Objective:To explore the diagnostic value of the combined detection of v-Kirsten Ras viral oncogene homolog(KRAS),transmembrane protein 243(TMEM243),cell division cycle protein 42(CDC42)and RAS like family 11 member B(RASL11B)for different types of Hashimoto's thyroiditis(HT).Methods:From January 2023 to December 2024,a total of 185 HT patients who received detection in Hebei Yanda Hospital were selected by using a random number table method,and they were divided into three groups according to HT type,which included the euthyroid HT group(65 cases),the hypothyroid HT group(60 cases)and the hyperthyroidism HT group(60 cases).Another 65 healthy individuals who underwent physical examination during the same period were selected as the healthy control group.An analyzer of enzyme-linked immunosorbent assay(ELISA)was used to measure and analyze the levels of KRAS,TMEM243,CDC42 and RASL11B in the four groups.Differences in autoantibody levels among different HT patients were compared.Logistic regression analysis was conducted to assess influence factors for HT.A nomogram model was constructed to realize visual presentation on the basis of the influence factors.Receiver operating characteristic(ROC)curves were adopted to assess the diagnostic efficacy of antibodies for subjects in the four groups.Results:The KRAS,TMEM243,CDC42 and RASL11B levels in the three HT groups were significantly higher than those in the healthy control group(F=906.962,840.078,830.290,846.182,P<0.05),respectively.Multivariate logistic regression analysis showed that KRAS,TMEM243,CDC42 and RASL11B were risk factors for HT(OR=4.071,1.424,1.026,1.031,P<0.05).The area under curve(AUC)of the ROC curve of the combined detection of four indicators of autoantibodies was 0.975,which sensitivity and specificity were respectively 94.05%and 92.31%.Conclusion:There were overexpression of KRAS,TMEM243,CDC42 and RASL11B in HT patients,especially,the overexpression of hyperthyroidism HT patients is more significant.The combined detection of the four indicators of autoantibody has favorable performance and clinical reference value in diagnosing HT.

Barrett's esophagus(BE),a precancerous state of esophageal adenocarcinoma,poses a major challenge for prevention and treatment owing to its complex mechanism of inflammation-cancer transformation and the lack of effective clinical treatment and torsion strategies.Building upon the"preventing disease progression"theory,this study aimed to address the critical clinical challenge of intercepting the pathological progression during the inflammation-cancer transformation of BE by proposing an innovative"two critical nodes-three stages"pathomechanism framework.The pathogenesis of BE originates from liver depression and qi stagnation.The pathological progression evolves through two critical nodes:liver depression transforming into heat and heat transforming into blood stasis,representing a three-stage evolutionary pattern of qi stagnation,heat transformation,and blood stasis formation.Acidic bile salts,acting as a pathogenic toxin,permeate the entire process and catalyze carcinogenesis.Based on this understanding,the therapeutic principles of"treatment from the liver"and"truncation and torsion"were established,emphasizing stage-specific interventions.For the qi stagnation stage,treatment focuses on soothing the liver and regulating qi,as well as moistening,harmonizing,and descending the qi.This is achieved by combining modified Chaihu Shugan Powder with Xuanfu Daizhe Decoction,while using pungent and drying herbs cautiously and supplementing them with light and floral herbs.In the heat transformation stage,the strategy aims to clear the liver and drain heat while protecting yin and harmonizing the stomach,employing modified Huaganjian combined with Yiguanjian and supplemented with Jinlingzi Powder to clear depressed fire.For the blood stasis formation stage,treatment involves activating blood and resolving stasis,combined with supporting healthy qi and removing toxins.This is achieved using a modified Gexia Zhuyu Decoction,supplemented with Liujunzi Decoction,and additions such as Radix Salviae Miltiorrhizae and turtle carapace to disperse nodules and reduce masses.This theoretical framework establishes a diagnostic and therapeutic model characterized by the integration of disease mechanisms with pathology and the mutual reference of macro-level signs with micro-level indicators.It provides a comprehensive clinical practice pathway,complete with principles,methods,formulas,and herbs,for the stage-specific interception of inflammation-cancer transformation in BE using traditional Chinese medicine.

