OBJECTIVE: To evaluate the prognosis of septic right ventricular dysfunction (SRVD) based on bedside ultrasound and explore its risk factors. METHODS: A prospective observational study was conducted involving septic and septic shock patients admitted to the intensive care unit (ICU) of the General Hospital of Ningxia Medical University from February 2021 to January 2022. Tricuspid annular plane systolic excursion (TAPSE) was measured by M-mode ultrasound within 24 hours after ICU admission. According to the results of TAPSE, the subjects were divided into SRVD group (TAPSE < 16 mm) and non-SRVD group (TAPSE ≥ 16 mm). The gender, age, occurrence of septic shock, underlying diseases, source of patients, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, maximal body temperature within 24 hours after ICU admission, location and number of infections, duration of mechanical ventilation, and 28-day mortality were collected. Hemodynamic parameters, organ function indexes, oxygen therapy parameters and arterial blood gas analysis indexes were recorded within 24 hours after ICU admission. The differences of the above indexes between the two groups were compared. Binary multivariate Logistic regression analysis was used to screen out the independent risk factors for SRVD, and a nomogram of SRVD risk factors was drawn. RESULTS: 116 patients with sepsis and septic shock were enrolled, of which 24 (20.7%) had SRVD and 92 (79.3%) had no SRVD. Compared with the non-SRVD group, the patients in the SRVD group had higher emergency transfer and infection site ≥ 2 ratio, APACHE II score, SOFA score, higher cardiac troponin I (cTnI), myoglobin (Mb), MB isoenzyme of creatine kinase (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), serum creatinine (SCr), arterial blood lactic acid (Lac) and lower left ventricular ejection fraction (LVEF), platelet count (PLT) within 24 hours after ICU admission, and higher proportion of norepinephrine application and continuous renal replacement therapy (CRRT). Binary multivariate Logistic regression analysis showed that LVEF [odds ratio (OR) = 0.918, 95% confidence interval (95%CI) was 0.851-0.991, P = 0.028], PLT (OR = 0.990, 95%CI was 0.981-0.999, P = 0.035), SCr (OR = 1.008, 95%CI was 1.001-1.016, P = 0.025), and the usage of norepinephrine (OR = 15.198, 95%CI was 1.541-149.907, P = 0.020) were independent risk factors for SRVD in patients with sepsis and septic shock. Based on the above four independent risk factors, a nomogram of SRVD risk factors was drawn. The results showed that the score was 64 when LVEF was 0.50, 18 when SCr was 100 μmol/L, 85 when PLT was 100×10⁹/L, and 39 when norepinephrine was used. When the total score reached 253, the risk of SRVD was 88%. Compared with non-SRVD group, the duration of mechanical ventilation in SRVD group was slightly longer [hours: 80.0 (28.5, 170.0) vs. 47.0 (10.0, 135.0), P > 0.05], and the 28-day mortality was significantly higher [41.7% (10/24) vs. 21.7% (20/92), P < 0.05]. CONCLUSIONS Patients with sepsis may have right ventricular dysfunction, impaired renal function and increased mortality in the early stage. The decrease in LVEF and PLT, the increase in SCr and the application of norepinephrine are independent risk factors for SRVD in patients with sepsis.
Humans ; Prognosis ; Ventricular Dysfunction, Right/diagnostic imaging* ; Risk Factors ; Prospective Studies ; Intensive Care Units ; Shock, Septic ; Male ; Ultrasonography ; Female ; Sepsis/complications* ; Middle Aged ; Point-of-Care Systems ; Aged ; Logistic Models ; APACHE

