[Comparative study of ultrasound and magnetic resonance imaging in the diagnosis of asymptomatic anterosuperior acetabular labrum tears].

OBJECTIVE: To explore the diagnostic value of ultrasound for asymptomatic anterosuperior acetabular labral tears (ALT). METHODS: From August 2018 to February 2020, a total of 64 asymptomatic volunteers (101 hips) were recruited to complete 3.0T magnetic resonance imaging (MRI) and ultrasound examination. Among these asymptomatic volunteers, 31 were male and 33 were female, with the median age 35 (32, 39) years. Using 3.0T MRI findings as golden standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound were calculated. RESULTS: The results showed the presence of unilateral or bilateral ALT in 33 (51.56%) asymptomatic vo-lunteers with a total of 47 hips (46.53%). Of the 37 asymptomatic volunteers with bilateral hip MRI examination, 14 had bilateral ALT and 8 had unilateral ALT. Of the 27 asymptomatic volunteers who underwent unilateral hip MRI, 11 had ALT. Of the 33 asymptomatic volunteers with labral tears, 11 were male and 22 were female, with 30 right hips and 17 left hips. The median age was 36 (33, 40) years in the ALT group and 34 (32, 38) years in the non-ALT group. There was no significant difference in age between the two groups (P > 0.05). In the asymptomatic population, the abnormal anterosuperior acetabular labrum manifestations on ultrasound were intra-labrum cleft in 26 cases, labral heterogeneous echogenicity in 25 cases, paralabral cysts in 2 cases, and labral focal hyperechoic area in 12 cases. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for ALT diagnosed by ultrasound were 73.53%, 67.16%, 53.19%, 83.33% and 69.31%, respectively. The cross- sectional area (CSA) of the anterosuperior acetabular labrum was 0.20 (0.15, 0.24) cm2 in this study. The labral median CSA of the ALT group and non-ALT group were 0.22 (0.17, 0.28) cm2 and 0.17 (0.14, 0.21) cm2, respectively, with a statistically significant difference (P < 0.001). CONCLUSION: The ALT are common findings in asymptomatic volunteers on MRI. Intra-labrum cleft and labral heterogeneous echogenicity are common ultrasonographic signs in asymptomatic volunteers with ALT. The labra were more swollen in the asymptomatic volunteers with ALT compared to those without ALT.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Clinical analysis of penetrating keratoplasty for infants with congenital corneal opacity].

Objective: To investigate the corneal graft survival and related risk factors of primary penetrating keratoplasty in congenital corneal opacity infants. Methods: It was a retrospective cohort study. Data were collected from forty-two infants (51 eyes) who were aged ≤12 months and diagnosed with congenital corneal opacity in Beijing Tongren Hospital and Beijing Anzhen Hospital from January 1, 2017 to January 31, 2018. The mean age at surgery was (5.7±2.2) months (3-12 months). The mean follow-up duration was (28.6±2.6) months (24-33 months). All the patients underwent penetrating keratoplasty. The status of the corneal grafts and complications were observed and recorded during the regular follow-up. The survival probabilities were estimated by using the Kaplan-Meier and Log-rank test. The graft survival between different influence factors was analyzed by using the χ2 test. Results: The Kaplan-Meier survival rates for penetrating keratoplasty were 84.3% (43/51) at 6 months, 78.4% (40/51) at 12 months and 60.8% (31/51) at the last follow-up. The presence of corneal neovascularization was significantly correlated with graft failure (χ²=5.264, P=0.022). The graft survival differed between eyes receiving combined surgery and mere penetrating keratoplasty and in eyes with varied surgical indications (P=0.039, <0.01). Increased intraocular pressure (7 eyes, 13.7%) and persistent epithelial defects (7 eyes, 13.7%) were the most common postoperative complications, followed by complicated cataract (4 eyes, 7.8%) and posterior capsule opacification (2 eyes, 3.9%). Conclusions: The graft survival rate was satisfactory following pediatric keratoplasty although it had a tendency to decrease with the follow-up time. Corneal neovascularization was a major risk factor of graft failure. Surgical indications and procedures also had a certain effect on the graft survival.

Comparison of clinical diagnostic value of spiral CT with different dose in patients with early-stage peripheral lung cancer.

