Objective:Integrating genes and GEO database related cuproptosis chips,to analyze connection between cupropto-sis genes,immune infiltration and myocardial infarction(MI),construct risk prediction model,predict Western medicine and Chi-nese medicine,analyze miRNA-mRNA regulatory network,and to provides a new research direction for the future study of MI-related cuproptosis mechanism and immune infiltration.Methods:By GEO database retrieval of MI related chips,standardized processing and MI-related cuproptosis genes screening were performed,and immunoinfiltration analysis and quantification were performed based on the treated gene expression matrix,correlation between immune infiltrating cells and function was analyzed,as well as their differ-ences in MI group and the control group.Cuproptosis genes that most related to MI in immune infiltration were screened out,and the risk model was constructed to analyze the risk probability of cuproptosis genes in MI.The Enrichr website and Coremine Medical data-base were used to predict cuproptosis-related genes in MI in Western medicine and traditional Chinese medicine.Finally,the up-stream mirnas of FDX1 and SLC31A1 were predicted by miRTarBase,Starbase and Targetscan databases,and miRNA-mRNA regula-tory networks were constructed.Results:Correlation of immune infiltration showed that Tfh cells and B cells had the strongest positive correlation(r=0.68),while regulatory T cells and iDC had the strongest negative correlation(r=-0.63);the difference analysis of im-mune infiltration showed that the differences among mast cells,NK cells and Th1 cells in the MI group at the cellular level were the most significant(P<0.001);and the differences in APC co-inhibition and MHCⅠ at the functional level were the most significant(P<0.001).Six genes with the highest correlation between immune cells and immune function were screened out:ATP7A,DLD,FDX1,LIAS,LIPT1 and SLC31A1.Results of the risk model showed that the high levels of FDX1 and SLC31A1 were negatively correlated with the risk prediction of MI.A total of 21 Western medicines and 30 traditional medicines were predicted by database comparison.miRTarBase,Starbase and Targetscan databases predicted 9 upstream miRNAs of cuproptosis-related genes in MI,including has-miR-122-5p.Conclusion:Tfh cells,B cells,para-inflammatory,typeⅠinterferon response and other related immune cells and functions may play important roles in pathogenesis and prognosis of MI.FDX1 and SLC31A1 as the key genes of cuproptosis process,are negatively correlated with MI.A total of 30 kinds of traditional Chinese medicines including Spirulina,sheep liver,Wen ezhu,Pian jianghuang and Yujin may have potential value in treatment of MI.Finally,9 miRNAs including has-miR-122-5p may play an important role in the regulation of cuproptosis in myocardial infarction.

Objective To investigate the effect and mechanism of Liraglutide on the spatial learning and memory function in type 2 diabetes mellitus(T2DM)rats.Methods SD rats were randomly divided into control group(NC),T2DM group(T2DM)and Liraglutide group(Lir).The ability of learning and memory was evaluated by Morris water maze method.Apoptosis of hippocampal neuron was tested by TUNEL staining.The mRNA expression levels of inflammatory cytokines TNF-α,IL-1β and IL-6 were measured by real time-PCR.The protein expressions of heme oxygenase-1(HO-1),NADPH oxidase 1(NOX1),protein B-cell lymphoma-2(Bcl-2)and Bcl2-associated X(Bax)in hippocampus tissues were determined by Western blot.Results Compared with T2DM group,the percent time in target quadrant was increased in Lir group(P<0.05),while the escape latency of day 3 to day 5 was significantly decreased in Lir group(P<0.05).The apoptosis of hippocampal neurons was reduced in Lir group,and the morphological changes,including hyperchromatic cytoplasm and karyopyknosis were alleviated.Compared with T2DM group,MDA content,mRNA level of TNF-α,IL-1β and IL-6,and protein expression of NOX1 and Bax were decreased(P<0.05),while T-AOC,SOD,HO-1 and Bcl-2 protein expression were increased in Lir group(P<0.05).Conclusions Liraglutide ameliorates diabetes-related learning and memory impairment by regulating antioxidant,anti-inflammatory and anti-apoptotic effects in hippocampus.

