Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

ObjectiveTo explore the effects of the Tai Chi training on bone density， bone turnover markers， and heart rate variability for people with high-risk osteoporosis， and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included， and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week， and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group， and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L₁~L₄ vertebrae， bilateral femoral necks and bilateral total hips in the two groups before and after the intervention； enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention， including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide （P1NP） and β-collagen type Ⅰ cross-linking carboxy-terminal peptide （β-CTX）. Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor， they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each， and the heart rate variability （HRV） during exercise was collected， including time-domain indexes such as standard deviation of normal sinus intervals （SDNN）， root-mean-square of the difference between adjacent RR intervals （RMSSD）， frequency-domain metrics such as low-frequency power （LF）， high-frequency power （HF）， and low-frequency/high-frequency power ratio （LF/HF）， as well as nonlinear metrics such as approximate entropy （ApEn）， sample entropy （SampEn）. ResultsFinally， 63 cases were included in the outcome analysis， including 30 cases in the intervention group and 33 cases in the control group. After the intervention， the differences of L₁~L₄ vertebrae， bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention （P＞0.05）， while the bone density of all parts of the control group decreased significantly compared with that before intervention （P＜0.05）， and the difference in the bone density of the L₁~L₄ vertebrae， bilateral femoral neck， and the right total hip before and after the intervention of the intervention group was smaller than that of the control group （P＜0.05）. The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant （P＞0.05）. Compared with walking exercise， LF decreased， HF increased and LF/HF decreased during Tai Chi exercise （P＜0.05）； the time domain indexes and non-linear indexes between groups had no statistically significant difference （P＞0.05）. ConclusionTai Chi exercise can maintain lumbar， hip， and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis， but cannot significantly improve bone turnover markers.

Methods: CHB patients and healthy volunteers were enrolled from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between August 21, 2018 and December 31, 2020. They were divided into three groups: healthy group, LGDHS group, and latent syndrome (LP) group. Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify differentially expressed proteins (DEPs). Metabolomic profiling via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to serum samples to detect differentially regulated metabolites (DMs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment were employed to explore dysregulated pathways. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to visualize group separation and identify key metabolites and proteins contributing to LGDHS differentiation. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of key biomarkers, while logistic regression models assessed their predictive accuracy. P values were corrected for multiple tests using the Benjamini-Hochberg method to control the false discovery rate (FDR). Validation of potential biomarkers was conducted using independent microarray data and real-time quantitative polymerase chain reaction (RT-qPCR). Results: A total of 150 participants were enrolled, including healthy group (n = 45), LGDHS group (n = 60), and LP group (n = 45). 254 DEPs from proteomics data and 72 DMs from metabolomic profiling were identified by PCA and OPLS-DA. DEPs were mainly enriched in immune and complement pathways, while DMs involved in amino acid and energy metabolism. The integrated analysis identified seven key biomarkers: α1-acid glycoprotein (ORM1), asparagine synthetase (ASNS), solute carrier family 27 member 5 (SLC27A5), glucosidase II alpha subunit (GANAB), hexokinase 2 (HK2), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and maltase-glucoamylase (MGAM). Microarray validation confirmed the diagnostic potential of these genes, with area under the curve (AUC) values for ROC analysis ranging from 0.536 to 0.759. Among these, ORM1, ASNS, and SLC27A5 showed significant differential ability in differentiating LGDHS patients (P = 0.016, P = 0.035, and P < 0.001, respectively), with corresponding AUC of 0.749, 0.743, and 0.759, respectively. A logistic regression model incorporating these three genes demonstrated an AUC of 0.939, indicating a high discriminatory power for LGDHS. RT-qPCR further validated the differential expression of ORM1 and SLC27A5 between LGDHS and LP groups (P = 0.011 and P = 0.034, respectively), with ASNS showing a consistent trend in expression (P = 0.928). Conclusion This study integrates multi-omics approaches to uncover the molecular mechanisms underlying LGDHS in CHB. The identification of biomarkers ORM1, ASNS, and SLC27A5 offers a solid basis for the objective diagnosis of LGDHS, contributing to the standardization and modernization of TCM diagnostic practices.

