Objective To analyze differentially expressed proteins(DEPs)in the hippocampal tissue of an amyloid-beta 1-42(Aβ1-42)-induced Alzheimer's disease(AD)rat model using Tandem mass tag(TMT)-based quantitative proteomics,followed by bioinformatic analysis to explore potential AD mechanisms.Methods Twelve male Sprague-Dawley(SD)rats were randomly assigned to a control group(n=6)and a model group(n=6).The AD model was established by bilateral hippocampal injection of Aβ1-42 in the model group,while the control group received an equivalent volume of saline.Cognitive function was assessed using the novel object recognition test,and hippocampal Aβ deposition was detected by immunofluorescence.DEPs were identified using TMT-based proteomics and subsequently analyzed via Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interaction(PPI)network analysis.Key DEPs were validated using parallel reaction monitoring(PRM)technology.Results The model group exhibited a significantly lower novel object recognition index(P<0.01)and significantly increased hippocampal Aβ deposition(P<0.01)compared to the control group.Proteomic analysis identified 183 DEPs(87 upregulated,96 downregulated).GO analysis revealed that DEPs were primarily enriched in processes such as amyloid-beta binding and ion transmembrane transport.KEGG analysis indicated significant enrichment in 42 pathways,including dopaminergic synapse,glutamatergic synapse,cholinergic synapse,and long-term potentiation.Ten core DEPs were identified from the PPI network,and PRM validation confirmed expression trends consistent with the TMT results.Conclusion Aβ1-42-induced AD involves the synergistic action of multiple targets,biological processes,and pathways.The activation of glutamatergic and dopaminergic synaptic signaling pathways,mediated by core DEPs(e.g.,Th、D1、VGLUT2、GluN2A、GluA1、GluA3、Shank1、DARPP-32、PKC-δ、PKC-α、PKA C-β、CaMKⅡα、PTK2B),likely represents a key molecular mechanism in this AD model,providing a basis for identifying potential therapeutic targets.

Tegoprazan is a novel potassium-competitive acid blocker with long-lasting and potent acid-suppressing effects,showing favorable efficacy in many acid-related diseases.In eradicating Helicobacter pylori(Hp)infections,tegoprazan-based regimens are noninferior to proton pump inhibitor(PPI)regimens in terms of efficacy,and are well tolerated and safe.In this article,we review the pharmacological mechanism,clinical studies on Hp eradication regimens,and safety of tegoprazan to provide a reference for the selection of Hp e-radication regimens.

Objective To analyze differentially expressed proteins(DEPs)in the hippocampal tissue of an amyloid-beta 1-42(Aβ1-42)-induced Alzheimer's disease(AD)rat model using Tandem mass tag(TMT)-based quantitative proteomics,followed by bioinformatic analysis to explore potential AD mechanisms.Methods Twelve male Sprague-Dawley(SD)rats were randomly assigned to a control group(n=6)and a model group(n=6).The AD model was established by bilateral hippocampal injection of Aβ1-42 in the model group,while the control group received an equivalent volume of saline.Cognitive function was assessed using the novel object recognition test,and hippocampal Aβ deposition was detected by immunofluorescence.DEPs were identified using TMT-based proteomics and subsequently analyzed via Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interaction(PPI)network analysis.Key DEPs were validated using parallel reaction monitoring(PRM)technology.Results The model group exhibited a significantly lower novel object recognition index(P<0.01)and significantly increased hippocampal Aβ deposition(P<0.01)compared to the control group.Proteomic analysis identified 183 DEPs(87 upregulated,96 downregulated).GO analysis revealed that DEPs were primarily enriched in processes such as amyloid-beta binding and ion transmembrane transport.KEGG analysis indicated significant enrichment in 42 pathways,including dopaminergic synapse,glutamatergic synapse,cholinergic synapse,and long-term potentiation.Ten core DEPs were identified from the PPI network,and PRM validation confirmed expression trends consistent with the TMT results.Conclusion Aβ1-42-induced AD involves the synergistic action of multiple targets,biological processes,and pathways.The activation of glutamatergic and dopaminergic synaptic signaling pathways,mediated by core DEPs(e.g.,Th、D1、VGLUT2、GluN2A、GluA1、GluA3、Shank1、DARPP-32、PKC-δ、PKC-α、PKA C-β、CaMKⅡα、PTK2B),likely represents a key molecular mechanism in this AD model,providing a basis for identifying potential therapeutic targets.