OBJECTIVE: To compare the clinical efficacy between staged acupuncture based on "thoroughfare vessel is the sea of blood" theory combined with routine hormone replacement cycle treatment and routine hormone replacement cycle treatment for patients with recurrent implantation failure (RIF) of thin endometrium. METHODS: A total of 72 RIF patients with thin endometrium were randomly divided into an observation group and a control group, 36 cases in each group. The patients in the control group were treated with routine hormone replacement cycle treatment. Based on the treatment of the control group, the patients in the observation group were treated with staged acupuncture based on "thoroughfare vessel is the sea of blood" theory. The main acupoints were Neiguan (PC 6) and Gongsun (SP 4), and the supplementary acupoints were selected according to the menstrual cycle and syndrome differentiation; the acupuncture was given once every other day, 3 times a week, for 3 consecutive menstrual cycles. The thickness and shape of endometrium, and Hamilton anxiety scale (HAMA) score were observed at implantation window before and after treatment; the clinical pregnancy rate, live birth rate and cycle cancellation rate were compared between the two groups; the correlation between endometrial thickness and HAMA score was analyzed. RESULTS: Compared before treatment, the endometrial thickness in the two groups and the proportion of type A+B endometrium in the observation group were increased (P<0.05), and the HAMA scores in the two groups were decreased (P<0.05) after treatment. The above indexes in the observation group were superior to those in the control group (P<0.05). The clinical pregnancy rate and live birth rate in the observation group were higher than those in the control group (P<0.05), and the cycle cancellation rate was lower than that in the control group (P<0.05). There was a negative correlation between endometrial thickness and HAMA score (P<0.05). CONCLUSION Based on the routine hormone replacement cycle treatment, the addition use of staged acupuncture based on "thoroughfare vessel is the sea of blood" theory could improve the thickness and shape of endometrium, relieve anxiety, increase the clinical pregnancy rate and live birth rate, and reduce the cycle cancellation rate in RIF patients with thin endometrium. The curative effect is superior to the routine hormone replacement cycle treatment alone.
Female ; Pregnancy ; Humans ; Anxiety ; Anxiety Disorders ; Acupuncture Therapy ; Endometrium ; Hormones

Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD). The etiology and pathogenesis of DGE have not been fully elucidated in China and globally, and the majority of patients can be cured after general symptomatic treatment. This article reviews the risk factors and pathophysiological mechanisms of DGE after PD, in order to provide a reference for the effective management of DGE after PD in clinical practice.

Aim To investigate the mechanism through which liraglutide (LRG) inhibited high glucose (HG)-induced cardiomyocyte hypertrophy. Methods Cultured H9c2 were divided into control (CON) group, HG group, low-, middle- and high-dose LRG (LRG-L, LRG-M and LRG-H) groups, LRG-H + autophagy inhibitor trimethyladenine (3-MA) group. The relative cell surface change was assessed phalloidin staining. Membrane bound Na, K

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R²_pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Objective:To evaluate the right atrial volume and function abnormalities in patients with pulmonary hypertension (PH) by four-dimensional automatic quantitation technique, and to explore the application value of this technique in evaluating the risk stratification and World Health Organization functional class(WHO-FC) of PH patients.Methods:Eighty-four adult patients with PH diagnosed by right heart catheterization from April to October 2022 in Fuwai Central China Cardiovascular Hospital were consecutively enrolled as the PH group. All cases were divided into 3 groups according to the mean pulmonary arterial pressure (mPAP): mild PH group ( n=28), moderate PH group ( n=28), severe PH group ( n=28). Twenty-eight healthy volunteers matched by gender and age were included in the same period as the control group. The volume and strain parameters of the right atrium were obtained by analyzing the four-dimensional image of the right atrium using four-dimensional automatic quantitation technique, including right atrial minimum volume index (RAVImin), right atrial maximum volume index (RAVImax), right atrial presystolic volume index (RAVIpreA), right atrial ejection fraction (RAEF), right atrial passive ejection fraction (RAPEF), right atrial active ejection fraction, RAAEF, longitudinal strains of right atrial reserve, conduit and systolic period (RASr, RAScd, RASct), circumferential strains of right atrial reserve, conduit and systolic period (RASr-c, RAScd-c, RASct-c). The differences in right atrial parameters among four groups were compared.ROC curve was used to analyze the diagnostic efficiency of right atrial four-dimensional strain parameters for PH patients with WHO-FC≥Ⅲ. Pearson linear correlation analysis was used to investigate the relationships between RASr and right atrial area (RAA), NT-proBNP and tricuspid annular plane systolic excursion to pulmonary arterial systolic pressure ratio (TAPSE/sPAP). Results:①Compared with the control group, RAEF, RAPEF, RASr, RAScd, RASr-c, RAScd-c were significantly decreased in mild, moderate and severe PH groups; while RAAEF, RASct, RASct-c were significantly increased in mild PH group and significantly decreased in moderate and severe PH groups, and the differences were statistically significant (all P<0.05). RAVImin, RAVImax, RAVIpreA gradually increased among the control, mild PH, moderate PH and severe PH groups, and the differences were statistically significant (all P<0.05). RAEF, RAPEF, RAAEF, RASr, RAScd, RASct, RASr-c, RAScd-c, RASct-c were decreased successively among mild, moderate and severe PH groups, and the differences were statistically significant (all P<0.05). ②ROC curve showed that RASr had the highest diagnostic efficiency in PH patients with WHO-FC ≥Ⅲ, and the cut-off value was 20.5% (AUC=0.914, P<0.001). ③Correlation analysis showed that RASr was correlated with RAA, NT-proBNP and TAPSE/sPAP ( r=-0.803, -0.621, 0.739; all P<0.001). Conclusions:The degree of right atrial function impairment increased in patients with mild, moderate and severe PH in turn. RASr is the best predictor of WHO-FC ≥Ⅲ in patients with pulmonary hypertension and is a potential parameter for risk stratification in patients with PH.