Objective To investigate the factors influencing international normalized ratio (INR)>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Methods A retrospective analysis was performed on the clinical data of patients who underwent mechanical heart valve replacement surgery and received warfarin anticoagulation therapy at West China Hospital of Sichuan University from January 1, 2011 to June 30, 2022. Based on the discharge INR values, patients were divided into two groups: an INR≤3.0 group and an INR>3.0 group. The factors associated with INR>3.0 at the time of discharge were analyzed. Results A total of 8901 patients were enrolled, including 3409 males and 5492 females, with a median age of 49.3 (43.5, 55.6) years. The gender, body mass index (BMI), New York Heart Association (NYHA) cardiac function grading, INR, glutamic oxaloacetic transaminase, and preoperative prothrombin time (PT) were statistically different between the two groups (P<0.05). Multivariate logistic regression analysis revealed that lower BMI, preoperative PT>15 s, and mitral valve replacement were independent risk factors for INR>3.0 at discharge (P<0.05). Conclusion BMI, preoperative PT, and surgical site are factors influencing INR>3.0 at discharge in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Special attention should be given to patients with lower BMI, longer preoperative PT, and mitral valve replacement to avoid excessive anticoagulation therapy.

BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective:To assess the goal fulfillment in terms of blood glucose, blood pressure, blood lipid, and the composite indicator of these three in patients with diabetes who received intensified treatment at Peking Union Medical College Hospital and regular follow-up for 12 months, analyze the influencing factors, and explore the comprehensive management model for intensive diabetes treatment outpatient services.Methods:This study was a prospective, observational cohort study. The diabetes patients who received long-term regular follow-up at the intensive diabetes treatment outpatient clinic of Peking Union Medical College Hospital from 2012 to 2023 were selected as the research subjects. They were followed up and clinical data were collected at the 1st, 3rd, 6th, 9th, and 12th months of follow-up. The study assessed the goal fulfillment rates in terms of blood glucose, blood pressure, blood lipid, and the composite indicator of these three, with the goals of glycated hemoglobin (HbA1c)<7%, blood pressure<130/80 mmHg, and low-density lipoprotein cholesterol (LDL-C)<2.6 mmol/L. The study also analyzed the impact of factors, including gender, age, type of diabetes, duration of diabetes, body mass index, comorbidities, complications, and treatment regimens, on the outcomes of comprehensive diabetes management.Results:A total of 232 patients were included in the study, of whom 210 were with type 2 diabetes (90.5%), 13 with type 1 diabetes (5.6%), 5 with latent autoimmune diabetes of the adult (2.2%), 3 with diabetes after total pancreatectomy (1.3%), and 1 with mitochondrial diabetes (0.4%). After 3 months of intensified management, the goal fulfillment rates of blood glucose (67.7% vs. 34.1%, Kappa=0.336, P<0.001), blood pressure (53.4% vs. 37.5%, Kappa=0.159, P=0.001), blood lipid (59.1% vs. 39.2%, Kappa=0.198, P<0.001), and the composite indicator (20.7% vs. 3.0%, Kappa=0.177, P<0.001) were significantly increased. Continued treatment at 6, 9, and 12 months showed stable and sustained increases in the goal fulfillment rates of blood glucose, blood pressure, blood lipid, and the composite indicator. Logistic regression analysis showed that baseline hyperglycemia ( P=0.002), disease duration ≥5 years ( P<0.001), smoking ( P=0.009), alcohol consumption ( P=0.038), presence of diabetic complications ( P=0.001), combination therapy with oral antidiabetic drugs and insulin ( P<0.001), and use of antiplatelet drugs ( P=0.037) were risk factors for uncontrolled HbA1c. Baseline hypertension ( P<0.001), alcohol consumption ( P=0.030), and comorbid dyslipidemia ( P=0.028) were risk factors for uncontrolled blood pressure. Baseline uncontrolled LDL-C ( P=0.020) and non-use of statins ( P<0.001) were risk factors for uncontrolled blood lipid. Conclusions:Among patients with the long-term follow-up at our intensive diabetes treatment clinic, the goal fulfillment rates of blood glucose, blood lipid, blood pressure, and the composite indicator of these three are relatively higher. However, it is still necessary to improve patient compliance as much as possible, emphasize weight management, and persist on the comprehensive diabetes treatment.