Objective To identify potential biomarkers for proliferative diabetic retinopathy(PDR)using proteomics and transcriptomics data.Methods In this study,the proteomics dataset(PXD046630)and two transcriptomics datasets(GSE60436 and GSE102485)were derived from the aqueous humor samples and fibrovascular membranes of PDR patients,respectively.Differentially expressed genes(DEGs)were identified via R software,specifically the limma and edgeR pack-ages.The shared DEGs between PXD046630 and GSE60436 were analyzed via protein-protein interaction(PPI),Gene On-tology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.The key DEGs were validated in GSE102485 via receiver operating characteristic(ROC)curve analysis.A quantitative polymerase chain reaction(qPCR)assay was used to confirm the mRNA of these candidate biomarkers in human retinal microvascular endothelial cells(HRMECs)cultured in high glucose and low oxygen conditions.Results A total of 59 shared DEGs and 26 hub genes were identified from the PXD046630 and GSE60436 datasets.KEGG analysis revealed that six pathways,inclu-ding extracellular matrix-receptor interaction,proteoglycans in cancer,and complement and coagulation cascades,were enriched in 12 key DEGs.Fibronectin 1(FN1),tissue inhibitor of metalloproteinase 3(TIMP3),complement factor H(CFH),decorin(DCN),and lipoprotein receptor-related protein-2(LRP2)were identified as potential biomarkers on the basis of their AUC values being greater than 0.900(CI≥95％).The mRNA expression levels of FN1,CFH,and LRP2 were significantly increased in HRMECs cultured in high glucose and low oxygen conditions.Conclusion FN1,CFH,and LRP2 are potential biomarkers for PDR,and further studies are needed to explore their roles and therapeutic potential in PDR.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective:To explore the diagnostic value of the combined detection of v-Kirsten Ras viral oncogene homolog(KRAS),transmembrane protein 243(TMEM243),cell division cycle protein 42(CDC42)and RAS like family 11 member B(RASL11B)for different types of Hashimoto's thyroiditis(HT).Methods:From January 2023 to December 2024,a total of 185 HT patients who received detection in Hebei Yanda Hospital were selected by using a random number table method,and they were divided into three groups according to HT type,which included the euthyroid HT group(65 cases),the hypothyroid HT group(60 cases)and the hyperthyroidism HT group(60 cases).Another 65 healthy individuals who underwent physical examination during the same period were selected as the healthy control group.An analyzer of enzyme-linked immunosorbent assay(ELISA)was used to measure and analyze the levels of KRAS,TMEM243,CDC42 and RASL11B in the four groups.Differences in autoantibody levels among different HT patients were compared.Logistic regression analysis was conducted to assess influence factors for HT.A nomogram model was constructed to realize visual presentation on the basis of the influence factors.Receiver operating characteristic(ROC)curves were adopted to assess the diagnostic efficacy of antibodies for subjects in the four groups.Results:The KRAS,TMEM243,CDC42 and RASL11B levels in the three HT groups were significantly higher than those in the healthy control group(F=906.962,840.078,830.290,846.182,P<0.05),respectively.Multivariate logistic regression analysis showed that KRAS,TMEM243,CDC42 and RASL11B were risk factors for HT(OR=4.071,1.424,1.026,1.031,P<0.05).The area under curve(AUC)of the ROC curve of the combined detection of four indicators of autoantibodies was 0.975,which sensitivity and specificity were respectively 94.05%and 92.31%.Conclusion:There were overexpression of KRAS,TMEM243,CDC42 and RASL11B in HT patients,especially,the overexpression of hyperthyroidism HT patients is more significant.The combined detection of the four indicators of autoantibody has favorable performance and clinical reference value in diagnosing HT.