PURPOSE: To compare the clinical diagnostic value of spiral CT scan with different dose in patients with early-stage peripheral lung cancer. METHODS: A total of 163 cases of patients with early-stage peripheral lung cancer who came to People's Hospital of Rizhao for treatment from June 2014 to January 2017 were retrospectively analyzed. A total of 78 cases of patients who received low-dose CT scanning were the low-dose group, another 84 cases of patients who received routine dose CT scanning were the routine dose group. Multislice helical CT (MSCT) scanning was performed in both groups, with tube voltage of 120 kV. Tube current was 25 m A in the low-dose group and 250 m A in the routine dose group. In addition, a total of 80 patients with lobar pneumonia were added as the control group of diagnostic sensitivity, specificity and accuracy. Pathological diagnosis was taken as the gold standard to compare the diagnostic sensitivity, specificity and accuracy of the two groups. RESULTS: The image quality, nodules and signs of the two groups were compared, and the results of radiation dose of the two groups were compared. The diagnostic sensitivity, specificity and accuracy of the low-dose group were 82.05%, 87.50% and 84.81%, respectively. The diagnostic sensitivity, specificity and accuracy of the routine dose group were 85.71%, 86.25% and 85.97%, respectively. The diagnostic value of the two groups was not statistically significant (p > 0.05). However, the radiation dose in the low-dose group was significantly lower than that in the routine group. CONCLUSION: Low-dose MSCT scanning can meet the clinical requirements for imaging diagnosis of peripheral lung cancer, and can reduce the radiation dose of patients.

[Analysis of BK virus infection in kidney transplant recipients].

Objective: To compare the infection of BK virus in the recipients of living donor(LD) kidney transplant and deceased donor(DD) kidney transplant. Methods: A total of 911 recipients who underwent kidney transplantation in the Organ Transplantation Research Institute of the 8th Medical Center of the People's Liberation Army General Hospital from January 2015 to August 2019 were enrolled in this study. The DNA copies of BK virus in urine and peripheral blood of kidney transplant recipients were detected by real-time quantitative PCR. The patients were divided into LD group (n=255) and DD group (n=656). BK virus infection in recipients with DD kidney transplant were compared with that in recipients of LD kidney transplant. Results: The BK virus positive rate in the urine of all subjects was 13.06%(119/911), and that in blood was 2.96% (27/911). The positive rate of BK virus in urine after kidney transplantation was significantly higher than that in blood(P<0.000 1). The positive rate in urine was 9.02% (23/255) in LD group, which was significantly lower than that of 14.63% (96/656) in DD group in the same period (χ(2)=5.097, P=0.012); The positive rate of BK virus infection in relatives group was 0.78% (2/255), which was significantly lower than that of 3.81% (25/656) in DD group (χ(2)=5.849, P=0.007). Conclusions: There was a significant difference in the infection rate of BK virus between the LD and DD group. The incidence of BK virus infection in kidney transplant recipients from DD was higher than that of from LD kidney transplant recipients.

[Study on the matching feature of current parameters for inducing contraction of orbicularis oris muscle by artificial facial nerve in rabbit with peripheral facial paralysis].

Objective: To explore the optimal matching of the current parameters about artificial facial nerve (AFN) for inducing contraction of the orbicularis oris muscle (OOM) in rabbit with peripheral facial paralysis. Methods: According to the combinations of different stimulus parameters, at different time points, we used AFN to induce contraction of the affected side OOM of the paralyzed rabbit in waking state. We recorded the current amplitudes of the threshold stimulation and peak stimulation under each combination, then compared the total charge of the stimulus consumption under different combinations. Results: Compared the total stimulus charge consumption of the AFN threshold stimulation and that in the peak stimulation respectively under different stimulus frequency and pulse width matching combinations, we found that the frequency, the pulse width and the interaction of the frequency and pulse width among different groups could affect the total charge, the differences were statistically significant (P<0.05). Conclusions: When AFN stimulus frequency is 60 Hz and the stimulus pulse width is 100 µs, the output current intensity is relatively lowest and the total consumed charge is the lowest under the premise of effectively inducing the paralytic side OOM contraction. Thus we recommend this stimulus parametric combination as the optimal combination for meeting the low power consumption of AFN.

[Surgical strategies and long-term outcomes of total arterial coronary artery bypass grafting: a series of 208 patients].