AIM To explore the laws in accumulation of dry matter and medicinal ingredients of Isatis indigotica Fort.in Longdong area,and determine the best harvest time to obtain the high-quality and high-yield medicinal plant.METHODS The I.indigotica had its agronomic traits investigated regularly;the accumulation laws of its uridine,guanosine,(R,S)-geichan and adenosine measured by HPLC;and its comprehensive utilization value in different periods evaluated by grey correlation method.RESULTS There existed significant variations among the plant height,plant width,leaf length,leaf width,number of leaves,leaf weight,root length,root diameter,root weight,and the yields of uridine,guanosine,(R,S)-goitrin and adenosine at different growth stages,whose peak values appeared in different period.Additionally,there were also obvious differences in the aforementioned indexes levels among different strains.The highest weighted correlation degree of the comprehensive utilization value of Longde and 2008-6-2 on October 9,and of 2008-11 and 2016-2 on October 24.On the whole,the 2008-6-2 and 2016-2 were superior to 2008-11 and Longde.CONCLUSION It is suggested that the best harvest time of I.indigotica in Longdong area is in mid to late October.

Objective:To study the distribution of TCM constitutions in maintenance hemodialysis (MHD) patients.Methods:This is a multicenter cross-sectional study. The general clinical data, dialysis-related parameters and physical and chemical examination data of MHD patients from 6 dialysis centers in Sichuan were collected. At the same time, DS01-A tongue and facial pulse information collection system was used for TCM constitution discrimination.Results:A total of 232 MHD patients were enrolled , and 417 kinds of TCM constitutions were detected, including 59 patients (25.43%) with moderate constitution and 173 patients (74.57%) with biased constitution. Phlegm-dampness was the most common type of solid constitution 47 patients (20.26%). The most common deficiency constitution was qi deficiency 86 patients (37.07%). There were certain differences in the physical distribution of patients with different gender, age, dialysis age, BMI, and whether they had diabetes, hypertension or anemia.Conclusions:The TCM constitutions of MHD patients are mainly biased constitution. Gender, age, BMI, diabetes or hypertension have a certain impact on the distribution of TCM constitutions. At the same time, different constitutions may have an impact on the anemia of MHD patients. The intervention of TCM constitutions on MHD patients may be beneficial to the prognosis of MHD patients.

In order to provide basic information for the utilization and development of famous classical formulas containing Bletillae Rhizoma， this article systematically analyzes the historical evolution of the name， origin， harvesting and processing of Bletillae Rhizoma by reviewing the ancient materia medica， prescription books， medical books and modern literature. The research results showed that Baiji（白及） was the main name， some scholars took Baiji（白芨） as its main name， and there were many other names such as Baiji（白给）， Baigen（白根）， Baiji（白苙）. The mainstream source of Bletillae Rhizoma was the tubers of Bletilla striata， and drying， large， white， solid， root-free and skin removed completely were the good quality standards. With the promotion of wild to cultivated medicinal materials， there were certain differences between their traits， and the quality evaluation indexes should be adjusted accordingly. The origin of records in the past dynasties was widely distributed， with Guizhou and Sichuan having high production and good quality in modern times. The harvesting period is mostly in spring and autumn， and harvested in autumn was better. The processing and processing technology is relatively simple， and it was used fresh or powdered in past dynasties， while it is mainly sliced for raw use in modern times. Based on the results， it is suggested that the tubers of Bletilla striata of Orchidaceae should be used in the famous classical formulas， and it should be uniformly written as Baiji（白及）. And if the original formula indicates the requirement of processing， it should be operated according to the requirement， if the requirement of processing is not indicated， it can be used in raw form as medicine.

Objective:To realize the optimization and upgradation of the detection method of you only look once(YOLO)algorithm model based on the improved YOLO network on the ultrasound image for breast tumor.Methods:A total of 659 images of breast tumor of the Kaggle database were selected as the initially dataset,and the image annotation tool Labelimg was used to conduct pre-labeling for the detection targets in the images.According to a ratio as 7:3,629 images of the 659 images were divided into the train set and validation set,and the other 30 images were used as the test set.The convolutional block attention module(CBAM)and bidirectional feature pyramid network(BiFPN)were introduced into the original YOLO algorithm to underwent structural improvement,which was named as YOLOv5-BiFPN-CBAM.Both the train set and validation set were placed in original YOLO algorithm model and YOLOv5-BiFPN-CBAM model to conduct train,which included 200 rounds of iterative training.The obtained optimal weight files were used in the final test of test set.Results:After 200 rounds of iterative train for two kinds of models,the test results of validation set indicated that the mean values of average precision of two kinds of models were respectively 72.1%and 80.5%for all ultrasound images of breast tumor.The result,that the optimal weight file of improved model was tested by test set,indicated the test ability of improved model was significantly enhanced than that of original model for small target in image.Conclusion:Compared with the original YOLO algorithm model,the improved YOLO algorithm model has higher recognition capability for image,which also enhances precision and sensitivity in identifying small targets of ultrasound images of breast tumor.This model is helpful to improve the diagnostic efficiency in clinical practice for breast tumor.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.