BACKGROUND:Ca2+expression in astrocytes has been found to be closely related to cognitive function,and the Ca2+signaling pathway regulated by inositol 1,4,5-trisphosphate receptors(IP3R2)and ryanodine receptor(RYR)2 receptors has become a hot spot in the study of cognitive disorder-related diseases. OBJECTIVE:To investigate the expression of Ca2+signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning,and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning. METHODS:C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group.An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group,and the same amount of air was inhaled in the control group.Behavioral and neuronal changes,astrocyte specific marker glial fibrillary acidic protein,IP3R2,RYR2 receptor and Ca2+concentration in astrocytes of the two groups were detected using Morris water maze,hematoxylin-eosin staining,western blot,immunofluorescence double labeling and Ca2+fluorescence probe at 21 days after modeling. RESULTS AND CONCLUSION:In the Morris water maze,the escape latency of the experimental group was significantly longer than that of the control group(P<0.05).Hematoxylin-eosin staining results showed that in the experimental group,the number of hippocampal pyramidal cells decreased,the cell structure was disordered,and the nucleus was broken and dissolved.Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus,and the expressions of IP3R2,RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group(P<0.05).Western blot analysis showed that the expressions of IP3R2,RYR2,and glial fibrillary acidic protein in the hippocampus of the experimental group were increased(P<0.05).Ca2+concentration in hippocampal astrocytes increased significantly in the experimental group(P<0.05).To conclude,astrocytes may affect Ca2+signals by mediating IP3R2 and RYR2 receptors,then impair the cognitive function of mice with carbon monoxide poisoning,and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.

OBJECTIVE: To observe the effects of enhanced rehabilitation on the prognosis of critically ill patients in the intensive care unit (ICU). METHODS: A single-center retrospective historical controlled study was conducted, patients admitted to the ICU of Peking University First Hospital from May 1, 2020, to April 30, 2021, and from October 1, 2021, to September 30, 2022 were enrolled. According to the different rehabilitation treatment strategies during different periods, patients were divided into the conventional rehabilitation group (patients receiving conventional rehabilitation treatment from May 1, 2020, to April 30, 2021) and the enhanced rehabilitation group (patients receiving the therapy of multidisciplinary team, ie medical care-rehabilitation-nursing care from October 1, 2021, to September 30, 2022). General data, acute physiology and chronic health evaluation II (APACHE II), and study endpoints were collected. Primary endpoints included rehabilitation-therapy rate, intervention time for rehabilitation, rehabilitation-related adverse events, and prognostic indicators such as (length of stay in hospital, length of stay in the ICU, and duration of mechanical ventilation). Secondary endpoints included incidence of deep vein thrombosis and hospital mortality. Kaplan-Meier curves were used to analyze cumulative discharge rates within 50 days. RESULTS: A total of 539 ICU patients were enrolled, with 245 in the conventional rehabilitation group and 294 in the enhanced rehabilitation group; 322 patients had an APACHE II score ≤ 15, while 217 patients had an APACHE II score > 15. Compared to the conventional rehabilitation group, the enhanced rehabilitation group demonstrated significantly higher rehabilitation-therapy rate [51.70% (152/294) vs. 11.43% (28/245)], earlier intervention time for rehabilitation [days: 2.00 (1.00, 3.00) vs. 4.00 (3.00, 7.00)]; shorter length of stay in hospital [days: 18.00 (12.00, 30.00) vs. 21.00 (13.00, 36.00)] and lower incidence of DVT [17.01% (50/294) vs. 24.08% (59/245)]. The differences were all statistically significant (all P < 0.05). There were no rehabilitation-related adverse events occurred in either group. Kaplan-Meier analysis demonstrated a significantly higher cumulative discharge rate within 50 days in the enhanced rehabilitation group compared to the conventional rehabilitation group [86.7% (255/294) vs. 82.9% (203/245); Log-Rank test: χ² = 4.262, P = 0.039]. Subgroup analysis showed that for patients with APACHE II score ≤ 15, the enhanced rehabilitation subgroup had higher rehabilitation-therapy rate [44.32% (78/176) vs. 6.16% (9/146), P < 0.05]. For patients with APACHE II score > 15, compared to the conventional rehabilitation group, the enhanced subgroup demonstrated higher rehabilitation-therapy rate [62.71% (74/118) vs. 19.19% (19/99), P < 0.05] and shorter length of stay in hospital [days: 20.50 (12.00, 31.25) vs. 26.00 (16.00, 43.00), P < 0.05]. CONCLUSIONS Enhanced rehabilitation therapy with medical care, rehabilitation and nursing care, improved rehabilitation-therapy rate, advanced time of rehabilitation treatment, reduced length of stay in hospital and incidence of deep vein thrombosis in critically ill patients, particularly benefited those with APACHE II score > 15. The enhanced rehabilitation was beneficial to the patient in the intensive care unit with safety and worth more investigation.