Objective: To examine the short and long-term clinical outcomes of total arterial coronary artery bypass grafting. Methods: Clinic data of 208 patients with left main and multiple vessel coronary artery disease and undertaken total arterial coronary artery bypass grafting from February 2009 to December 2019 in Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine were analyzed retrospectively. There were 188 males and 20 females with an age of (54.7±10.7) years (range: 32 to 79 years). The harvest of arterial conduits and grafting strategies were depended upon the individual patient characteristics and surgeon's experience. Left internal thoracic artery (LITA) was applied in 207 cases, right internal thoracic artery (RITA) in 38 cases (bilateral internal thoracic artery (BITA) in 37 cases), and radial artery (RA) in 187 cases (188 grafts). The graft number per case was 2.6±0.7 (range: 2 to 4). Surgical procedures was completed with off-pump technique in 98.1% patients (204/208). Subgroup analysis was carried out between subgroup BITA (n=37) and subgroup SITA (single ITA+RA) (n=171). The t test, χ(2) test or Fisher exact test were used to compare the clinic characteristics between the two subgroups. The Kaplan-Meier curve was used to estimate the rate of late mortality, major adverse cardiac cerebrovascular event (MACCE), and target vessel revascularization (TVR). A Cox proportional hazards model was used to identify the independent prognosis factors of late mortality. Results: The overall mortality within 30 days postoperatively was 1.4%(3/208). The incidences of perioperative MACCE, re-operation for bleeding and deep sternal wound infection (DSWI) were 1.9%(4/208), 0.5%(1/208) and 1.4%(3/208), respectively. Perioperative myocardial infarction and TVR were not observed. There was no significant difference of 30-day mortality, MACCE, bleeding and DSWI between subgroup BITA and SITA+RA (all P>0.05). In a follow-up period of (5.4±2.8)years (range: 0.2 to 10.9 years), the incidence of all-cause mortality at 1-, 5- and 10-year was 2.3%, 3.4% and 6.9%, respectively. The incidence of MACCE was 3.9%,11.2% and 28.5%, respectively. The rate of TVR was 0.4%, 3.7% and 11.9%, respectively. Age>65 was an independent prognosis factor of late mortality (HR=1.125, 95% CI:1.050 to 1.205, P<0.01). Conclusions: Total arterial coronary bypass grafting is safe and achievable with proper patient selection and surgical strategies. It significantly decreases the risks of late mortality and repeated revascularization.

[Restoration of orbicularis oculi muscle function with totally implanted artificial facial nerve].

Objective: To investigate the effect of the artificial facial nerve on the restoration of orbicularis oculi muscle function for unilateral peripheral facial paralysis in rabbit. Methods: Artificial facial nerve was implanted into the rabbit with unilateral peripheral facial paralysis between January 2018 and May 2019. At different time points after operation, the affected orbicularis oculi muscles' stimulation closure threshold and the synchronism about the motion of the two sides of orbicularis oculi muscles were monitored. T test was used with SPSS 13.0 software. Results: There was no significant difference in the closure threshold of the orbicularis oculi muscle on the 7th and 28th days after artificial facial nerve implantation (P>0.05). The synchronism of the normal side eye closing movement triggered the affected orbicular oculi muscle movement with the artificial facial nerve was up 19/20 to 20/20 at different times. Conclusions: The artificial facial nerve system had the features of stable working condition and high synchronizing effect for stimulating movement. It could restore the closed eye function in animals with peripheral facial paralysis animals and had great clinical application prospects.

Multiple antibodies targeting tumor-specific mutations redirect immune cells to inhibit tumor growth and increase survival in experimental animal models.

BACKGROUND: T cell therapy for cancer involves genetic introduction of a target-binding feature into autologous T cells, ex vivo expansion and single large bolus administration back to the patient. These reprogrammed T cells can be highly effective in killing cells, but tumor heterogeneity results in regrowth of cells that do not sufficiently express the single antigen being targeted. We describe a cell-based therapy that simultaneously targets multiple tumor-specific antigens. METHODS: High-affinity polyclonal rabbit antibodies were generated against nine different surface-related tumor-specific mutations on B16F10 cells. Unsorted splenic effector cells from syngeneic mice were incubated with a cocktail of the nine anti-B16F10 antibodies. These 'armed' effector cells were used to treat mice previously inoculated with B16F10 melanoma cells. RESULTS: The cocktail of nine antibodies resulted in dense homogeneous binding to histological sections of B16F10 cells. Five treatments with the armed effector cells and PD1 inhibition inhibited tumor growth and improved survival. Shortening the interval of the five treatments from every three days to every day increased survival. Arming effector cells with the four antibodies showing best binding to B16F10 cells even further increased survival. CONCLUSIONS: This study demonstrates that ex vivo arming a mixed population of immune effector cells with antibodies targeting multiple tumor-specific mutated proteins in conjunction with PD1 inhibition delayed tumor growth and prolonged survival in mice inoculated with an aggressive melanoma. A remarkably low total antibody dose of less than 5 µg was sufficient to accomplish tumor inhibition. Scaling up to clinical level may be feasible.

[Clinical effects and mechanism of treating extensive deep burns by stage-â ¡ Meek skin grafting on adipose tissue after tangential excision].