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

Background::Life’s Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life’s Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life’s Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs.Methods::In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life’s Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined.Results::During the median follow-up of 10.85 years, 58, 889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however, the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%).Conclusions::Improving CVH score based on Life’s Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, avoiding overweight/obesity may be especially important to prevent new cases of metabolic diseases, NCDs in digestive system, mental and behavioral disorders, and cancer.

ObjectiveTo compare the similarities and differences of material basis for improving insulin resistance （IR） in different parts of Morus alba based on liquid-mass combination combined with network pharmacology and molecular docking technology. MethodUltra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to analyze the composition differences in different parts of M. alba. Sybyl-X2.1 was used to connect components with IR core targets， and the selection criterion was Total Score≥5. The "component-target-disease" network map was drawn. The total statistical moment standard similarity （TQSMSS） between the single target-component docking score data set and the total target-component docking score data set was calculated. The targets with higher TQSMSS were screened out， and the protein-protein interaction （PPI） network was constructed. The Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using R language. ResultForty-one active components were obtained by UPLC-Q-TOF-MS. According to the total statistical moment （similarity） method， there were 20， 23， 30， and 27 targets with TQSMSS≥0.75 in Mori Ramulus， Mori Cortex， Mori Fructus， and Mori Folium， respectively. In the four M. alba medicinal sources， the functional order of the targets by GO enrichment analysis was Mori Fructus>Mori Folium>Mori Cortex>Mori Ramulus， which were involved in biological processes such as blood glucose homeostasis， glucose metabolism， and glucose transmembrane transport. The order of the four M. alba medicinal sources by KEGG pathway enrichment analysis was Mori Fructus>Mori Ramulus>Mori Folium>Mori Cortex， which were involved in the adenosine monophosphate-activated protein kinase （AMPK） energy metabolism signaling pathway， the insulin regulation-related signaling pathway， the anti-inflammatory and anti-oxidative stress signaling pathway， and so on. ConclusionThis research demonstrates that there are differences in the material basis for improving IR by different parts of M. alba， which provides references for the development of different parts of M. alba.

Objective:To study the common pharmacodynamic substance basis and potential mechanism of Dihuang Decoction in treating Alzheimer disease (AD) and diabetes mellitus (DM) with same method based on network pharmacology; To provide bioinformatics basis.Methods:The effective components of Dihuang Decoction were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and CNKI. The drug targets were obtained by combining and UniProt database. The targets of AD and DM related diseases were obtained by GeneCards, OMIM and TTD databases respectively. Cytoscape 3.7.1 software was used to construct the Disease - drug - component - target network. R studio software was used to construct a Circos diagram of the effective compounds and disease targets.Protein-protein interaction (PPI) network was constructed using STRING platform. GO enrichment and KEGG enrichment analysis was conducted through DAVID database, Metascape, R Studio software.Results:A total of 206 active components were obtained; PPI network construction screened 51 key targets; GO enrichment analysis revealed the functions of GABA, cholinergic synapse, estrogen response, BCL-2 family protein complex and so on; KEGG enrichment analysis revealed FoxO signaling pathway, HIF-1 signaling pathway, insulin resistance pathway and other pathways.Conclusion:Dihuang Decoction has the synergistic characteristics of multiple components, multiple targets and multiple pathways in treating AD and DM with same method, mainly through proanthocyanidin B7, proanthocyanidin B5, proanthocyanidin B1 and other active ingredients, acting on TNF, IL-6, ESR1, PPARG, AKT1 and other targets, regulating FoxO signaling pathway, HIF-1 signaling pathway, etc.

Objective To analyze the prognostic factors in the patients with HER2-positive breast cancer adjuvant treated with trastuzumab.Methods We conducted a retrospective analysis of clinical data of 1 246 patients diagnosed with HER2-positive breast cancer between January 2009 and December 2019 who received treatment with trastuzumab.We investigated the factors impacting their prognosis by the Log-rank test univariate analysis and multivariate COX regression analysis.Results HER2-positive patients treated with trastuzumab had a poor prognosis in pT2-3(HR=2.10,P=0.003),pN2-3(HR=2.81,P<0.001),and no endocrine therapy(HR=2.50,P<0.001),and that had a better prognosis combined with taxane or other chemotherapy regimens(HR=0.40,P=0.017).We divided the patients into two subgroups according to the status of lymph node metastasis,and we found that in the negative lymph nodes group the patients with pT2-3 stage had poor prognosis(P=0.020),while the patients combined with taxane or other chemotherapy had better prognosis(P=0.032).In the positive lymph nodes group the patients with pT2-3 stage and no endocrine therapy had poor prognosis(P=0.012,P=0.001).Conclusions The patients with HER2-positive breast cancer treated with trastuzumab can be managed in different categories,for individuals without lymph node involvement and small tumor sizes,combining therapy with non-anthracycline chemotherapy is preferable for achieving improved outcomes,for patients with lymph node metastasis and large tumor sizes,if chemotherapy options are available,it is more recommended to use an anthracycline-free regimen to ensure the same prognosis while reducing the harm caused by the toxic side effects of chemotherapy.

