BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.

OBJECTIVE To construct a refined intelligent management platform for the supply chain of hospital preparations and to evaluate its implementation effectiveness.METHODS Machine learning and classical time series model were used to predict the demand for hospital preparations. Based on the prediction results， an intelligent management platform was constructed around each link of the supply chain of hospital preparations， which included three functional modules： intelligent auxiliary decision-making， daily expiry date monitoring， and intelligent push and continuous improvement. By comparing indicators such as the mean of average inventory turnover days of each preparation， average monthly expired and scrapped amount， and average clinical satisfaction before and after the application of the platform in the First Affiliated Hospital of Soochow University， the application effectiveness was evaluated from three dimensions: cost control， operational efficiency， and pharmaceutical care service quality.RESULTS The constructed intelligent management platform could automatically generate dynamic inventory grading alerts， production plan suggestions， material procurement suggestions， and expiry date alerts， and intelligently push them to relevant responsible persons. Compared with before the application， in terms of cost control， the mean of average inventory turnover days of each preparation was shortened from 64.1 days to 48.4 days， and the average monthly expired and scrapped amount was reduced from 1 973 yuan to 1 369 yuan； in terms of operational efficiency， the average time for production plan formulation was shortened from 120 min to 60 min， and the average lag days of expiry date alert information was shortened from 15 days to 0.5 days； in terms of pharmaceutical care service quality， the average clinical satisfaction increased from 85.4% to 94.6%.CONCLUSIONS The refined intelligent management platform for the supply chain of hospital preparations has been successfully constructed， which can assist managers in decision-making regarding production plan formulation， procurement， and disposal of near-expiry preparations and materials， thereby achieving the purpose of cost reduction and efficiency improvement.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

In recent years, there has been a significant surge in the prevalence of myopia at younger ages in China. Numerous studies have investigated methods for preventing and controlling myopia, including orthokeratology, low-concentration atropine eye drops, light therapy, posterior scleral reinforcement, and traditional Chinese medicine. These approaches can modulate choroidal thickness, blood flow, and target various molecular mechanisms. Orthokeratology and low-concentration atropine demonstrate a thickening effect on the choroid and regulate choroidal blood flow; the use of multi-point defocus control lenses also shows promise in thickening the choroid; the influence of light and light feeding therapy on myopia prevention and control is also reflected in the choroidal thickness and blood flow; and the traditional Chinese medicine has shown good prospect in influencing the microstructure of the choroid for myopia prevention and control. However, the long-term effects of various prevention and control measures on the choroid still need to be explored with a large sample size. This article provides an overview of various methods used to regulate the choroid and prevent myopia. The mechanisms by which these interventions act on the choroid are described to provide new insights and identity novel clinical strategies for myopia management.

AIM:To observe the effects of Huangqi-Danggui mixture(HQDG)on the pyroptosis of brain tis-sues in rats with middle cerebral artery occlusion/reperfusion(MCAO/R),and to explore the mechanism of neuroprotec-tion provided by HQDG.METHODS:Sixty-four SD rats were randomly divided into 4 groups:sham group,model group,HQDG group,and Xuesaitong(XST)group.The infarct volume of brain tissues was observed by 2,3,5-triphenyl-tetrazolium chloride staining,while hematoxylin-eosin staining was used to observe the pathological changes of brain tis-sues.Immunofluorescence was employed to assess the expression of nucleotide-binding oligomerization domain-like recep-tor protein 3(NLRP3),cleaved caspase-1 and gasdermin D(GSDMD)in the ischemic penumbra of brain tissues.The se-rum levels of interleukin-1β(IL-1β)and IL-18 were measured using ELISA.Western blot was used to detect NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),IL-1β and IL-18 in brain tissues.RESULTS:Compared with sham group,the neurological deficit scores of the rats in model group were significantly increased(P<0.01),while those in HQDG and XST groups were significantly reduced compared with model group(P<0.01).The cerebral infarct volume ratio was significantly reduced in HQDG and XST groups compared with model group(P<0.01).The pathological damage of brain tissue in HQDG and XST groups was significantly reduced compared with model group.The positive rates of NLRP3,cleaved caspase-1 and GSDMD in the ischemic penumbra of brain tissues were significantly decreased in HQDG group compared with model group(P<0.01).The expression of pyrop-tosis-related proteins,NLRP3,cleaved caspase-1 and ASC,in the ischemic penumbra of brain tissues was significantly el-evated in model group compared with sham group(P<0.01),and significantly decreased in HQDG group compared with model group(P<0.01).The serum levels of IL-1β and IL-18 were significantly increased in model group compared with sham group(P<0.01),and significantly reduced in HQDG group compared with model group(P<0.01).CONCLU-SION:The HQDG effectively attenuates brain tissue injury in rats with MCAO/R,and its mechanism may be related to the inhibition of neural cell pyroptosis.

