Objective:To investigate the efficacy of trimetazidine in the treatment of atrial arrhythmias in patients with ischemic cardiomyopathy and heart failure and analyze the effect of trimetazidine on cardiac function and atrial arrhythmias.Methods:A total of 79 patients with ischemic cardiomyopathy and heart failure who received treatment at the Second Hospital of Jiaxing from December 2018 to June 2020 were included in this study. These patients were randomly divided into an observation group ( n = 41) and a control group ( n = 38). Patients in the control group received conventional drugs, while those in the observation group received trimetazidine sustained-release tablets twice daily, each time taking 35 mg in addition to conventional drugs. The treatment lasted for 24 weeks. Before and after treatment, cardiac function indicators (left ventricular ejection fraction, B-type brain natriuretic peptide, 6-minute walking distance), cardiac color Doppler ultrasound indicators [ratio of early to late peak filling rate (E/A ratio)], left ventricular fractional shortening), electrocardiogram parameters (maximum P-wave duration, minimum P-wave duration, and P-wave dispersion), dynamic electrocardiogram parameters [number of single atrial premature beats, total number and duration of paroxysmal atrial tachycardia episodes, total number and duration of paroxysmal atrial flutter/fibrillation attacks, standard deviation of RR intervals, root mean square of successive differences between normal heartbeats, proportion of successive RR intervals that differ by more than 50 ms divided by the total number of NN intervals (PNN50), standard deviation of average NN intervals, high frequency and low frequency], as well as changes in high sensitivity C-reactive protein were analyzed in each group. Results:After treatment, left ventricular ejection fraction, B-type brain natriuretic peptide, 6-minute walking distance, maximum P-wave duration, P-wave dispersion, total number of atrial flutter/atrial fibrillation attacks, and duration of atrial flutter/atrial fibrillation in the observation group were (51.05 ± 7.68)%, (1 615.59 ± 1 129.78) ng/L, (350.02 ± 62.99) m, (99.73 ± 11.60) ms, (22.44 ± 12.03) ms, (0.22 ± 0.61), and (4.59 ± 12.30) minutes, respectively, which were significantly superior to (46.82 ± 7.34)%, (2 267.47 ± 1 539.03) ng/L, (294.16 ± 58.20) m, (111.71 ± 10.00) ms, (36.77 ± 15.07) ms, (0.76 ± 1.13), (15.66 ± 22.30) minutes in the control group, t = -2.95, 2.16, -4.08, 4.89, 4.68, 2.69, 2.76, all P < 0.01). Conclusion:Trimetazidine can effectively reduce atrial arrhythmias and improve the prognosis of patients with ischemic cardiomyopathy and heart failure, which warrants clinical promotion.

Objective:To explore the current situation and influencing factors of quality of life of septic patients in intensive care unit (ICU) after discharge, and to provide theoretical basis for clinical early psychological intervention and continuity of care.Methods:A prospective observational study was conducted. The septic patients who were hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University and discharged with improvement from January 1 to December 31, 2022 were selected as the research objects. The demographic information, basic diseases, infection site, vital signs at ICU admission, severity scores of the condition within 24 hours after ICU admission, various biochemical indexes, treatment process, and prognostic indexes of all the patients were recorded. All patients were assessed by questionnaire at 3 months of discharge using the 36-item short-form health survey scale (SF-36 scale), the activities of daily living scale (ADL scale), and the Montreal cognitive assessment scale (MoCA scale). Multiple linear regression was used to analyze the factors influencing the quality of life of septic patients after discharge from the hospital.Results:A total of 200 septic patients were discharged with improvement and followed up at 3 months of discharge, of which 150 completed the questionnaire. Of the 150 patients, 57 had sepsis and 93 had septic shock. The total SF-36 scale score of septic patients at 3 months of discharge was 81.4±23.0, and the scores of dimensions were, in descending order, role-emotional (83.4±23.0), mental health (82.9±23.6), bodily pain (82.8±23.3), vitality (81.6±23.2), physical function (81.4±23.5), general health (81.1±23.3), role-physical (79.5±27.0), and social function (78.8±25.2). There was no statistically significant difference in the total SF-36 scale score between the patients with sepsis and septic shock (82.6±22.0 vs. 80.7±23.6, P > 0.05). Incorporating the statistically significant indicators from linear univariate analysis into multiple linear regression analysis, and the results showed that the factors influencing the quality of life of septic patients at 3 months after discharge included ADL scale score at 3 months after discharge [ β= 0.741, 95% confidence interval (95% CI) was 0.606 to 0.791, P < 0.001], length of ICU stay ( β= -0.209, 95% CI was -0.733 to -0.208, P = 0.001), duration of mechanical ventilation ( β= 0.147, 95% CI was 0.122 to 0.978, P = 0.012), total dosage of norepinephrine ( β= -0.111, 95% CI was -0.044 to -0.002, P = 0.028), mean arterial pressure (MAP) at ICU admission ( β= -0.102, 95% CI was -0.203 to -0.007, P = 0.036) and body weight ( β= 0.097, 95% CI was 0.005 to 0.345, P = 0.044). Conclusions:The quality of life of patients with sepsis at 3 months after discharge is at a moderately high level. The influencing factors of the quality of life of patients with sepsis at 3 months after discharge include the ADL scale score at 3 months after discharge, the length of ICU stay, the duration of mechanical ventilation, the total dosage of norepinephrine, MAP at ICU admission and body weight, and healthcare professionals should enhance the treatment and care of the patients during their hospitalization based on the above influencing factors, and pay attention to early psychological intervention and continued care for such patients.

