ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Objective: Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure. Methods: Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue. Results: Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05). Conclusion Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.

Intestinal pathogenic bacteria utilize their own virulence factors to interfere with the nor-mal function of intestinal epithelial cells and evade clearance by the host immune system through precise gene regulation and expression strategies,thereby causing a variety of diseases.It has been found that the mechanisms affecting the gene expression strategies of pathogens include the toxin-antitoxin system,secretory system,and quorum sensing system.Novel antimicrobial strategies are being developed to interfere with the inherent gene regulatory system of bacteria and inhibit the expression of virulence genes,thus enabling a modest approach to the treatment of intestinal disea-ses.This paper initially discusses the components of innate immunity in the gut,followed by a dis-cussion of the common gene regulatory system of intestinal pathogenic bacteria.This article aims to clarify the mechanisms by which intestinal pathogenic bacteria evade clearance by the innate im-mune system through gene regulation and expression strategies,and to provide new ideas for the treatment of intestinal bacterial diseases.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To investigate the bacterial isolate distribution and differences of antimicrobial resistance among community-acquired infection，healthcare-associated infection and hospital-acquired infection.Methods:Bacterial isolates from clinical specimens were collected in Xi'an No.1 Hospital between January 2019 and December 2023 and categorized into community-acquired infection（CAI），healthcare-associated infection（HCAI）and hospital-acquired infection（HAI）. The bacterial distribution and antimicrobial resistance differences among the three groups were compared. Data were analyzed with SPSS 22.0 statistical software.Results:A total of 9 762 bacterial strains were collected：2 258 strains（23.1%）in CAI group，763 strains（7.8%）in HCAI group and 6 741 strains（69.1%）in HAI group. In HCAI group，the detection rate of Escherichia coli was lower than that in CAI group，and higher than that in HAI group（ χ2=106.335 and 69.603，both P<0.001）. The detection rates of Pseudomonas aeruginosa and Acinetobacter baumannii in HCAI group were higher than those in CAI group（ χ2=35.749 and 65.098，both P<0.001），and lower than those in HAI group（ χ2=26.350 and 115.885，both P<0.001）. The detection rate of Staphylococcus aureus in HCAI group was higher than that in CAI and HAI groups（ χ2=5.745 and 13.992，both P<0.05）. In HCAI group，the detection rate of methicillin-resistant Staphylococcus aureus（MRSA）was lower than that in HAI group（ χ2=69.005， P<0.001）；and MRSA in HCAI demonstrated higher resistance to levofloxacin and moxifloxacin than that in CAI group（ χ2=13.634 and 13.083，both P<0.001），and lower than that in HAI group（ χ2=17.927 and 21.937，both P<0.001）. The resistance rates of Escherichia coli to piperacillin/tazobactam，ceftriaxone，ceftazidime，cefoperazone/sulbactam，ciprofloxacin and levofloxacin in HCAI group were higher than those in CAI group，and the resistance rates to cefoperazone/sulbactam，meropenem，imipenem and amikacin in HCAI group were lower than those in HAI group（all P<0.05）. For Klebsiella pneumoniae，the resistance rate in HCAI group was higher than that in CAI group and lower than that in HAI group to all antibacterial agents，except for nitrofurantoin（all P<0.01）. For Pseudomonas aeruginosa，the resistance rate in HCAI group was higher than that in CAI group（ χ2=14.107，14.819，16.822 and 15.998，all P<0.001）and lower than that in HAI group（ χ2=7.821，4.671，18.070 and 17.552，all P<0.05）to piperacillin/tazobactam，cefoperazone/sulbactam，meropenem and imipenem. Acinetobacter baumannii in HCAI group demonstrated lower resistance to piperacillin/tazobactam，meropenem，imipenem，ciprofloxacin and levofloxacin than that in HAI group（ χ2=32.263，31.526，42.417，25.277 and 6.798，all P<0.01）. Conclusion:The bacterial distribution and antimicrobial resistance in HCAI group are different from CAI and HAI groups. It is recommended to carry out precise antibiotic resistance surveillance in different categories of infections for rational antibiotic use.