Objective To observe the effects of electroacupuncture on the learning and memory abilities of Alzheimer disease(AD)rats;To explore its potential mechanism based on proteomics.Methods Totally 36 SD male rats were randomly divided into sham-operation group,model group and heart meridian acupoints group,with 12 rats in each group.Aβ1-42 were injected into the bilateral hippocampus to establish AD rat model,the sham-operation group was injected with an equal volume of normal saline.The heart meridian acupoints group received electroacupuncture treatment,accompanied by a stimulation time of 20 minutes,rest for 1 day after 6 days of electroacupuncture for 7 consecutive weeks.The Morris water maze experiment was used to evaluate the learning and memory abilities of AD rats,tandem mass tag(TMT)labeling technology and bioinformatics analysis were used to screen core differentially expressed proteins in important typical pathways,and key differentially expressed protein was verified by parallel reaction monitoring(PRM).Results There was no statistically significant difference in swimming speed between each group of rats(P>0.05).Compared with the sham-operation group,the escape latency of Morris water maze experiment in the model group increased significantly(P<0.01);compared with the model group,the escape latency of heart meridian acupoints group was significantly shortened on the 2-4th day(P<0.01).A total of 209 differentially expressed proteins were identified in different groups using TMT labeling quantification,among which 12 proteins showed significant changes among the 3 groups.GO annotation involved biological processes such as metal ion transport,sodium ion transport,and sodium ion transmembrane transport,as well as cellular components such as synapses,presynapse,and synaptic vesicle,involving solute:sodium symporter activity,organic acid:sodium symporter activity,amino acid:cation symporter activity,amino acid:sodium symporter activity,and other molecular functions;KEGG analysis significantly enriched the synaptic vesicle pathway.The PRM validation results indicated that electroacupuncture at the heart meridian acupoints could reduce the expressions of sodium and chloride dependent GABA transporter protein 3(GAT3),which was consistent with the quantitative detection results of TMT labeling quantification.Conclusion Electroacupuncture at the heart meridian acupoints can improve the learning and memory abilities of AD rats,possibly by regulating the expression of synaptic transporter GAT3 on the synaptic vesicle pathway to exert neuroprotective effects.

Objective::Computed tomography pulmonary angiography (CTPA) parameters are valuable for predicting pulmonary hypertension (PH) in patients with pulmonary embolism (PE). However, few studies have used the coronary sinus ostium area (CSOA), derived from CTPA, to detect PH. This study aimed to compare the prognostic values of the CSOA, coronary sinus ostium diameter (CSOD), and right ventricular (RV)/left ventricular (LV) ratio for PH.Methods::This study retrospectively analyzed 78 patients (mean age, (51.94 ± 12.33) years; 53.8% male) with acute PE confirmed by CTPA at the Sixth and Eighth Medical Centers of the People’s Liberation Army General Hospital between June 2018 and June 2020. Patients were categorized into 2 groups using a pulmonary artery systolic pressure (PASP) cut-off of 30 mmHg. CTPA parameters were compared between these groups.Results::Patients with PASP >30 mmHg ( n = 22) had a larger CSOA, CSOD, RV diameter, RV/LV ratio, and inferior vena cava diameter compared with patients with PASP ≤30 mmHg ( n = 56). The CSOA had an area under the receiver-operating characteristic curve (AUC, 0.84; 95% confidence interval (CI), 0.74-0.94; P < 0.001) similar to that of the RV/LV ratio (AUC, 0.85; 95%CI, 0.73-0.99; P < 0.001), while that of the CSOD was smaller (AUC, 0.66; 95%CI, 0.51-0.81; P < 0.05). Conclusion::Both CSOA and CSOD demonstrated a good ability to predict PH, while CSOA better predicted PASP >30 mmHg.

