32±2.14, TNF-α (ng/mg): 1.85±0.32 vs. 3.51±0.62, IL-6 (ng/mg): 1.61±0.32 vs. 2.52±0.44, MDA (nmol/mg): 1.03±0.16 vs. 1.88±0.24, LC3-Ⅱ/LC3-Ⅰ: 1.21±0.12 vs. 0.39±0.05, Beclin-1/β-actin: 1.10±0.12 vs. 0.58±0.06, all P < 0.05], while lung tissue structure damage was aggravated and exudation was further increased in the 3-MA group, lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue increased, the expressions of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 in lung tissue decreased [lung index: (10.44±0.62)% vs. (9.12±0.59)%, lung injury score: 11.59±2.28 vs. 9.32±2.14, TNF-α (ng/mg): 4.77±0.71 vs. 3.51±0.62, IL-6 (ng/mg): 3.44±0.52 vs. 2.52±0.44, MDA (nmol/mg): 2.71±0.42 vs. 1.88±0.24, LC3-Ⅱ/LC3-Ⅰ: 0.25±0.04 vs. 0.39±0.05, Beclin-1/β-actin: 0.21±0.03 vs. 0.58±0.06, all P < 0.05]. Lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue of LC3 knockout ALI mice were higher than those of wild-type ALI mice [lung index: (10.44±0.75)% vs. (9.12±0.59)%, lung injury score: 12.41±2.86 vs. 9.32±2.14, TNF-α (ng/mg): 4.85±0.72 vs. 3.51±0.62, IL-6 (ng/mg): 3.28±0.51 vs. 2.52±0.44, MDA (nmol/mg): 2.75±0.41 vs. 1.88±0.24, all P < 0.05]. Conclusion:Autophagy plays a protective role in ALI of hemorrhagic shock mice, and the related molecular mechanism is the inhibition of inflammatory response and oxidative stress response.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To analyze the risk factors for ankle varus deformity after McFarland fracture surgery in children.Methods:A total of 48 children with McFarland fracture who underwent surgical treatment in the Second General Hospital of Fuzhou from January 2015 to December 2022 were retrospectively analyzed, including 24 males and 24 females, aged 11.2±3.2 years (range, 2-14 years), 19 cases on the left side and 29 cases on the right side. Salter-Harris classification: 34 cases of type III and 14 cases of type IV. Causes of injuries: 28 cases of sports injuries, 15 cases of fall injuries, and 5 cases of car accident injuries. The time from injury to operation was 2.6±1.7 d (range, 1-7 d). The reduction methods included closed reduction in 38 cases and open reduction in 10 cases. Tibial internal fixation: 42 cases of hollow screws, 6 cases of Kirschner pins. There were 30 cases of combined fibula fracture, 20 cases were fixed with plate, 8 cases were fixed with Kirschner's pin, and 2 cases were not treated with internal fixation. The internal fixation survival time was 6.4±2.8 months (range, 1-12 months). The lateral distal tibial angle (LDTA) was used to determine whether the child had ankle varus deformity. The general data and perioperative indicators of the two groups were compared, and the indicators with statistically significant differences were included in binary logistic regression analysis to determine the independent risk factors for ankle varus deformity after McFarland fracture surgery in children. The receiver operating characteristic curve was drawn and the area under the curve of each independent risk factor was calculated.Results:All patients successfully completed the operation and were followed up for 39.2±21.8 months (range, 15-98 months). At the last follow-up, all the 48 children with McFarland fracture had bone union and the internal fixation was successfully removed, and 5 of them had ankle varus deformity. The LDTA of the affected side was 98.6°±4.8° (range, 94°-106°) in the ankle varus deformity group and 89.0°±0.8° (range, 87°-91°) in the non-ankle varus deformity group. The age of children in the ankle varus deformity group was 6.6±5.1 years, which was younger than that in the non-ankle varus deformity group (11.7±2.5 years), and the difference was statistically significant ( t=3.772, P<0.001). The survival time of internal fixation in the ankle varus deformity group was 4.4±2.2 months, which was shorter than that in the non-ankle varus deformity group (6.6±2.8 months), and the difference was statistically significant ( t=1.750, P=0.087). There was no significant difference in gender, side, cause of injury, fracture type, initial displacement distance, fibular fracture, time from injury to operation, reduction method, or fixation method between the two groups ( P>0.05). Age and duration of internal fixation were included in binary logistic regression analysis. The results showed that age ( OR=0.717, 95% CI: 0.543, 0.945, P=0.018) was an independent risk factor for postoperative ankle varus deformity in children with McFarland fracture. The receiver operating characteristic curve of independent risk factors predicting postoperative ankle varus deformity in children with McFarland fracture was drawn and the area under the curve was calculated. The results showed that the best cut-off value of age was 5.5 years, and the area under the curve was 0.807, and the prediction efficiency of the prediction model was good. Conclusion:Age<5.5 years is an independent risk factor for postoperative varus ankle deformity in children with McFarland fracture.