Objective The present study conducted a comprehensive literature review and visualization analysis of both domestic and international research on the utilization of hemodialysis water over the past two decades,aiming to gain insights into the current research status,identify prominent areas of interest,and highlight future development trends in this field,thereby of-fering valuable references for subsequent studies.Methods By employing bibliometric analysis,the relevant literature on hemo-dialysis water usage was retrieved from the Web of Science Core Collection(WoSCC)database and China National Knowledge Network(CNKI)for the period between 2004 and 2024.Subsequently,an in-depth examination of countries,research institu-tions,authors,and keywords associated with these publications was conducted.The visualization map was generated using CiteSpace 6.2.R4 software.Results A total of 3 304 papers were included,with 147 in Chinese and 3 157 in English.Over the past two decades,there has been a consistent upward trend in the number of publications both domestically and international-ly,although the growth rate of domestic literature lags behind that of foreign countries.The United States,China,and Japan rank as the top three countries in terms of publication volume,with the United States exhibiting the highest centrality.Foreign coun-tries tend to form small research groups with close institutional collaborations,while domestic research teams and institutions are relatively dispersed.Currently,foreign research primarily focuses on Fabrication,Ultrafiltration Membranes and Performance;meanwhile,domestic research emphasizes infection control,quality control,and daily maintenance.Conclusion From 2004 to 2024,both domestic and international researchers have consistently focused on water research for hemodialysis.However,China lags behind foreign countries in this field,necessitating enhanced collaboration among nations,institutions,and regions to broad-en the scope and depth of domestic research.

Objective To investigate the efficacy of rituximab combined with immunosuppressive pulse therapy for thyroid-associated ophthalmopathy(TAO)and analyze its influence on clinical activity score(CAS)and prognosis.Meth-ods A total of 136 patients(272 eyes)with TAO who were admitted to Huanggang Central Hospital from March 2020 to October 2022 were selected and divided into an observation group(68 patients)and a control group(68 patients)using a random number table method.Patients in the control group were given immunosuppressive pulse therapy,while patients in the observation group were given rituximab plus immunosuppressive pulse therapy.Both groups were treated for 4 courses(7 days per course).The clinical efficacy,eye signs,CAS score,thyroid conditions[thyrotropin receptor antibody(TRAb),thyroid peroxidase antibody(TPOAb),thyroid volume],T lymphocyte subsets,and adverse reactions were compared between the two groups.After a follow-up period of six months,the prognosis of patients in the two groups was compared.Results After 4 courses of treatment,the total effective rate of patients in the observation group was 94.12％(64/68),which was higher than that in the control group(82.35％,56/68)(P＜0.05).After 2 and 4 courses of treat-ment,the degree of exophthalmos,intraocular pressure,average palpebral fissure width,retrobulbar soft tissue volume,distance from the bulbus oculi,CAS score,TPOAb,TRAb,and thyroid volume of patients in the observation group were smaller than those in the control group,and all decreased compared to before treatment(all P＜0.05);the thickness of the tear film lipid layer was greater than that in the control group,and both increased compared to before treatment(all P＜0.05).There were no significant differences in the said indicators between the two groups before treatment(all P＞0.05).The CD3+,CD4+,and CD8+T lymphocyte levels of patients showed no significant difference between the two groups before treatment(all P＞0.05).After 2 and 4 courses of treatment,the levels of CD3+and CD4+T lymphocyte in both groups were higher than those before treatment.Except that the CD4+T lymphocyte level in the observation group was lower than that in the control group after 2 courses of treatment,the levels of CD3+and CD4+T lymphocyte in the obser-vation group were higher than those in the control group at other time points(all P＜0.05).After 2 and 4 courses of treat-ment,the level of CD8+T lymphocyte in both groups decreased compared to before treatment,and it was lower in the ob-servation group than the control group(all P＜0.05).There was no significant difference in the incidence of adverse reac-tions such as low fever,nausea,and hypokalemia between the two groups(all P＜0.05).After the 6-month follow-up,the improvement rate of patients in the observation group was 95.59％(65/68),which was higher than that in the control group(79.41％,54/68)(P＜0.05).Conclusion Rituximab combined with immunosuppressive pulse therapy is effec-tive for TAO.It can alleviate eye signs and thyroid conditions,reduce clinical activity,and promote prognosis.