Objective::Computed tomography pulmonary angiography (CTPA) parameters are valuable for predicting pulmonary hypertension (PH) in patients with pulmonary embolism (PE). However, few studies have used the coronary sinus ostium area (CSOA), derived from CTPA, to detect PH. This study aimed to compare the prognostic values of the CSOA, coronary sinus ostium diameter (CSOD), and right ventricular (RV)/left ventricular (LV) ratio for PH.Methods::This study retrospectively analyzed 78 patients (mean age, (51.94 ± 12.33) years; 53.8% male) with acute PE confirmed by CTPA at the Sixth and Eighth Medical Centers of the People’s Liberation Army General Hospital between June 2018 and June 2020. Patients were categorized into 2 groups using a pulmonary artery systolic pressure (PASP) cut-off of 30 mmHg. CTPA parameters were compared between these groups.Results::Patients with PASP >30 mmHg ( n = 22) had a larger CSOA, CSOD, RV diameter, RV/LV ratio, and inferior vena cava diameter compared with patients with PASP ≤30 mmHg ( n = 56). The CSOA had an area under the receiver-operating characteristic curve (AUC, 0.84; 95% confidence interval (CI), 0.74-0.94; P < 0.001) similar to that of the RV/LV ratio (AUC, 0.85; 95%CI, 0.73-0.99; P < 0.001), while that of the CSOD was smaller (AUC, 0.66; 95%CI, 0.51-0.81; P < 0.05). Conclusion::Both CSOA and CSOD demonstrated a good ability to predict PH, while CSOA better predicted PASP >30 mmHg.

Objective:To build a simple, rapid and accurate visual prediction model for identifying the ST-segment elevation myocardial infarction (STEMI) patients with high risk of no reflow during the primary percutaneous coronary intervention (PPCI).Methods:A retrospective study of STEMI patients treated by PPCI in China-Japan Friendship Hospital from January 2018 to June 2019 was performed. The clinical data including sex, age, comorbidities, personal history, Killip classification and laboratory examinations were collected. Whether the patients had no reflow during the PPCI were retrospective observed. Multivariable logistic regression analysis was used to identify risk factors. A nomogram was developed to predict no reflow risk among STEMI patients. C-index and Hosmer-Lemeshow goodness-of-fit test were used to verify the differentiation, consistency and clinical applicability of the model. Internal verification of the model was used by Bootstrap validation.Results:Of the included 280 patients, the prevalence of no flow rate was 30.7%. Killip class Ⅲ or Ⅳ ( OR=3.537, 95% CI: 1.665-7.514, P=0.002), mean platelet volume≥9 fL ( OR=4.003, 95% CI: 1.091-14.689, P=0.037), Glucose ≥7.8 mmol/L ( OR=2.315, 95% CI: 1.318-4.066, P=0.003) and time from symptoms to hospital ( OR=5.594, 95% CI: 2.041-15.328, P=0.002) were the independent risk factors of no flow (all P<0.05). The AUC of ROC curve in the prediction model was 0.731 (95% CI: 0.668-0.795). The calibration curves were close to the standard curve. Conclusions:The visual prediction model constructed in this study can early identify STEMI patients with high risk of no reflow, and may be helpful for physicians to provide prospective pre-treatment before the occurrence of no reflow during PPCI.