Objective:To investigate the efficacy of color Doppler ultrasound-guided percutaneous nephrostomy in the treatment of anastomotic leakage after laparoscopic pyeloplasty.Methods:A retrospective analysis was performed for the data of 15 children with peritoneal irritation after LP who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to January 2023, of which 10 cases were anastomotic leaks and 5 cases were with renal pelvic blood clots. There were 12 males and 3 females. Age (4.2±2.7) years. The lesions were located on the left side of 11 cases and on the right side of 4 cases. All 15 cases had varying degrees of nausea, vomiting, abdominal pain and other symptoms. Physical examination: the children all showed painful faces and tense abdominal muscles. 15 patients had a preoperative pain score of 9.5 (8, 10). Ultrasound examination showed that the anterior and posterior diameters of renal pelvis separation were (34.93±4.86) mm, the anterior and posterior diameter/renal parenchymal thickness of renal pelvis separation was 15.66±1.02, renal dynamic nuclear imaging shows the renal function of the affected side was (29.69±1.71)%. Thirteen cases had the above symptoms before the abdominal drainage tube was removed, and the time of symptom onset was (3.3±1.1) days after surgery, of which 8 cases had a large increase in abdominal drainage, and color Doppler ultrasonography showed a large amount of fluid in the intra-abdominal intestinal space (about 500 ml). In 5 cases, the intraperitoneal drainage volume did not increase, and color Doppler ultrasonography showed strong echo in the renal pelvis, and blood clots were considered. All 13 patients were placed in the prone position under local anesthesia and underwent color Doppler ultrasound-guided percutaneous nephrostomy. The remaining 2 cases had abdominal drainage tube removed on the 3rd day after surgery, and peritoneal irritation signs appeared on the 4th and 6th days after surgery, respectively. Color Doppler ultrasonography showed that there was a large amount of fluid in the intra-abdominal intestinal space, and color Doppler ultrasound-guided peritoneal puncture and drainage + prone percutaneous nephrostomy was performed in the supine position under local anesthesia, and the biochemical analysis of the peritoneal puncture drainage fluid was confirmed to be anastomotic urine leakage. The drainage volume and urine output of 15 cases of peritoneal puncture drainage and pyelostomy were recorded, and the relief of nausea and vomiting symptoms and the score of postoperative pain after percutaneous nephrostomy were recorded. The changes of hydronephrosis and renal function before and after percutaneous nephrostomy were compared.Results:In this study, 15 patients underwent percutaneous nephrostomy with a duration of (16.8±1.9) min. The symptoms of nausea and vomiting disappeared after operation, and the pain scores were 3.2(2, 4) and 0.4(0, 2) at 2 h and 12 h after operation, respectively, which were statistically significant compared with those before operation ( P<0.01). In 13 children with simple percutaneous nephrostomy, the abdominal drainage tube was removed on (3.6±0.8) days and (8.6±1.0) days after percutaneous nephrostomy. In 2 children with peritoneal puncture and drainage plus percutaneous nephrostomy, the abdominal drainage tube was removed 3 days after the fistula operation, and the pyelostomy tube was removed 8 days after the fistula operation. The anterior and posterior diameters of renal pelvis separation were (10.87±4.05), (10.13±3.50) and (9.13±3.11) mm by color Doppler ultrasound at 3, 6 and 12 months after LP operation, respectively, and there were statistically significant differences compared with preoperative comparisons ( P<0.01).The diameter before and after renal pelvis separation was (7.60±2.86) mm, the diameter before and after renal pelvic separation/renal parenchymal thickness was 1.97±0.22, and the renal function was (39.23±2.66)% at 24 months after operation, which was statistically significant compared with that before operation ( P<0.01). Conclusions:Color Doppler ultrasound-guided percutaneous nephrostomy can effectively alleviate symptoms in the early stage, which could help to the healing of ureteral anastomosis, and has less trauma and short operation course.

Objective:To explore the effect of pentraxin 3 (PTX3) on memory improvement and Aβ expression in Alzheimer's disease (AD) model mice.Methods:(1) Ten 5-month-old 5×FAD mice were randomly divided into PTX3 group and model group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 group and control group were stereotactically injected 4 μL 0.5 g/L PTX3 or same dose of phosphate buffered saline (PBS); Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the brain hemisphere. (2) Twenty-five 3-month-old 5×FAD mice were randomly divided into model group, 2 μg/kg PTX3 group, 4 μg/kg PTX3 group, 8 μg/kg PTX3 group, and 16 μg/kg PTX3 group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 groups were intranasally injected 2, 4, 8, and 16 μg/kg PTX3, respectively; those in the model group and control group were intranasally injected same dose of PBS; injection was given once every 96 h for a total of 7 times. Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the hippocampus. Results:(1) Compared with the model group, the PTX3 group had significantly shorter platform latency, higher percentage of exploration time and higher percentage of spontaneous alternations ( P<0.05). Compared with those in model group ([63.38±21.42] pg/mL, [29.77±6.11] pg/mL), the concentrations of Aβ 40 and Aβ 42 in the brain tissues of PTX3 group ([15.87±2.11] pg/mL, [16.55±1.95] pg/mL) were statistically lower ( P<0.05). (2) Compared with the model group, the 16 μg/kg PTX3 group had significantly shorter escape latency and higher percentage of exploration time ( P<0.05); compared with the model group, the 2 μg/kg PTX3 group and 16 μg/kg PTX3 group had significantly higher percentage of spontaneous alternations ( P<0.05). The contents of Aβ 40 and Aβ 42 in the hippocampus of 8 μg/kg PTX3 group and 16 μg/kg PTX3 group were statistically lower compared with those in the model group ( P<0.05). Conclusion:PTX3 may attenuate cognitive deficits and decrease Aβ expression in the brain or hippocampus tissues of 5×FAD mice with AD.

