ObjectiveTo investigate the mechanism of the modified of Bazhentang combined with Guishentang in improving pregnancy outcomes in mouse models of embryo implantation dysfunction by regulating T helper 1/T helper 2 （Th1/Th2） immune balance. MethodsEighty ICR female mice were randomly divided into four groups （n=20 per group） on gestational day 1 （GD1）： control， model， western medicine， and traditional Chinese medicine （TCM） groups. Except for the control group， all mice received mifepristone solution （0.2 mg/mouse） via oral gavage on GD4 to induce embryo implantation dysfunction. The TCM group received a water decoction of the modified of Bazhentang combined with Guishentang （20.8 g·kg^-1）， with the western medicine group administered dydrogesterone （3.9 mg·kg^-1）， and the control/model groups given equal volumes of saline. All treatments were administered once daily from GD1 until one day before sample collection. Outcomes included implantation site counts （macroscopic observation）， pregnancy rates， body weight， endometrial histopathology （hematoxylin-eosin staining）， uterine expression of T-box expressed in T cells （T-bet）， GATA-binding protein 3 （GATA3）， interferon gamma （IFN-γ）， and interleukin-4 （IL-4） at protein （Western blot） and mRNA （real-time polymerase chain reaction， Real-time PCR） levels， serum IFN-γ and IL-4 levels （enzyme-linked immunosorbent assay， ELISA）， and Th1/Th2 immune balance evaluated by calculating T-bet/GATA3 and IFN-γ/IL-4 ratios. ResultsCompared to the control group， the model group showed no significant change in pregnancy rate but exhibited a marked reduction in average implantation sites and body weight （P<0.01）. Histopathological analysis revealed endometrial abnormalities， including decreased glandular density， stromal compaction， and absence of nucleolar vacuoles. At the molecular level， uterine tissue in the model group demonstrated significantly upregulated expression of T-bet and IFN-γ （P<0.05， P<0.01）， alongside markedly downregulated GATA3 and IL-4 expression （P<0.05， P<0.01）. Serum analysis confirmed markedly elevated IFN-γ （P<0.01） and reduced IL-4 levels （P<0.01）， resulting in significantly increased T-bet/GATA3 and IFN-γ/IL-4 ratios （P<0.01）. Compared to the model group， pregnancy rates in all treatment groups showed no significant change. Implantation sites and body weight increased substantially （P<0.01）， with restored endometrial morphology characterized by enhanced glandular density， stromal edema， and reappearance of nucleolar vacuoles. Significant downregulation of T-bet and IFN-γ （P<0.01） and upregulation of GATA3 and IL-4 （P<0.05， P<0.01） in uterine tissue were observed. Serum IFN-γ levels were significantly reduced （P<0.05， P<0.01）， while IL-4 levels were significantly elevated （P<0.05）. The Th1/Th2 ratios were significantly decreased （P<0.01）. ConclusionThe modified of Bazhentang combined with Guishentang significantly enhances the number of embryo implantation sites in mice with embryo implantation dysfunction， potentially through modulating T-bet/GATA3 expression， restoring Th1/Th2 immune balance， and improving endometrial receptivity.

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.

Objective:To investigate the effects of Wumei-Fangfeng drug on Treg/Th17 immune balance in allergic rhinitis(AR)mice via regulating MMP9 derived from mast cell exosomes.Methods:Potential targets of Wumei and Fangfeng were screened,and the intersection was taken from the targets and AR risk genes,subsequently GO analysis and protein-protein interaction analysis were performed to screen therapeutic targets.AR mice model were constructed,mast cells and exosomes were separate from femurs of mice.Wumei-Fangfeng drug and exosomes were used to treat mice.The behavioral scores of mice in each group were evaluated,mRNA expressions of Foxp3,RORγt were detected in nasal mucosa of mice.After knocking down of MMP9 in exosomes,the behavioral score,Foxp3 and RORγt mRNA expressions were observed in AR mice.Results:Bioinformatics results showed that Wumei-Fangfeng drug may act on AR by mast cell exosomes derived IL-1β and MMP9.Compared with normal mice,mRNA expression of Foxp3 in AR mice was decreased,while RORγt mRNA expression was increased,and MMP9 expression was increased(all P<0.05).Expression of Foxp3 mRNA was increased,and expressions of RORγt and MMP9 were decreased in AR mice treated with Wumei-Fangfeng drug,however,mast cell exosomes could further counteract the effects of Wumei-Fangfeng drug,and the effects of mast cell exosomes was weakened after MMP9 knockdown.Conclusion:Wumei-Fangfeng drug regulates the imbalance of Treg/Th17 in AR mice by inhibiting the exosomal MMP9 of bone marrow-derived mast cells.