Objective:To evaluate the accuracy of serum concentration of procalcitonin (PCT) in differential diagnosis of the etiology of bloodstream infections (BSI).Methods:Patients hospitalized in ICU of China-Japan Friendship Hospital from January 2015 to June 2020 with BSI and with PCT test simultaneously when blood drawing for blood culture were enrolled. Sequential Organ Failure Assessment (SOFA) were calculated based on parameters on the day of blood culture. Difference of various indicators among different pathogen infections were compared. Receiver Operating Characteristic (ROC) Curve was used to analyze the value of PCT in differential diagnosis of BSI by different pathogens.Results:Among 1 456 patients with BSI,1 261 (86.6%) patients with monobacterial infection, 80 (5.5%) patients with candidiasis and 115 (7.9%) patients with mixed infection. The 28-day mortality was 24.5% (356/1 456) and the 60-day mortality was 30.6% (446/1456). Mortality of both 28-day and 60-day in the mixed group was significantly higher than that in the bacteriacemia group and candidemia group. PCT levels was significantly higher in patients with bacteremia caused by gram-negative bacteria (GNB) than that in gram-positive bacteria (GPB) infected bacteremia and candidemia {3.4 μg/L[95% confidence interval (95% CI) 0.7-17.0 μg/L] vs 1.3 μg/L (95% CI 0.4-7.3 μg/L); 3.4μg/L (95% CI was 0.7-17.0 μg/L) vs 1.1 μg/L (95% CI was 0.4-3.4 μg/L); P<0.01} . ROC curve analysis showed that: ① the optimal cut-off value of PCT in differential diagnosis of monobacterial bacteremia and candidemia was 7.25 μg/L, with specificity of 90.0% and the area under the ROC curve (AUROC) was 0.612 (95% CI 0.533-0.691). When PCT value was greater than 0.51 μg/L, the sensitivity of diagnostic of bacteremia could reach 73.3%. ② the optimal cut-off value of PCT in differential diagnosis of bacteremia caused by GNB infection and candidemia was 7.32 μg/L, with specificity of 90.0% and AUROC was 0.695 (95% CI 0.614-0.776). When PCT value was greater than 0.51 μg/L, the sensitivity of diagnostic of bacteremia caused by GNB infection was 84.9%.③ the optimal cut-off value of PCT in differential diagnosis of bacteremia caused by GNB and GPB infection was 0.52 μg/L, with sensitivity of 84.9% and AUROC was 0.713 (95% CI 0.672-0.755). When PCT value was greater than 7.36 μg/L, the specificity of diagnostic of bacteremia caused by GNB infection could reach 80.1%. Conclusions:PCT can provide additional information about the possible etiology of patients with BSI, especially as high levels often indicate the possibility of GNB bacteremia.

Objective:To compare the early and late predictive values of critical illness score (CIS) and procalcitonin (PCT) in septic patients with blood stream infection (BSI) induced by intra-abdominal infection (IAI), and to identify the value of PCT in etiological diagnosis.Methods:The clinical data of patients with at least one positive blood culture within 24 hours admission to the emergency department of China-Japan Friendship Hospital from January 2014 to December 2019 and with final diagnosis of IAI induced sepsis were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) scores were calculated based on the parameters on the day of admission. Differences in various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28 days or 60 days were compared. Receiver operator characteristic curve (ROC curve) was used to analyze the value of PCT in differential etiological diagnosis of IAI induced sepsis caused by single bacterial infection, and the predictive value of CIS and PCT on 28-day and 60-day death of septic patients with BSI induced by IAI.Results:A total of 221 septic patients with IAI caused by single bacterial infection were enrolled. The 28-day mortality was 19.9% (44/221), and the 60-day mortality was 25.8% (57/221). Mortality caused by Gram-positive (G +) bacterial infection of patients was significantly higher than that caused by Gram-negative (G -) bacterial infection (28 days: 34.6% vs. 11.4%, 60 days: 42.0% vs. 16.4%, both P < 0.01). Compared with patients with G + bacterial infection, the PCT value of patients with G - bacterial infection was higher [μg/L: 4.31 (0.71, 25.71) vs. 1.29 (0.32, 10.83), P < 0.05]. Compared with survival group, the values of CIS and PCT in death group were higher, either in 28 days or in 60 days [death group vs. survival group in 28 days: SOFA score was 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 11 (9, 14) vs. 6 (6, 9), LODS score: 4.0 (2.0, 6.0) vs. 1.0 (0, 2.0), APACHEⅡ score: 17.0 (15.0, 24.0) vs. 12.0 (8.0, 15.0), PCT (μg/L): 3.48 (1.01, 26.70) vs. 2.45 (0.32, 15.65); death group vs. survival group in 60 days: SOFA score: 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 9 (6, 14) vs. 6 (6, 9), LODS score: 4.0 (1.0, 5.0) vs. 1.0 (0, 2.0), APACHEⅡ score: 16.5 (12.0, 20.0) vs. 12.0 (8.0, 15.0), PCT (μg/L): 2.67 (0.98, 17.73) vs. 2.22 (0.31, 16.75); all P < 0.05]. ROC curve showed that: ① the area under ROC curve (AUC) of PCT in the diagnosis of IAI induced sepsis with single bacterial infection was 0.740 [95% confidence interval (95% CI) was 0.648-0.833]. When the optimal cut-off value of PCT was 1.82 μg/L, the sensitivity of diagnosis of G - bacterial infection was 74.0%, and the specificity was 68.2%. When PCT value was higher than 10.92 μg/L, the specificity of diagnosis of G - bacterial infection could reach 81.8%. ② In the prediction of 28-day and 60-day mortality for septic patients with BSI induced by IAI, the APACHEⅡ score achieved the highest AUC [28 days: 0.791 (95% CI was 0.680-0.902), 60 days: 0.748 (95% CI was 0.645-0.851)]. APACHEⅡ score higher than 14.5 could help to predict 28-day and 60-day mortality for IAI patients with negative predictive values of 94.9% and 88.5%. However, the predictive value of PCT for septic patients with BSI induced by IAI was relatively lower [28-day AUC: 0.610 (95% CI was 0.495-0.725), 60-day AUC: 0.558 (95% CI was 0.450-0.667)]. Conclusion:PCT is more reliable in the identification of pathogen type among IAI induced sepsis with BSI, while APACHEⅡ score may perform better in predicting early and late mortality.