OBJECTIVE: To explore the molecular mechanism of a case where RhD genotyping did not match serological results. METHODS: The serological results of 8 members from two generations of this family were analyzed. And according to Mendelian law of inheritance, RhD genotyping, zygotic type determination and gene sequencing were performed for the family members. RESULTS: The proband and one of her cousins have the same RhD alleles, both of them have a 336-1G>A intron variant RhD allele and a complete RhD deletion allele. The variant alleles are inherited from two of their parents with blood relationship, while the complete-deleted alleles come from the other. 336-1G>A means that the last base G of the second intron of the RhD gene is mutated to A, which leads to a negative RhD serology and a positive genotype in the proband. CONCLUSION There was a rare 336-1G> A intron variant gene (RhD * 01N.25) in this family, which was a recessive gene relative to the RhD gene and resulted in RhD phenotype negative.
Alleles ; Female ; Genotype ; Humans ; Introns/genetics* ; Pedigree ; Phenotype ; Rh-Hr Blood-Group System/genetics*

Objective:To clarify the evidences of hippocampal injury after radiotherapy avoiding hippocampus and explore its relationships with cognition.Methods:A prospective design was adopted in this study.A total of 183 patients with nasopharyngeal carcinoma treated by intensity modulated radiation therapy (IMRT group) and 30 matched healthy control (HC group)were collected in the Affiliated Hospital of Jiangsu University and Southeast University Affiliated Zhongda Hospital from January 2017 to December 2019. All subjects were assessed by Montreal Cognitive Assessment (MoCA-B) at baseline and 6 months after radiotherapy, then the patients with nasopharyngeal carcinoma were divided into cognitive impairment group and non-cognitive impairment group. Subjects were scanned with Siemens 3.0 T MR, and T 1WI was used as analysis sequence.The individual standardized hippocampus ROIs were extracted based on Montreal Neurological Institute(MNI) brain template.All texture features were calculated using the Radiomics developed by C++and Delphi, and the intra group correlation coefficients (ICC), average direction, machine learning (random forest) and autocorrelation matrix were used for reducing the features dimension. One-way ANOVA and generalized linear models were used to compare the differences among different groups. Pearson correlations analyses were used to evaluate the relationships between important texture features and clinical data. Logistic regressions were used to calculate the abilities of texture features to predict cognitive impairment. Results:After 9 patients who lost follow-up were excluded, a total of 164 patients with nasopharyngeal carcinoma were included as IMRT group.Texture features of ROIs were extracted and dimensionally reduced successfully. Five differences features (Variance, Entropy, GlevNonU, RLNonUni and Contrast)were found among HC group, cognitive impairment group and non-cognitive impairment group, and the last three further showed significant differences within IMRT group (GlevNonU, P=0.011;RLNonUni, P<0.001;Contrast, P<0.001). Hippocampal doses were positively correlated with Variance ( r=0.448, P<0.05), and negatively correlated with Entropy ( r=-0.461, P<0.05). There was a positive correlation between MoCA-B scores with GlevNonU, RLNonUniand Contrast ( r=0.503, P<0.05; r=0.587, P<0.05; r=0.531, P<0.05). GlevNonU and Contrast were independent predictors of cognitive impairment in hippocampal avoidance of radiotherapy (OR=0.731, 95%CI 0.610-0.857; OR=0.651, 95%CI 0.496-0.853). Conclusion:Results of texture analysis could be used as micro imaging evidences of hippocampal injury in radiotherapy avoiding hippocampus, and could also effectively predict the occurrences of cognitive impairment.