Objective:To analyze the clinical characteristics and risk factors of acute kidney injury (AKI) in portal venous hypertension patients undergoing transjugular intrahepatic portosystemic shunt (TIPS).Methods:It was a retrospective observational study. In this study, the clinical data of portal venous hypertension patients undergoing TIPS at Beijing Shijitan Hospital, Capital Medical University from October 16, 2020 to March 30, 2022 were collected retrospectively. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI, patients were divided into AKI group and non-AKI group. The clinical characteristics of the patients were compared between the two groups, and multivariate logistic regression was used to analyze the risk factors of AKI.Results:A total of 384 patients undergoing TIPS were included in this study, whose age was (53.17±13.35) years. Among them, 122 (31.8%) were female, and 32 patients (8.3%) had AKI. Compared to the non-AKI group, the proportion of patients with diabetes mellitus, baseline estimated glomerular filtration rate (eGFR) <60 ml·min -1·(1.73 m 2) -1 and intraoperative hypotension, Child-Pugh score of liver function, preoperative serum creatinine, preoperative blood uric acid, and postoperative portal venous pressure gradient (PPG) were higher in AKI group (all P<0.05), while the levels of hemoglobin and serum albumin were lower (both P<0.05). Multivariate logistic regression results showed that combined diabetes ( OR=3.728, 95% CI 1.262-11.013, P=0.017), baseline eGFR<60 ml·min -1·(1.73 m 2) -1( OR=3.571, 95% CI 1.356-9.400, P=0.010), decreased serum albumin ( OR=0.847, 95% CI 0.738-0.972, P=0.018), increased PPG after TIPS ( OR=1.096, 95% CI 1.002-1.200, P=0.045) and intraoperative hypotension ( OR=7.006, 95% CI 2.023-24.195, P=0.002) were independently associated with postoperative AKI in portal venous hypertension patients undergoing TIPS. Until discharge, 6 patients with AKI (18.8%) had complete renal function recovery, 24 patients (75.0%) partially recovered, and 2 patients (6.3%) did not recover. The length of hospital stay, hospitalization costs, and all-cause mortality in AKI patients were significantly higher than those in the non-AKI group ( P<0.05, respectively). Conclusions:AKI is not uncommon in patients receiving TIPS. The classical risk factors of AKI, such as diabetes and baseline renal dysfunction, and the factors affecting volumes like lower serum albumin level, hypotension during the operation, and higher PPG level are closely related to the incidence of AKI in these patients. AKI significantly increases the all-cause mortality and medical expenses, which is worth early prevention and treatment by clinicians.

Objective:To investigate the changes and associated factors of cerebral blood flow in middle-aged and elderly patients undergoing maintenance hemodialysis (MHD).Methods:This was a prospective observational study. End-stage renal disease (ESRD) patients undergoing MHD aged over 50 years at Beijing Shijitan Hospital, Capital Medical University from January 2023 to June 2023 were included. General clinical data of the selected individuals were collected, and dialysis related indicators were recorded and calculated. Mean flow velocity (MFV) of the middle cerebral arterial was measured by transcranial Doppler sonography (TCD) to represent cerebral blood flow throughout dialysis. Hemodialysis-related variables were collected. The MFV values of bilateral middle cerebral artery were measured through temporal windows at 7 time points: 15 minutes before dialysis (T1), 15 minutes (T2), 30 minutes (T3), 60 minutes (T4), 120 minutes (T5), 180 minutes (T6) during dialysis, and the endpoint of dialysis (T7), and the average values were recorded. The ΔMFV was calculated as pre-minus endpoint values of MFV. The Spearman rank correlation method was used to analyze the correlations between ΔMFV and dialysis-related variables, and multiple linear regression method was used to analyze the related factors of the changes in MFV.Results:This study included a total of 123 patients undergoing MHD, aged (63.63±8.44) years (range 50-85 years), including 99 males (80.5%). TCD examination demonstrated a decline trend in MFV throughout dialysis. The MFV at T7 was significantly lower than that at T1 ( Z=-7.650, P<0.001). The Spearman correlation analysis showed that the decline in MFV was correlated with ultrafiltration volume ( r=0.356), ultrafiltration rate ( r=0.371), the difference in systolic pressure (pre-analysis minus post-dialysis, r=0.251), the difference in mean arterial pressure (pre-dialysis minus post-dialysis, r=0.194), combined diabetes ( r=0.293), dialysis vintage ( r=0.220), Kt/V ( r=0.287), and serum albumin ( r=-0.295). Multiple linear regression analysis showed that combined with diabetes ( B=3.889, 95% CI 1.373-6.405, P=0.003), decreased serum albumin ( B=-0.456, 95% CI -0.877--0.036, P=0.034), increased ultrafiltration rate ( B=11.099, 95% CI 6.402-15.797, P<0.001) and the decline in systolic pressure ( B=0.062, 95% CI 0.008-0.116, P=0.026) were significantly associated with the decline in MFV throughout dialysis. Conclusions:In middle and elderly patients with ESRD undergoing hemodialysis, there is a decline trend in cerebral blood flow during hemodialysis. The combination of diabetes, lower serum albumin, higher ultrafiltration rate, and intradialytic systolic pressure decline are the risk factors influencing the intradialytic decline of cerebral blood flow.