Humans ; Retrospective Studies ; Critical Illness/rehabilitation* ; Intensive Care Units ; Prognosis ; Length of Stay ; APACHE ; Historically Controlled Study ; Male ; Female ; Middle Aged ; Aged

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective To observe the effects of Bushen Antai Mixture on vascular recasting at the maternal-fetal interface in mice with recurrent spontaneous abortion(RSA)based on AMPK/ULK1/Beclin1 pathway.Methods CBA/J female mice and BALB/c male mice were caged at a ratio of 2:1 to establish normal pregnant mice(normal group),and CBA/J female mice and DBA/2 male mice were caged to establish RSA model.The RSA mice were randomly divided into model group,autophagy agonist group and TCM high-,medium-and low-dosage groups,with 10 mice in each group.From the first day of pregnancy,TCM high-,medium-and low-dosage groups were given Bushen Antai Mixture 35.1,11.7 and 3.9 g/kg by gavage respectively,and the normal group,model group and autophagy agonist group were given the same amount of normal saline by gavage for 15 days.The embryo development was observed and the embryo loss rate was calculated,the morphology of decidual tissue was observed by HE staining;the contents of vascular endothelial growth factor(VEGF)and vascular endothelial cadherin(VE-cadherin)in decidual tissue were detected by ELISA;the expressions of autophagy related proteins adenosine monophosphate-activated protein kinase(AMPK),UNC-51 like kinase 1(ULK1),Beclin1 and LC3B in decidual tissue were detected by Western blot.Results Compared with the normal group,the embryo loss rate of mice in the model group significant increased(P<0.01),the cells of the decidual tissue were disordered,the interstitium was edematous,the nuclei disappeared,there were a large number of inflammatory cells infiltration,the number of blood vessels was reduced,the contents of VEGF and VE-cadherin in decidual tissue significantly decreased(P<0.01),and the protein expressions of AMPK,ULK1,Beclin1,LC3BⅡ/LC3BⅠ significantly decreased(P<0.01).Compared with the model group,the embryo loss rate of mice in TCM high-,medium-and low-dosage groups and autophagy agonist group showed a significant downward trend(P<0.05),and the cells of decidual tissue were aligned,the interstitium edema was reduced,the nuclei of the cells increased,the inflammatory cells infiltration were reduced and the number of blood vessels increased,the contents of VEGF and VE-cadherin in decidual tissue significantly increased in TCM high-,medium-dosage groups and autophagy agonist group(P<0.05),and the protein expressions of AMPK,ULK1,Beclin1 and LC3BⅡ/LC3BⅠ significantly increased(P<0.01).Conclusion Bushen Antai Mixture may promote the recasting of blood vessels at the maternal-fetal interface by activating AMPK/ULK1/Beclin1 pathway,improve the pregnancy survival rate of RSA mice,and play a role in the treatment of RSA.