Objectives:Distolingual root of the permanent mandibular first molar(PMFM-DLR)has been frequently reported,which may complicate the treatment of periodontitis.This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background.Materials and methods:A total of 836 cone beam computed tomography(CBCT)images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China.Among them,complete periodontal charts were available for 69 Chinese patients with 103 teeth.Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR,bone loss,and periodontal clinical parameters,including clinical attachment loss(CAL),probing pocket depth(PPD),gingival recession(GR),and furcation involvement(FI).Results:The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4%and 26.3%,respectively.Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section,while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section.Conclusions:The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort.The morphological features of DLR were correlated with the periodontal status of mandibular first molars.This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

The guidelines for curriculum ideological and political of nursing ethics explored the ideological and political elements of Chinese nursing,and proposed the curriculum's ideological and political goals.The development framework and basic ideas of guidelines were formed from the aspects of the integration path of curriculum ideological and political,and professional teaching,searching for the entry point of curriculum ideological and political,reforming the teaching methodology,enriching the form of teaching,and constructing the case base of curriculum ideological and political.It promoted the deep integration of nursing professional knowledge transmission and ideological value guidance,created a distinctive education system of curriculum ideological and political for nursing ethics,and provided a reference for the curriculum ideological and political construction of national nursing ethics.

As the most commonly used antipyretic and analgesic drug,paracetamol(PA)coexists with neuro-transmitter dopamine(DA)in real biological samples.Their simultaneous determination is extremely important for human health,but they also interfere with each other.In order to improve the conductivity,adsorption affinity,sensitivity,and selectivity of TiO2-based electrochemical sensor,N-doped carbon@-TiO2 double-shelled hollow sphere(H-C/N@TiO2)is designed and synthesized by simple alcoholic and hydrothermal method,using polystyrene sphere(PS)as a template.Meanwhile,TiO2 hollow spheres(H-TiO2)or N-doped carbon hollow spheres(H-C/N)are also prepared by the same method.H-C/N@TiO2 has good conductivity,charge separation,and the highly enhanced and stable current responses for the detection of PA and DA.The detection limit and linear range are 50.0 nmol/L and 0.3-50 μmol/L for PA,40.0 nmol/L and 0.3-50 μmol/L for DA,respectively,which are better than those of carbon-based sen-sors.Moreover,this electrochemical sensor,with high selectivity,strong anti-interference,high reli-ability,and long time durability,can be used for the simultaneous detection of PA and DA in human blood serum and saliva.The high electrochemical performance of H-C/N@TiO2 is attributed to the multi-functional combination of different layers,because of good conductivity,absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO2.

Objective:To dynamically monitor the prevalence and trend of dental fluorosis in children in Shandong Province, and to evaluate the prevention and control measures for drinking water-borne endemic fluorosis (referred to as drinking water-borne fluorosis), and to provide scientific basis for the next step.Methods:Totally 40 counties (cities, districts) were selected as project counties (cities, districts) from drinking water-borne fluorosis areas in Shandong Province in 2018, and all counties (cities, districts) were selected in 2019 and 2020, to investigate the situation of water improvement, detect water fluoride content, and investigate the prevalence of dental fluorosis in children aged 8 - 12 years.Results:From 2018 to 2020, the detection rates of dental fluorosis in children aged 8 - 12 years were 10.30% (503/4 884), 8.94% (25 895/289 539) and 8.66% (24 061/277 689), respectively, with statistically significant differences (χ 2 = 27.10, P < 0.001), and the dental fluorosis indexes were 0.21, 0.18 and 0.17, respectively. The total detection rates of dental fluorosis in children of different age groups in the 3 years were 7.26% (6 590/90 775), 7.97% (9 303/116 680), 9.29% (12 167/130 915), 9.29% (12 238/131 670) and 9.95% (10 161/102 072), the differences were statistically significant (χ 2 = 615.71, P < 0.001). In the 3 years, the total detection rate of dental fluorosis was 8.93% (28 101/314 737) in boys and 8.69% (22 358/257 375) in girls, the difference was statistically significant (χ 2 = 10.27, P = 0.001). In 2018 and 2019, the detection rates of dental fluorosis of children aged 8 - 12 years in water fluoride qualified villages [5.74% (235/4 095) and 7.98% (20 200/253 082)] were significantly lower than those in villages with excessive water fluoride [33.97% (268/789) and 15.62% (5 695/36 457), χ 2 = 570.61, 2 283.76, P < 0.001]. Conclusions:The prevalence of dental fluorosis among children aged 8 - 12 years has been effectively controlled, and remarkable results have been achieved in prevention and treatment of drinking water-borne fluorosis in Shandong Province. However, the detection rate of dental fluorosis among children in a few endemic villages is high, so it is necessary to continue to strengthen the monitoring of fluoride content in drinking water and the condition of dental fluorosis among children.

