Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:To investigate the effects of transepithelial photorefractive keratectomy (TransPRK) and femtosecond small incision lenticule extraction (SMILE) on corneal biomechanics measured by the Ocular Response Analyzer in the early postoperative period.Methods:A cohort study was conducted.The right eyes of 56 patients who underwent TransPRK and 52 patients who underwent SMILE in Dalian Medical University Affiliated Dalian Third People's Hospital from November 2020 to June 2021 were continuously included.The postoperative follow-up was 3 months.The central corneal thickness (CCT) and keratometry (Km) were measured 1 month and 3 months after surgery.The corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF), corneal hysteresis (CH), and 19 repeatable mechanical infrared signal waveform parameters measured by the Ocular Response Analyzer were recorded before the surgery, 1 month and 3 months after the surgery, respectively.The measurement indexs at different time points between two groups were compared.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Dalian Medical University Affiliated Dalian Third People's Hospital (No.2019-KT-010). Written informed consent was obtained from each patient before surgery.Results:There was no significant difference in CCT, Km, and IOPcc between the two groups at 1 month and 3 months after the surgery (all at P>0.05). In both groups, CRF, CH, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h1, h2, h11, h21, dive1, dive2 and mslew1 were decreased, while path1, path2, path11, and aplhf were increased at 1 month after the surgery compared with before surgery, showing statistically significant differences (all at P<0.05). In both groups, CRF, CH, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h1, h2, h11, h21, dive1 decreased, while path1, path2, path11, and aplhf were increased at 3 months after the surgery in comparison with before surgery, showing statistically significant differences (all at P<0.05). In SMILE group, the dive2 were decreased at 3 months after the surgery compared with before surgery, and the difference was statistically significant ( P<0.01). At 1 month after the surgery, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, dive1 and dive2 were higher, while CH, path1, path2, and path11 were smaller in TransPRK group than in SMILE group, showing statistically significant differences between them (all at P<0.05). At 3 months after the surgery, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h2, h21, dive1 and dive2 were higher, while path1, path2, and path11 were smaller in TransPRK group than in SMILE group, showing statistically significant differences between them (all at P<0.05). Conclusions:Corneal biomechanics are weakened after both TransPRK and SMILE.In the early postoperative period, the mechanical infrared waveform parameters measured by the Ocular Response Analyzer are better after TransPRK than after SMILE.

Objective:To investigate the differences and changes in early postoperative visual quality after small incision lenticule extraction (SMILE) and smart pulse technology-assisted transepithelial photorefractive keratectomy (SPT-TransPRK).Methods:A cohort study was performed.A total of 92 patients (92 eyes) who underwent corneal laser refractive surgery were enrolled in Dalian Third People's Hospital Affiliated to Dalian Medical University from February 2021 to May 2021.The data from the right eye were collected for analysis.The patients were divided into SMILE group (40 patients, 40 eyes) and SPT-TransPRK group (52 patients, 52 eyes). Preoperative, 1- and 3-month postoperative visual acuity were measured to calculate the effectiveness, which was defined as the ratio of postoperative uncorrected visual acuity (UCVA) to preoperative best corrected visual acuity.Refraction was measured by an AR-1 autorefractor.Corneal higher-order aberration (HOA) including total HOA, spherical aberration and coma was measured by Sirius corneal topographer.Objective scatter index (OSI), modulation transfer function cut-off frequency (MTF cut-off), Strehl ratio (SR), simulated contrast visual acuity VA100 (day), VA20 (dusk) and VA9 (night) were measured via OQAS II visual quality analysis system.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Dalian Third People's Hospital Affiliated to Dalian Medical University (No.2019-KT-010). Written informed consent was obtained from each subject.Results:There was no significant difference in 3-month postoperative UCVA and effectiveness between the two groups ( Z=0.880, P=0.380; t=0.920, P=0.058). Patients in SPT-TransPRK group showed mild hyperopia 3 months after surgery.Preoperative, 1- and 3-month postoperative total corneal HOA was (0.47±0.18), (0.70±0.22) and (0.74±0.19)μm in SMILE group, and (0.40±0.14), (0.98±0.35) and (0.94±0.22)μm in SPT-TransPRK group respectively, showing statistically significant differences ( Fgroup=13.851, P=0.001; Ftime=29.960, P<0.001). Preoperative, 1- and 3-month postoperative spherical aberration was (-0.20±0.09), (-0.44±0.14) and (-0.44±0.15)μm in SMILE group, and (-0.20±0.10), (-0.71±0.23) and (-0.75±0.20)μm in SPT-TransPRK group respectively, showing statistically significant differences ( Fgroup=31.037, P<0.001; Ftime=48.005, P<0.001). The postoperative total corneal HOA and spherical aberration were increased in both groups compared with before surgery, with statistically significant differences (all at P<0.05). The 1- and 3-month postoperative total corneal HOA and spherical aberrations were smaller in SMILE group than in SPT-TransPRK group, and the differences were statistically significant (all at P<0.05). The 1- and 3-month postoperative coma were increased in both groups compared with before surgery, showing statistically significant differences (all at P<0.05). In SMILE group, 1-month postoperative OSI was higher and 1-month postoperative MTF cut-off, SR, and VA9 were lower than those before surgery, and 3-month postoperative OSI was higher and 3-month postoperative SR and VA9 were lower than those before surgery, showing statistically significant differences (all at P<0.05). In SPT-TransPRK group, 1-month postoperative OSI was higher and 1-month postoperative MTF cut-off, SR, VA100, VA20, and VA9 were lower than those before surgery, showing statistically significant differences (all at P<0.05). There was no significant difference in OSI, MTF cut-off, SR, VA100, VA20, and VA9 between 3 months postoperatively and before surgery in the SPT-TransPRK group (all at P>0.05). There was no significant difference in coma, OSI, MTF cut-off, SR, VA100, VA20, and VA9 between two groups (all at P>0.05). Conclusions:Both SMILE and SPT-TransPRK are effective methods for correcting myopia and they have comparable visual quality.Compared with SPT-TransPRK, corneal total HOA and spherical aberration are smaller after SMILE.