OBJECTIVE To analyze the clinical characteristics of liraglutide-induced pancreatitis， and to provide reference for clinical rational drug use. METHODS Retrieved from CNKI， VIP， Wanfang database， PubMed， Web of Science and Medline， case reports about liraglutide-induced pancreatitis were collected from the inception to December 31st， 2022. Demographic characteristics， drug use， clinical manifestations， intervention and outcome were analyzed using descriptive statistical method. RESULTS A total of 17 pieces of literature were collected and 17 patients were involved， including 7 males and 10 females. The patients aged from 25 to 75 years. All 17 patients had drug indications， including 14 cases of type 2 diabetes mellitus， 3 cases of obesity or overweight. Among 17 patients， liraglutide was used alone in 5 cases， and combined with other drugs in 12 cases. Time from liraglutide administration to pancreatitis occurrence ranged from 1 day to 11 months after medication in 17 patients， with 14 cases less than 6 months. The clinical manifestations mainly included abdominal pain， nausea and vomiting， etc. After the diagnosis of pancreatitis， liraglutide discontinuation occurred in 16 patients； 1 case did not receive any other interventions and the other 15 cases were managed with symptomatic supportive treatment； the symptoms of all 16 patients resolved； however， 2 patients suffered from second episode of severe pancreatitis several weeks after liraglutide discontinuation， pancreatitis recurred after liraglutide rechallenge in 1 case. The results of correlation evaluation showed that 1 case was “positive”， 4 cases were “possible”， and the remaining patients were “very likely”. CONCLUSIONS Liraglutide-induced pancreatitis mainly occurred within 6 months after drug administration. The majority of liraglutide-induced pancreatitis cases are mild to moderate， but there are also severe and even fatal cases. It is advisable to periodically monitor the level of pancreatic enzymes and closely observe patients’ clinical mani-festations. In case of suspected liraglutide-induced pancreatitis，drug withdrawal and symptomatic treatment should be taken immediately.

Objective To investigate the effect of aspirin-induced Gasdermin E(GSDME)dependent pyroptosis and the related mechanism of colorectal cancer cell proliferation.Methods The colorectal cancer cells Caco2 were cultured in vitro.MTT assay was used to detect the effects of aspirin intervention with different concentrations(1.0,2.5,5.0,10.0,15.0,20.0 mmol/L)on the proliferation activity of colorectal cancer cells.The effect of aspirin intervention on the morphology of colorectal cancer cells was observed under the microscope.Lactate dehy-drogenase(LDH)release assay was used to investigate the effect of aspirin intervention on cell membrane integrity.The protein expression levels of NOD-like receptor protein(NLRP3),cysteinyl aspartate and specific proteinase 1(Caspase-1),Gasdermin E-N(GSDME-N)in colorectal cancer cells were detected by Western blot.The contents of interleukin-1 β(IL-1 β)and interleukin-18(IL-18)in cell supernatant after GSDME silencing were detected by ELISA.After silencing GSDME,cell morphological changes were observed under a microscope,and cell membrane integrity was observed by LDH release assay;The contents of IL-1 β and IL-18 in cell supernatant were determined by ELISA after GSDME silencing.Results MTT results showed that aspirin could decrease the proliferation activi-ty of Caco-2 in a concentration-dependent manner(P＜0.01).Morphological observation and LDH experiment showed that aspirin could promote the occurrence of pyroptosis(P＜0.05).Western blot showed that aspirin could increase the expression levels of NLRP3,Caspase-1,GSDME-N of pyroptosis-related pathway genes(P＜0.05).ELISA showed that aspirin could significantly increase the concentration of IL-1 β and IL-18 in Caco-2 cells(P＜0.01).After GSDME silencing,the pyroptosis was significantly inhibited(P＜0.05)and the expression of IL-1 βand IL-18 decreased significantly(P＜0.01).Conclusion Aspirin can inhibit the proliferation of Caco-2 by indu-cing the pyroptosis of GSDME-dependent cells,thus inhibiting colon cancer.

Platelets are important components of the blood system. There are many kinds of concentrated platelets and their derivatives, among which platelet-rich plasma (PRP ), growth factors (GFs) and platelet-rich fibrin (PRF) have been widely used in clinical practice. Lyophilized platelets (Lyo-P) or freeze-dried platelets (FDP) are prepared from concentrated platelets by freeze-drying and have the advantages of long storage time at room temperature, light weight, convenient transportation, inactivation of pathogens, etc. Lyo-P contain high concentration of GFs, fibrin, white blood cells and various cytokines. In addition to their hemostatic and coagulative functions, Lyo-P and their products are increasingly used in wound healing, tissue repair, cosmetology, reproductive medicine and other fields.

Neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) are a heterogeneous group of disorders characterized by progressive degeneration of neurons. NDDs threaten the lives of millions of people worldwide and regretfully remain incurable. It is well accepted that dysfunction of mitochondria underlies the pathogenesis of NDDs. Dysfunction of mitochondria results in energy depletion, oxidative stress, calcium overloading, caspases activation, which dominates the neuronal death of NDDs. Therefore, mitochondria are the preferred target for intervention of NDDs. So far various mitochondria-targeting drugs have been developed and delightfully some of them demonstrate promising outcome, though there are still some obstacles such as targeting specificity, delivery capacity hindering the drugs development. In present review, we will elaborately address 1) the strategy to design mitochondria targeting drugs, 2) the rescue mechanism of respective mitochondria targeting drugs, 3) how to evaluate the therapeutic effect. Hopefully this review will provide comprehensive knowledge for understanding how to develop more effective drugs for the treatment of NDDs.