Accurate detection of low frequency mutations from plasma cell-free DNA in blood using targeted next generation sequencing technology has shown promising benefits in clinical settings. Duplex sequencing technology is the most commonly used approach in liquid biopsies. Unique molecular identifiers are attached to each double-stranded DNA template, followed by production of low-error consensus sequences to detect low frequency variants. However, high sequencing costs have hindered application of this approach in clinical practice. Here, we have developed an improved duplex sequencing approach called SinoDuplex, which utilizes a pool of adapters containing pre-defined barcode sequences to generate far fewer barcode combinations than with random sequences, and implemented a novel computational analysis algorithm to generate duplex consensus sequences more precisely. SinoDuplex increased the output of duplex sequencing technology, making it more cost-effective. We evaluated our approach using reference standard samples and cell-free DNA samples from lung cancer patients. Our results showed that SinoDuplex has high sensitivity and specificity in detecting very low allele frequency mutations. The source code for SinoDuplex is freely available at https://github.com/SinOncology/sinoduplex.

Objective:To investigate the effect of guided imagery relaxation therapy on pain self-efficacy and quality of life in patients with gynecological malignant tumor.Methods:A total of 94 gynecological malignant tumor patients were assigned to study group and control group by random digits table method with 47 cases each, the control group received routine nursing, while the study group carried out guided imagery relaxation therapy for 4 weeks. The pain degree, pain self-efficacy and quality of life was assessed by Chinese version of Brief Pain Inventory (BPI-C), Chronic Pain Self-efficacy Scale (CPSS) and Quality of Life Questionnaire-core 30 (QLQ-C30), before and 4-week after intervention.Results:Compared to the control group, the scores of pain right now, pain at worst in the 24 hours, pain on the average of BPI-C and symptom scales, single items of QLQ-C30 were (3.76±0.54), (4.37±1.39), (3.63±0.73), (32.40±8.69), (34.34±5.81) points in the study group, and (4.18±0.93), (5.18±1.75), (4.23±0.97), (37.72±6.37), (38.54±6.84) points in the control group, the differences were statistically significant( t values were 2.415-3.287, all P <0.05). The scores of self-efficacy for pain management, self-efficacy for physical function, self-efficacy for coping with symptoms, total CPSS total scale and function scales, global QOL scale were (17.43±5.50), (27.25±4.40), (29.76±6.46), (74.44±9.21), (72.73±17.74), (64.02±11.03) points in the study group, and (14.68±3.53), (22.60±4.01), (24.87±4.03), (62.14±7.10), (65.60±13.89), (57.23±15.60) points in the control group, the differences were statistically significant( t values were 2.105-7.036, P <0.05 or 0.01). Conclusions:Guided imagery relaxation therapy can alleviate cancerous pain and promote pain self-efficacy and quality of life of patients with gynecological malignant tumor.

Objective:To explore the correlation between preoperative serum hyaluronic acid (HA) level and prognosis of breast cancer patients.Methods:The 98 patients with breast cancer who underwent surgical treatment in the Oncology Department of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2004 to November 2014 in a historical cohort were included, aged (52.5±9.4) years.The preoperative serum HA contents of the patients were detected. According to the median of 53.7 μg/L, the patients were divided into high and low groups with 49 patients in each group.The χ 2 test was used to analyze the correlation between the serum HA content and the general clinical data of the patients, and the Kaplan-Meier method, Log-rank test and multivariate Cox regression model wereusedto analyze the correlation between HA content and patients′ survival. Results:The percentages of patients with high HA levels in menopause and non-menopause patientswere 55.7% and 40.5%, respectively; in progesterone receptor (PR) positive and negative patients were 54.1% and 43.2%, respectively; in estrogen receptor (ER) positive and negative patients were 45.7% and 60.7%, respectively; in Ki-67 positive and negative patients were 55.6% and 43.2%, respectively; in the tumor size stage TⅠ, TⅡ, TⅢ, and TⅣ patients were 50.0%, 41.7%, 72.7%, and 1/1, respectively; in lymph node metastasis and non-metastasispatients were 45.7% and 53.8%, respectively. There was no significant correlation between the level of HA and the menopausal status, the expressions of PR, ER and Ki-67, tumor size, and lymph node metastasis in breast cancer patients (χ2=2.128, 1.086, 1.800, 1.485, 4.273, 0.656, P>0.05). Patients with high HA levels accounted for 30.9% of patients aged 52 years or less and 74.4% of patients older than 52 years (χ2=18.274, P=0.000); 43.4% of patients with early TNM and 72.7% of patients with advanced TNM (χ2=5.861, P=0.015); 45.2% of patients without distant metastasis and 78.6% of patients with distant metastasis (χ2=5.333, P=0.023); 38.1% of Her-2 negative patients and 58.9% of Her-2 positive patients(χ2=4.167, P=0.041); and the median survival of patients with high HA levels was 70 months, which was shorter than 83 months for patients with low HA levels (χ2=6.799, P=0.007). Therefore, ahigh HA content predicts an older age, a later tumor stage, higher risk of distant metastasis, positive expression of Her-2 and shorter survival. Multivariate Cox regression model analysis suggested that high levels of serum HA may be a risk factor for patients′ survival, with HR (95% CI) value of 9.98 (1.16-85.88) and P value of 0.036. Conclusion:The high level of preoperative serum HA has a certain correlation with the poor prognosis of breast cancer patients.