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.

ObjectiveTo investigate the effect of Shugan Quyu Jiedu prescription （SGQYJDF） on inducing ferroptosis in hepatocellular carcinoma cells based on the tumor protein 53 （p53）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodMHCC97H cells were divided into the blank serum group （10% blank serum medium）， SGQYJDF-containing serum low concentration group （5% SGQYJDF-containing serum and 5% blank serum medium）， SGQYJDF-containing serum medium concentration group （7.5% SGQYJDF-containing serum and 2.5% blank serum medium）， SGQYJDF-containing serum high concentration group （10% SGQYJDF-containing serum medium） and sorafenib group （sorafenib concentration of 10 μmol·L^-1 in 10% blank serum medium）. After 24 hours of intervention， the cell survival rate was detected by cell counting kit-8 （CCK-8） assay. The cell proliferation ability was detected by 5-ethynyl-2′-deoxyuridine （EdU） staining. The intracellular ferrous ion （Fe²⁺） level was detected by ferrous ion fluorescent probe （FerroOrange） staining. The intracellular malondialdehyde （MDA） and glutathione （GSH） levels were detected by colorimetric assays. The ultrastructure of mitochondria was observed by transmission electron microscopy. The expression levels of ferroptosis-related proteins p53， SLC7A11 and GPX4 were detected by Western blot. ResultIn terms of cell viability， compared with the blank serum group， the SGQYJDF group showed a dose-dependent decrease in the survival rate of MHCC97H cells. Effect of the medium and high concentrations of SGQYJDF on the survival rate of MHCC97H cells were significantly decreased （P<0.01）. Additionally， the results of the EdU assay showed that both the medium and high concentrations of SGQYJDF were able to inhibit the proliferation ability of MHCC97H cells （P<0.05， P<0.01）. Regarding the biochemical indicators of ferroptosis， compared to the blank serum group， the medium and high concentrations of SGQYJDF were able to dose-dependently increase the intracellular Fe²⁺ level （P<0.01）. The low， medium， and high concentrations of SGQYJDF were able to dose-dependently decrease the level of GSH in MHCC97H cells （P<0.01） and increase the level of MDA in the cells （P<0.05， P<0.01）. In terms of pathway-related protein expression， compared to the blank serum group， the medium and high concentrations of SGQYJDF could significantly increase the expression of p53 （P<0.01）. The low， medium， and high concentrations of SGQYJDF could significantly decrease the expression of GPX4 （P<0.01）. The high concentration of SGQYJDF could decrease the expression of SLC7A11 （P<0.01）. In terms of the cell morphology of ferroptosis， compared with the blank serum group， transmission electron microscopy revealed that the low concentration of SGQYJDF caused mitochondrial deformation， while the medium and high concentrations of SGQYJDF resulted in reduced mitochondrial volume， increased double-layer membrane density， and decreased mitochondrial cristae. These features were similar to those of sorafenib-induced ferroptosis. Furthermore， compared with the sorafenib group， the high concentration of SGQYJDF showed no statistically significant differences in cell survival rate， proliferation ability， Fe²⁺ level， MDA level， and GSH level. ConclusionThe results suggest that SGQYJDF may induce ferroptosis and inhibit proliferation in hepatocellular carcinoma MHCC97H cells by upregulating the expression of p53， suppressing the expressions of GPX4 and SLC7A11， downregulating the level of GSH， and leading to the accumulation of intracellular Fe²⁺ and MDA.

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.

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.

The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.

Objective:To investigate the association of exposure to PM 2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods:We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM 2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM 2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results:A 10 μg/m 3 increase in PM 2.5 exposure during pregnancy was associated with a decrease of 0.025 ( β=-0.025, 95% CI: -0.048- -0.001) in HC Z-score, 0.026 ( β=-0.026, 95% CI: -0.049- -0.003) in AC Z-score, and 0.028 ( β=-0.028, 95% CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% ( RR=1.085, 95% CI: 1.010-1.165) and 13.5% ( RR=1.135, 95% CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM 2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO 42-) and ammonium consistently correlated with decreased HC Z-score. SO 42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions:Our findings demonstrated that exposure to PM 2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.