Objective:To assess the application value of one-hour post-load glucose (1hPG) for detecting prediabetes among individuals with high risk of type 2 diabetes mellitus (T2DM).Methods:The study was conducted between August 2023 and January 2024, and individuals with a high risk of T2DM were invited to receive an oral glucose tolerance test (OGTT), structural questionnaires, physical measurements, and other biochemical examinations. The fasting, one-, and two-hour glucose and insulin were tested. According to the 1hPG cut point on hyperglycemia suggested by International Diabetes Federation (IDF), normal glucose tolerance (NGT) and prediabetes were further divided into two subgroups, respectively, i.e., NGT with 1hPG<8.6 mmol/L (NGT-1hPG-normal), NGT with 1hPG≥8.6 mmol/L (NGT-1hPG-high), prediabetes with 1hPG<8.6 mmol/L (PDM-1hPG-normal), and prediabetes with 1hPG≥8.6 mmol/L (PDM-1hPG-high). The insulin release curve was drawn by the groups as above. Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR), and β-cell secretory function was evaluated by homeostasis model assessment for β cell function (HOMA-β)/HOMA-IR. Spearman rank correlation analysis was used to calculate the correlation coefficients among 1hPG, 2hPG and HOMA indices, and Steiger′s Z test was used to compare the difference between two correlation coefficients. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to assess the accuracy of 1hPG for detecting prediabetes. Results:A total of 2 469 subjects consisting of 1 485 men (60.1%) and 984 (39.9%) women, with a mean age of (45.76±6.20) years, of which 1 844 (74.7%) had 1hPG≥8.6 mmol/L. The prevalence of 1hPG≥8.6 mmol/L was 46.8%, 93.0% and 99.8% in individuals with NGT, prediabetes and newly diagnosed T2DM, respectively ( χ 2=763.78, P<0.001). The insulin release curve showed that insulin secretion increased rapidly in subjects with NGT-1hPG-high, and peaked at one hour, then decreased rapidly, with a significantly higher level of one- and two-hour insulin than those with NGT-1hPG-normal ( P<0.001). Compared to individuals with NGT-1hPG-normal, the counterparts with NGT-1hPG-high exhibited higher HOMA-IR and lower adjusted HOMA-β ( P<0.001). Spearman rank correlation analysis showed that the correlation coefficient of 1hPG with HOMA-IR was similar to the correlation coefficient of 2hPG with HOMA-IR (0.493 vs. 0.480, P=0.550), while the correlation of 1hPG with adjusted HOMA-β was significantly stronger than that of 2hPG (-0.692 vs. -0.587, P<0.001). Excluding patients with T2DM, according to the cut point recommended by IDF, the AUC of 1hPG≥8.6 mmol/L for detecting prediabetes was 0.731 (95% CI: 0.714-0.748), and the sensitivity and specificity were 0.930 and 0.532, respectively, with the kappa value of 0.45. Conclusion:1hPG is closely related to insulin resistance and islet function, and there′s substantial value for individuals with a high risk of T2DM to detect prediabetes by using the 1hPG cut points recommended by IDF.