Objective: To investigate the application value of real-time virtual sonography(RVS)in the diagnosis and treatment of complicated hepatolithiasis. Methods: The retrospective and descriptive study was conducted. The clinical data of 10 patients with complicated hepatolithiasis who were admitted to Hunan Provincial People′s Hospital between October 2017 and March 2018 were collected. There were 3 males and 7 females, aged from 40 to 69 years, with an average age of 57 years. Patients received abdominal color Doppler ultrasound examination, magnetic resonance cholangiopancreatography, and upper abdominal spiral computed tomography (CT) thinly scanning + enhanced examination. Data of CT examination were imported into RVS. RVS was used to locate hepatolithiasis, relationship between stones and vessels, anatomy of bile ducts and vessels in hepatic hilus. Surgical methods included RVS-guided hilar cholangiotomy, biliary stricturoplasty, bilateral hepatojejunostomy, hepatic segmentectomy (lobectomy), and hepatolithotomy. Observation indicators: (1) surgical and postoperative situations; (2) typical case analysis; (3) follow-up. Follow-up using outpatient examination was performed to detect residual stones up to June 2019. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results: (1) Surgical and postoperative situations: 10 patients underwent RVS-guided surgeries successfully for complicated hepatolithiasis, with successful match in RVS (difference between CT images and ultrosound images <2 mm). No residual stone was identified by choledochoscope during operation. The operation time and volume of intraoperative blood loss were 285 minutes (range, 210-360 minutes) and 200 mL (range, 100-600 mL), respectively. No blood transfusion was needed during the operations. The duration of hospital stay was 20.5 days (range, 14.0-29.0 days). There was no perioperative death. One patient had postoperative biliary leakage and abdominal infection, and was cured after conservative treatment. (2) Typical case analysis: the tenth patient, female, 60 years old, was diagnosed with complicated hepatolithiasis, and was prepared to undergo hepatolithotomy+ quadrate lobectomy and hilar cholangioplasty+ bilateral hepatojejunostomy. Preoperative CT images and intraoperative color Doppler ultrasound images of the patient were fused and matched on the sagittal section of the portal vein and the cross section of the right branch of portal vein, and stones and important vessels were marked on the images. After accurate positioning, a curette was used to remove the stones. Removal of biliary stones through hepatic parenchyma and peripheral dilated bile ducts was conducted at the site where stones obviously existed. After the stones were removed, the intrahepatic bile duct and hilar bile duct merged. The left end of the bile duct split was confirmed by real-time ultrasound. After location of portal vein was determined by ultrasound, vascular plastic surgery was perfomed to avoid stenosis. (3) Follow-up: 10 patients were followed up for 6-12 months, with a median follow-up time of 8 months. One of 10 patients was suspected residual stones at the right peripheral hepatic anterior lobe by postoperative angiography at 2 months after surgery, and was not removed stones by choledochoscope. The patient had no recurrent symptoms after T-tube removal. The other 9 patients had no residual stones. Conclusion RVS applied in complicated hepatolithiasis is helpful for the precise intraoperative diagnosis, and the surgical treatment can be safe and effective.