Cutaneous chronic wounds are a major global health burden in continuous growth due to population aging and the higher incidence of chronic diseases, such as diabetes. In the process of spontaneous wound healing, growth factors play a vital role. Thanks to the high content of growth factors in platelet rich plasma(PRP), more and more PRP has been used to treat chronic refractory wounds, including diabetic ulcer, pressure ulcer, venous ulcer, and burns, etc., and has achieved significant results. Given the short duration of local growth factor release in the wound when PRP is applied alone, some studies have combined PRP with different tissue biology materials, such as hyaluronic acid, chitosan, and chitosan derivatives, to achieve better therapeutic results. In this paper, the preparation method of PRP, the mechanism of growth factors, the effect of PRP on wound repair, the combined application of PRP with repair materials and the advantages and disadvantages of PRP are reviewed.

Objective : To investigate the effect of chemotherapeutic drug resistance induced by CLDN18⁃ARH⁃GAP26 fusion mutation gene in gastric cancer cells , and to investigate the sensitization effect of ginsenoside in the treatment of chemotherapeutic drug resistance caused by the expression of CLDN18⁃ARHGAP26 fusion mutation gene. Methods : The side population (SP) cells and non⁃side population ( NSP) cells of gastric cancer cell line BGC⁃823 were labeled with immunomagnetic bead antibody , and the lentiviral vector with overexpression of CLDN18⁃ARHGAP26 fusion mutation gene was selected for transfection with NSP cells. qPCR was used to detect the mRNA levels of CLDN18⁃ARHGAP26 fusion mutation and ATP Binding Cassette Subfamily G Member 2 (ABCG2) . The expression of EMT⁃related proteins E ⁃Cadherin and Vimentin was detected by Western blot. The sensitivity of transfected cells to oxaliplatin was detected by CCK⁃8. The effect of ginsenoside on drug resistance of transfected cells was detected by CCK ⁃ 8 . The expression of E ⁃ Cadherin and Vimentin in transfected cells was detected by Western blot after ginsenoside treatment. Results : qPCR detection showed that the expression of CLDN18⁃ARH⁃GAP26 fusion mutant gene in NSP cells transfected with overexpressed CLDN18⁃ARHGAP26 fusion mutant gene was significantly higher than that of the non⁃transfected group , and the expression of ABCG2 mRNA was significantly cells with over⁃expressed CLDN18⁃ARHGAP26 fusion mutation gene was lower than that in the non⁃transfected transfected cells to oxaliplatin was lower than that in the non⁃transfected group. The survival rate of transfected cells sion of E ⁃Cadherin protein in the transfected cells treated with ginsenoside was higher than that in the untreated group , and the expression of Vimentin protein was lower than that in the untreated group. Conclusion Ginsenoside can reverse cell EMT transformation and oxaliplatin resistance induced by CLDN18⁃ARHGAP26 fusion mutated gene expression in gastric cancer tissues.

Objective     To analyze the perioperative outcomes of uniportal thoracoscopic lobectomy compared with three-port thoracoscopic lobectomy. Methods     Data were extracted from the Western China Lung Cancer Database, a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital, Sichuan University. Perioperative outcomes of the patients who underwent uniportal or three-port thoracoscopic lobectomy for lung cancer during January 2014 through April 2021 were analyzed by using propensity score matching. Altogether 5 817 lung cancer patients were enrolled who underwent thoracoscopic lobectomy (uniportal: 530 patients; three-port: 5 287 patients). After matching, 529 patients of uniportal and 1 583 patients of three-port were included. There were 529 patients with 320 males and 209 females at median age of 58 (51, 65) years in the uniportal group and 1 583 patients with 915 males and 668 females at median age of 58 (51, 65) years in the three-port group. Results     Uniportal thoracoscopic lobectomy was associated with less intraoperative blood loss (20 mL vs. 30 mL, P<0.001), longer operative time (115 min vs. 105 min, P<0.001) than three-port thoracoscopic lobectomy. No significant difference was found between the two groups regarding the number of lymph node dissected, rate of conversion to thoracotomy, incidence of postoperative complication, postoperative pain score within 3 postoperative days, length of hospital stay, or hospitalization expenses. Conclusion     Uniportal video-assisted thoracoscopic lobectomy is safe and effective, and the overall perioperative outcomes are comparable between uniportal and three-port strategies, although the two groups show differences in intraoperative blood loss.