OBJECTIVE To investigate the effects of individualized dosing regimen on blood trough concentration of vancomycin and renal function in critically ill patients. METHODS According to relevant guidelines and the results of Vancomycin Calculator， clinical pharmacists formulated an individualized dosing regimen of vancomycin including loading dose and maintenance dose for critically ill patients based on the two independent variables of body weight and creatinine clearance rate. Using the method of retrospective study， patients who were admitted to the department of intensive care unit （ICU） of the Second Affiliated Hospital of Guangzhou Medical University and used the regimen from July 2018 to December 2021 were selected as the trial group， and patients who were treated with vancomycin and received blood drug concentration monitoring in ICU from January 2015 to June 2018 were recruited in the control group. The difference in trough concentration distribution and the incidence of acute kidney injury （AKI） after medication were compared between the two groups， the change of serum creatinine before and after medication in the trial group was analyzed. RESULTS Totally 197 patients were included in the trial group and 144 patients were in the control group. There was no significant difference between the two groups in the clinical information （gender， age， body weight， acute physiology and chronic health evaluation Ⅱ score， the proportion of patients with renal insufficiency， etc.） （P＞0.05）. The proportions of major infection sites （including lung， urinary， abdominal， blood and central nervous system） and treatment type （target or empirical treatment） also had no significant difference between the two groups （P＞0.05）. There was no significant difference in the attainment rate of ideal trough concentration （15-20 μg/mL） and the proportion of patients with trough concentration　＞20 μg/mL between the two groups （P＞0.05）， while the attainment rate of target trough concentration （10-20 μg/mL） and the proportion of patients with trough concentration ＜10 μg/mL were significantly different between the two groups （P＜0.05）. The attainment rate of target trough concentration in patients with chronic renal insufficiency in trial group was significantly higher than that in control group （P＜0.05）. There was no significant difference in the incidence of AKI and vancomycin-associated AKI between the two groups （P＞0.05）. In the trial group with medication duration ≥7 days ， the level of serum creatinine on the 7th day of treatment was increased significantly， compared with that on the 3rd day of treatment （P＜0.05）. CONCLUSIONS This individualized dosing regimen can improve the attainment rate of target trough concentration of vancomycin in critically ill patients， especially those with chronic renal insufficiency， during the first standardized monitoring， and not increase the risk of renal injury compared with previous empirical medication.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective:To explore the mechanism of pioglitazone in reducing lung injury induced by acute pancreatitis.Methods:Thirty healthy male SD rats were randomly(random number) divided into the sham operation group, model group and pioglitazone group, with 10 rats in each group. After anesthesia, the rats in the sham operation group were injected with normal saline retrogradely through the pancreaticobiliary duct. In the model group, after anesthesia, the rats were retrogradely injected with sodium taurocholate into the pancreaticobiliary duct to construct the lung injury model of severe acute pancreatitis. In the pioglitazone group, the model was established after intraperitoneal injection of pioglitazone. Six rats in each group were randomly selected and killed 12 h after operation, and then lung tissue and venous blood were collected. The levels of serum amylase and TNF-α and NO in lung tissue homogenate were detected and compared among the three groups; the expression of TLR2 mRNA and TLR4 mRNA in lung tissue was detected by RT-PCR and compared among the three groups; the lung tissue pathological injury score and lung leakage index were calculated and compared among the three groups. The correlation of TLR2 and TLR4’s mRNA expression with lung tissue pathological injury score and lung leakage index was analyzed.Results:The levels of serum amylase and the levels of TNF-α and NO in lung tissue homogenate in the model group were significantly higher than those in the sham operation group, and the above indexes in the pioglitazone group were significantly lower than those in the model group ( P<0.05). The expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue, the lung tissue pathological injury score and lung leakage index in the model group were significantly higher than those in the sham operation group, and the above indexes in the pioglitazone group were significantly lower than those in the model group ( P<0.05). Spearman correlation analysis showed that the expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue were significantly positively correlated with the lung tissue pathological injury score ( rs=0.959, P<0.001; rs=0.924, P<0.001). Pearson correlation analysis showed that the expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue were significantly positively correlated with the lung leakage index ( r=0.957, P<0.001; r=0.958, P<0.001). Conclusions:Pioglitazone may reduce the severity of severe acute pancreatitis induced lung injury by inhibiting the expression of TLR2 mRNA and TLR4 mRNA in lung tissue.