Objective To investigate the mechanism of Yiqi Tongmai Powder(Ginseng Radix et Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Hirudo,Eupolyphaga Steleophaga,Rhei Radix et Rhizoma)against cerebral ischemia-reperfusion injury(CIRI)based on network pharmacology,molecular docking and experimental verification.Methods(1)The active components of Yiqi Tongmai Powder and their action targets were screened by TCMSP,TCMID and ETCM databases,the disease related targets of CIRI were screened by GeneCards,OMIM and TTD disease databases,and the intersection targets of the above targets were obtained through Venny 2.1 online platform,that is,the potential targets of Yiqi Tongmai Powder in the treatment of CIRI.The"drugs-active components-targets"network was constructed by Cytoscape 3.7.1 software,and the potential active components of Yiqi Tongmai Powder in the treatment of CIRI were screened.Protein-protein interaction(PPI)analysis of potential targets was carried out by STRING 11.0 database to screen core targets.The GO function and KEGG pathway enrichment of potential targets were analyzed by Metascape database.AutoDockTools 1.5.7 software was used to verify the molecular docking between the key active components and the core targets.(2)The rat model of CIRI was established by middle cerebral artery occlusion and reperfusion(MCAO/R).SD rats were randomly divided into sham operation group,model group,Yiqi Tongmai Powder low-dose group(0.27 g·kg-1),Yiqi Tongmai Powder high-dose group(1.08 g·kg-1)and Nimodipine group(30 mg·kg-1),with 10 rats in each group.Pre-administration began three days before the establishment of the model,once a day for seven days.The neurological deficit of MCAO/R rats was evaluated by modified neurological deficit score(mNSS).The volume of cerebral infarction was measured by TTC staining.Nissl staining was used to observe the damage of neurons in brain tissue.ELISA method was used to detect serum inflammatory factors and oxidative stress related indexes.TUNEL staining was used to detect brain tissue apoptosis.Western Blot method was used to detect the protein expressions of Bax and Bcl-2 in brain tissue.Results(1)A total of 46 active components and 178 potential targets of Yiqi Tongmai Powder in the treatment of CIRI were obtained.The key active components such as quercetin,digitalis flavonoids,kaempferol,valine and uracil were analyzed,and the core targets such as TNF,IL-6,STAT3,VEGFA,AKT1,IL-1β,CASP3,TP53,MAPK3 and EGFR were analyzed.The potential targets are involved in inflammation,oxidative stress,cell proliferation and differentiation,apoptosis and other biological processes,including cAMP,NF-κB,PI3K-Akt and other signal pathways.The main active components quercetin,flavonoids of digitalis,kaempferol and valine have good binding activity to target proteins such as TNF,IL-6,STAT3 and VEGFA.(2)Compared with the model group,the neurological deficit score of rats in each treatment group was significantly decreased(P＜0.05,P＜0.01),the area of cerebral infarction was significantly decreased(P＜0.01),and the pathological changes of ischemic necrotic area of brain tissue were improved.The number of neurons in ischemic area of brain tissue was significantly increased(P＜0.01),and the rate of neuronal apoptosis was significantly decreased(P＜0.01).The levels of serum IL-1β,IL-6,TNF-α and MDA were significantly decreased,while the activities of SOD and GSH-Px were significantly increased(P＜0.05).The protein expression of Bax in brain tissue were significantly decreased and the protein expression of Bcl-2 significantly increased(P＜0.05).Conclusion Yiqi Tongmai Powder may play an anti-CIRI effect by reducing inflammation and oxidative stress,inhibiting cell apoptosis.