In order to explore the genomic characteristics,its virulence,evolution,the correlation be-tween drug resistance phenotype and resistance genes of S.equi XJ 5012,to laid a theoretical basis for efficient prevention and control of strangles,whole genome sequencing was investigated.In this study,the antimicrobial suceptibility of S.equi XJ 5012 was tested by the paper disk method and its whole genome was sequenced,Then the 16S rRNA evolution,SeM genotyping,antibiotic resist-ance gene and virulence gene were compared and analyzed.Drug susceptibility results showed that S.equi XJ5012 was sensitive to 13 antibiotics,such as amoxicillin,ampicillin,cefuroxime,cefotio-fur,cefoxitin,streptomycin,erythromycin,oxytetracycline,levofloxacin,norfloxacin,ciprofloxacin,rifampicin,clindamycin,sulfadiazine sodium,and resistant to 6 antibiotics,such as penicillin,genta-micin,clarithromycin,doxycycline,tetracycline and sulfonamide isoxazole.The whole genome se-quencing results of showed that the genome size of S.equi XJ 5012 was 2.21 Mb,the GC content was 41.31％and this strain has 2 264 code genes.Antibiotic resistance genes database(ARDB)in-dicated that the S.equi XJ 5012 carried 135 drug resistance gene,among which the resistance genes mainly were macrocyclic lipids,fluoroquinolones,aminoglycosides,peptides,tetracyclines and β-lac-tam antibiotics,correlating well with the results of drug susceptibility test.Virulence Factors Data-base(VFDB)indicated that S.equi XJ 5012 carried 197 virulence genes include adhesion,antiph-agocytosis,extracellular enzyme encoding,secrtion,and iron uptake.The phylogenetic tree based on 16S rRNA gene confirmed that the strain XJ 5012 was closely related to S.equi 4047.The results of SeM genotyping revealed that S.equi XJ 5012 was SeM-217,which was closely related to Xin-jiang isolates SeM-209 and SeM-215 and foreign isolates SeM-195 and SeM-196.In this study,the whole genome sequencing analysis of S.equi XJ 5012 based on the third generation sequencing technology is the first report on the genome of S.equi in China,which provides a reference for a more comprehensive and in-depth understanding the characteristics of the genomic,molecular epi-demic and drug resistance of the strain.It is significant for the further prevention and control of strangles and understanding of pathogenic mechanism of S.equi.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Objective:To construct a nomogram model predicting the occurrence of acute kidney injury (AKI) in patients with sepsis in the intensive care unit (ICU), and to verify its validity for early prediction.Methods:Sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to December 2021 were retrospectively included, and those who met the inclusion criteria were randomly divided into training and validation sets at a ratio of 7:3. Univariate and multivariate logistic regression models were used to identify independent risk factors for AKI in patients with sepsis, and a nomogram was constructed based on the independent risk factors. Calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the nomogram model.Results:741 patients with sepsis were included in the study, 335 patients developed AKI within 7 d of ICU admission, with an AKI incidence of 45.1%. Randomization was performed in the training set ( n=519) and internal validation set ( n=222). Multivariate logistic analysis revealed that acute physiology and chronic health status score Ⅱ, sequential organ failure score, serum lactate, calcitoninogen, norepinephrine dose, urea nitrogen, and neutrophil percentage were independent factors influencing the occurrence of AKI, and a nomogram model was constructed by combining these variables. In the training set, the AUC of the nomogram model ROC was 0.875 (95% CI: 0.767-0.835), the calibration curve showed consistency between the predicted and actual probabilities, and the DCA showed a good net clinical benefit. In the internal validation set, the nomogram model had a similar predictive value for AKI (AUC=0.871, 95% CI: 0.734-0.854). Conclusions:A nomogram model constructed based on the critical care score at admission combined with inflammatory markers can be used for the early prediction of AKI in sepsis patients in the ICU. The model is helpful for clinicians early identify AKI in sepsis patients.