Objective:To investigate the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with Severe Acute Respiratory Infection (SARI) in Tianjin from 2015 to 2020.Methods:The study data were obtained from the Third Center Hospital of Tianjin, a designated sentinel hospital, from 2015 to 2020, with 1 597 SARI patients enrolled in this study. The clinical specimens of the research participants were subjected to respiratory multi-pathogen testing. HRSV-positive specimens were subtyped to analyze the differences in HRSV detection rates among cases of different age groups and periods and their mixed infection situations.Results:A total of 1 597 nasopharyngeal swabs were collected, with an HRSV detection rate of 4.20%. Among 67 HRSV-positive specimens, there were 19 pure HRSV-A nucleic acid-positive specimens, 19 pure HRSV-B nucleic acid-positive specimens and 29 mixed HRSV-A and HRSV-B nucleic acid-positive specimens. The difference in HRSV detection rate among different age groups was statistically significant ( P<0.05), and the HRSV detection rate in children under five years old was higher than that in other age groups. From 2016 to 2020, the detection rate of HRSV showed an increasing trend year by year. The HRSV detection rate of SARI cases was highest in the winter season, at 7.15%. There were 10 (14.93%) mixed positive cases for HRSV and other viruses, of which four were mixed positive for HRSV and influenza A. Conclusion:The incidence of HRSV in Tianjin exhibits an increasing trend from 2016 to 2020, peaking during the winter season, with children under five years old constituting a high-risk demographic for HRSV infection.

Objective:To investigate the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with Severe Acute Respiratory Infection (SARI) in Tianjin from 2015 to 2020.Methods:The study data were obtained from the Third Center Hospital of Tianjin, a designated sentinel hospital, from 2015 to 2020, with 1 597 SARI patients enrolled in this study. The clinical specimens of the research participants were subjected to respiratory multi-pathogen testing. HRSV-positive specimens were subtyped to analyze the differences in HRSV detection rates among cases of different age groups and periods and their mixed infection situations.Results:A total of 1 597 nasopharyngeal swabs were collected, with an HRSV detection rate of 4.20%. Among 67 HRSV-positive specimens, there were 19 pure HRSV-A nucleic acid-positive specimens, 19 pure HRSV-B nucleic acid-positive specimens and 29 mixed HRSV-A and HRSV-B nucleic acid-positive specimens. The difference in HRSV detection rate among different age groups was statistically significant ( P<0.05), and the HRSV detection rate in children under five years old was higher than that in other age groups. From 2016 to 2020, the detection rate of HRSV showed an increasing trend year by year. The HRSV detection rate of SARI cases was highest in the winter season, at 7.15%. There were 10 (14.93%) mixed positive cases for HRSV and other viruses, of which four were mixed positive for HRSV and influenza A. Conclusion:The incidence of HRSV in Tianjin exhibits an increasing trend from 2016 to 2020, peaking during the winter season, with children under five years old constituting a high-risk demographic for HRSV infection.