Objective:To explore the mechanism of miR-494 negatively regulating ROCK1 and PTEN in inhibiting apoptosis of pancreatic cells and participating in the occurrence and development of acute pancreatitis.Methods:Pancreatic acinar cells AR42J from rats were treated by caerulein, and then the levels of amylase, tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1) and IL-6 in the supernatant of cell culture were detected by ELISA to verify the cell model of acute pancreatitis. RT-PCR was used to detect the expression of miR-494 in normal AR42J cells (control group) and acute pancreatitis cell model (model group). Flow cytometry was used to detect the apoptosis of the control group, negative control miRNA transfected acute pancreatitis cell model (negative control group) and miR-494 transfected acute pancreatitis cell model (miR-494 transfection group). Western blot was used to detect the expression of ROCK1 and PTEN in the control group, negative control group and miR-494 transfection group.Results:The levels of amylase, TNF-α, IL-1 and IL-6 in the supernatant of AR42J cells treated with caerulein for 8 h and 12 h were significantly higher than those at 0 h and the control group ( P<0.05), indicating that the model was successfully constructed. The expression levels of miR-494 at 8 h, 12 h and 24 h after the establishment of acute pancreatitis cell model were significantly higher than those at 4 h and the control group ( P < 0.05). The apoptosis rate of the model group was significantly higher than that of the control group ( P<0.05), and the apoptosis rate of the miR-494 transfection group was significantly lower than that of the model group ( P<0.05). The expression levels of ROCK1 and PTEN in the miR-494 transfection group were significantly lower than those in the model group and negative control group ( P<0.05). Conclusions:When acute pancreatitis occurs, overexpression of miR-494 can inhibit the expression of pro-apoptotic protein, thus inhibiting the apoptosis of pancreatic acinar cells and promoting the development of acute pancreatitis.

OBJECTIVE: To analyze the clinical manifestations of heart, liver and kidney damages in the early stage of COVID-19 to identify the indicators for these damages. METHODS: We analyzed the clinical features, underlying diseases, and indicators of infection in 12 patients with COVID-19 on the second day after their admission to our hospital between January 20 and February 20, 2020.The data including CK-MB, aTnI, BNP, heart rate, changes in ECG, LVEF (%), left ventricular general longitudinal strain (GLS, measured by color Doppler ultrasound) were collected.The changes of liver function biochemical indicators were dynamically reviewed.BUN, UCR, eGFR, Ccr, and UACR and the levels of MA, A1M, IGU, and TRU were recorded. RESULTS: The 12 patients included 2 severe cases, 8 common type cases, and 2 mild cases.Four of the patients presented with sinus tachycardia, ECG changes and abnormal GLS in spite of normal aTNI and LVEF; 1 patient had abnormal CKMB and BNP.On the first and third days following admission, the patients had normal ALT, AST and GGT levels.On day 7, hepatic function damage occurred in the severe cases, manifested by elevated ALT and AST levels.Abnormalities of eGFR, Ccr and UACR occurred in 8, 5 and 5 of the patients, respectively.Abnormal elevations of MA, A1M, IGU and TRU in urine protein were observed in 4, 4, 5, and 2 of the patients, respectively. CONCLUSIONS In patients with COVID-19, heart damage can be identified early by observing the GLS and new abnormalities on ECG in spite of normal aTNI and LVEF.Early liver injury is not obvious in these patients, but dynamic monitoring of the indicators of should be emplemented, especially in severe cases. In cases with normal CR and BUN, kidney damage can be detected early by calculating eGFR, Ccr and UACR and urine protein tests.
Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2