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

Objective:To analyze the mutation characteristics of Kirsten rat sarcoma virus oncogene homology (KRAS) gene in patients with appendiceal adenocarcinoma and its relationship with the activity of Ras Raf Mitogen activated protein kinase/extracellular regulated protein kinase (MAPK/ERK) signaling pathway.Methods:A total of 41 patients with appendiceal adenocarcinoma who were treated in the Lishui Central Hospital from January 2014 to January 2020 were selected as the observation group, and 50 patients with Appendicitis who were operated at the same time were randomly selected as the control group. Clinical and follow-up data were collected, and the mutation of the KRAS gene in the patient′s tissue was measured using the snapshot method. The expression of key proteins in the MAPK/ERK signaling pathway in cancer tissue was measured using Western blotting (WB) assay. We compared the clinical characteristics and prognosis of patients with KRAS mutation and non KRAS mutation appendiceal adenocarcinoma.Results:The KRAS gene mutation rate in the observation group was higher than that in the control group (41.5% vs 10.0%), and the expression levels of p-ARAF/ARAF, p-MEK1/MEK1, and p-ERK1/ERK1 proteins were also higher than those in the control group. The differences between the groups were statistically significant (all P<0.05). The protein expression levels of p-ARAF/ARAF, p-MEK1/MEK1, p-ERK1/ERK1 in KRAS mutation patients in the observation group were significantly higher than those in non KRAS mutation patients. The proportion of stage IV, positive rates of carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199 and CA125 in KRAS mutation patients were higher than those in non KRAS mutation patients, and the survival time and progression free survival time were shorter than those in non KRAS mutation patients, with statistical significance (all P<0.05). Conclusions:The mutation rate of KRAS in appendix adenocarcinoma is high, and the activation of MAPK/ERK signaling pathway caused by KRAS mutation may play a role in the pathogenesis of appendix adenocarcinoma, which has the value of in-depth research.

Objective:To analyze the prenatal clinical phenotypes and pregnancy outcomes of fetuses with 22q11.21 microdeletion and microduplication syndrome to provide a basis for clinical genetic counseling.Methods:This retrospective study involved the cases diagnosed with 22q11.21 microdeletion or microduplication by chromosomal microarray analysis (CMA) due to abnormal ultrasound findings, advanced maternal age, or high-risk pregnancies indicated by serum screening in the Prenatal Diagnosis Center of the First Affiliated Hospital of Air Force Medical University from January 2015 to January 2022. Clinical phenotypes and pregnancy outcomes of the fetuses were analyzed and described.Results:Among 9 141 cases referred for CMA during the study period, 77 cases (0.8%) were diagnosed as 22q11.21 microdeletion or microduplication, including 62 (80.5%) with 22q11.21 microdeletion and 15 (19.5%) with microduplication. In the 22q11.21 microdeletion cases, 58 had typical deletion, and four had atypical deletions, but all fetuses carried TBX1 gene that was clearly associated with congenital heart disease. The 15 fetuses with 22q11.21 microduplication including 14 in the typical region and one in the atypical region. Forty-eight (77.4%) out of the 62 fetuses with 22q11.21 microdeletion were complicated by congenital heart defects, including 28 with conotruncal defects. Five of the 15 fetuses with 22q11.21 microduplication were complicated by congenital heart defects. The cases were followed up on telephone at three to six months after the expected date of delivery. Among the 62 cases with 22q11.21 microdeletion, 52 terminated pregnancies, five were lost to follow-up, and five were delivered (one died after one month of premature delivery, one was born with anal advancement and growth retardation, and three were followed up without obvious abnormality). Among the 15 cases with 22q11.21 microduplication, four terminated pregnancies, two were lost to follow-up, and nine gave birth (eight were followed up without obvious abnormality, one grew slowly). Conclusions:The application of CMA in the prenatal diagnosis of 22q11.21 microdeletion and microduplication fetuses, and the comprehensive analysis of clinical manifestations and pregnancy outcome combined with ultrasonic diagnosis are of great significance in guiding the treatment and rehabilitation after birth of an affected child. Genetic counseling for cases with 22q11.21 microdeletion and microduplication syndrome should be cautious and consider ultrasound findings.