Objectives: To compare the impact of ticagrelor or clopidogrel on serum uric acid levels among patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) and further evaluate the effects of variation of serum uric acid levels on platelet reactivity. Methods: STEMI patients who admitted to Fuwai Hospital from April 2017 to January 2020, and underwent primary PCI and discharged alive with aspirin and ticagrelor or clopidogrel were included in this study. Patients were divided into ticagrelor group and clopidogrel group. The baseline clinical data were collected. Serum uric acid and creatinine levels at baseline and 30 days post-PCI were measured. Light transmittance aggregometry was used to assess maximum aggregation rate induced by adenosine diphosphate and arachidonic acid. The changes of serum uric acid and creatinine were compared between the two groups. Multivariate logistic regression was performed to evaluate independent related factors for rise in the uric acid levels, and the effect of variation of serum uric acid level on platelet reactivity was analyzed. Results: A total of 967 patients were included, the age was (59.4±12.1) years, and 163 case were female. There were 550 cases in ticagrelor group (56.9%) and 417 cases in clopidogrel group (43.1%). Baseline serum uric acid and creatinine levels were similar between the 2 groups. At 30 days, the serum uric acid level [(347.2±96.5) mmol/L vs. (341.2±105.3) mmol/L, P=0.009] and absolute [46.4 (-2.4, 88.1) mmol/L vs. 25.0 (-21.9, 73.0) mmol/L, P=0.001] and percentage [13.2 (-0.01, 29.0) % vs. 7.9 (-5.7, 25.0) %, P=0.007] increase in the serum uric acid levels were significantly higher in ticagrelor group than in clopidogrel group. The level of serum creatinine at 30 days was significantly lower in ticagrelor group than in clopidogrel group [(89.7±21.3) μmol/L vs. (94.4±43.9) μmol/L, P<0.05], whereas there were no differences in absolute [8.0 (-1.4, 16.6) μmol/L vs. 7.8 (-2.0, 16.6) μmol/L] and percentage [10.5 (-1.7%, 22.6%) vs. 9.8 (-2.4%, 22.1%)] change in the serum creatinine between the 2 groups (all P>0.05). Logistic regression analysis showed that, after adjusting for confounding factors, ticagrelor therapy was an independent related factor of serum uric acid elevation (OR=1.582, 95% CI:1.023-2.447, P=0.039). The variation of the serum uric acid levels did not affect platelet aggregation and the percentage of high platelet reactivity in both groups. Conclusions: Ticagrelor use is related to a significant increase in the serum uric acid levels at 30 days post-PCI in this patient cohort. The variations in the uric acid levels do not increase the percentage of high platelet reactivity in STEMI patients treated with ticagrelor or clopidogrel.
Adenosine/therapeutic use* ; Aged ; Female ; Humans ; Middle Aged ; Myocardial Infarction/drug therapy* ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; ST Elevation Myocardial Infarction ; Ticagrelor/therapeutic use* ; Ticlopidine ; Time Factors ; Treatment Outcome ; Uric Acid

Objective:To investigate the clinical characteristics and risk factors of lymph node metastasis of early gastric cance.Methods:The data of 176 early gastric cancer patients (EGC) undergoing radical gastrectomy were analyzed retrospectively.Results:Lymph node (LN) metastasis occurred in 24 patients. The average harvested LN in the negative group was 23±13, and that in the positive group was 30±16, ( t=0.327, P=0.015). Univariate analysis showed that there were significant differences in the depth of tumor invasion ( χ2=3.997, P=0.046), degree of pathological differentiation ( χ2=9.919, P=0.007), vascular invasion ( χ2=35.145, P=0.000) and nerve invasion ( χ2=13.343, P=0.000). Multivariate analysis showed that vascular infiltration ( OR=16.172, 95% CI: 4.781-55.875), nerve infiltration ( OR=1.365, 95% CI: 1.029-14.897), infiltration depth ( OR=1.859, 95% CI: 1.844-22.711) were independent risk factors for LN metastasis in early gastric cancer ( P<0.05). The overall 3-year survival rate was 96.6%, and the 5-year survival rate was 91.6%. Conclusion:The lymph node metastasis of early gastric cancer is related to the degree of differentiation, the depth of invasion, vascular invasion, nerve invasion and the number of lymph node dissected.