Objective: To observe the clinical effects of stage-Ⅱ Meek skin grafting on adipose tissue after tangential excision in patients with extensive deep burns, and to explore the functional mechanism. Methods: The medical records of 26 extensively burned patients who met the inclusion criteria and were admitted to the Department of Burns and Plastic Surgery of the Fourth Medical Center of PLA General Hospital from May 2015 to December 2017 were retrospectively analyzed. According to the treatment methods, 14 patients were enrolled in stage-Ⅰ skin grafting group (10 males and 4 females, aged 27 to 75 years), and 12 patients were enrolled in stage-Ⅱ skin grafting group (10 males and 2 females, aged 31 to 76 years). Patients in the 2 groups all underwent debridement of tangential excision, and their healthy adipose tissue was preserved. Meek skin grafting was performed just after tangential excision in patients in stage-Ⅰ skin grafting group. In patients in stage-Ⅱ skin grafting group, porcine acellular dermal matrix (ADM) was applied to cover the wound after tangential excision, and 3 days later, it was removed and Meek skin grafting was performed. The times of complement skin grafting and the wound basic healing time of patients in the 2 groups were observed and recorded. In the stage-Ⅱ skin grafting group, the adipose tissue of patients were taken from the wound center immediately after tangential excision and immediately after the removal of porcine ADM, for the observation of structure of the fault surface of adipose tissue through hematoxylin and eosin staining and microvessel density (MVD) through immunohistochemical staining. Data were processed with independent sample t test and Fisher's exact probability test. Results: (1) The times of complement skin grafting of patients in stage-Ⅱ skin grafting group was (1.83±0.17) times, which was obviously less than (3.36±0.63) times in stage-Ⅰ skin grafting group (t=2.19, P<0.05). The wound basic healing time of patients in stage-Ⅱ skin grafting group was (35.1±2.3) d, which was obviously shorter than (48.8±4.9) d in stage-Ⅰ skin grafting group (t=2.27, P<0.05). (2) Immediately after tangential excision, the intercellular substance was few between the adipose cells in adipose tissue of patients in stage-Ⅱ skin grafting group. Immediately after the removal of porcine ADM, there was regenerated granulation tissue in the intercellular space of adipose cells of adipose tissue of patients in stage-Ⅱ skin grafting group. Immediately after tangential excision, the MVD of adipose tissue of patients in stage-Ⅱ skin grafting group was 20.2±1.3 under per 400-time field, which was obviously less than 32.2±1.9 under per 400-time field immediately after the removal of porcine ADM (t=-5.38, P<0.01). Conclusions: Meek skin grafting on the adipose tissue in stage-Ⅱ surgery after tangential excision could reduce the times of complement skin grafting and shorten wound healing time of patients with extensive deep burns. The mechanism may be related to the improvement of the recipient condition of adipose tissue.

Effects of miR-221 on the apoptosis of non-small cell lung cancer cells by lncRNA HOTAIR.

OBJECTIVE: The aim of this study was to investigate the effects of miR-221 on the proliferation of non-small cell lung cancer (NSCLC) cells through long non-coding RNA (lncRNA) HOX transcript antisense RNA (HO-TAIR), and to explore the possible underlying mechanism. PATIENTS AND METHODS: Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was applied to detect the expression level of HOTAIR in 38 NSCLC patients. The correlations of HOTAIR expression with clinic-pathological features, as well as the correlation between HOTAIR expression and miR-221 expression was analyzed by RT-PCR. Furthermore, NSCLC cell lines were cultured in vitro, and the expressions of HOTAIR and miR-221 in NSCLC cells were also detected. A549 cells were transfected with miR-221 mimics, miR-221 inhibitors, HOTAIR-small interfering RNAs (siRNAs) and plasmid cytomegalovirus deoxyribonucleic acid (pcDNA)3.1-HOTAIR. The interaction between miR-221 and HOTAIR in transfected cells was analyzed via RT-PCR and Northern blotting. Ultimately, flow cytometry was adopted to analyze the effects of miR-221 on the apoptosis of NSCLC cells through HOTAIR. RESULTS: The expression of HOTAIR in tissues of clinical patients only exhibited a correlation with the stage of cancer. The expressions of HOTAIR in patients with stage I and II were remarkably lower than those with stage III and IV. Additionally, the expression of HOTAIR was negatively correlated with the expression of miR-221 (r=-0.7651, p<0.0001). Further studies revealed that there was a negatively regulatory interaction between miR-221 expression and HOTAIR expression. Apoptosis assay results manifested that miR-221 significantly promoted the apoptosis of NSCLC cells by negatively regulating HOTAIR expression. CONCLUSIONS: MiR-221 promotes the apoptosis of NSCLC cells through negative regulation of lncRNA HOTAIR, which can be used in the treatment of NSCLC.

Overexpression of lncRNA GAS5 attenuates cardiac fibrosis through regulating PTEN/MMP-2 signal pathway in mice.

OBJECTIVE: The present study aimed at investigating the effect and mechanism of lncRNA Growth Arrest-Specific 5 (GAS5) in cardiac fibrosis induced by isoproterenol (ISO) in vivo. MATERIALS AND METHODS: The C57BL/6 mice were injected subcutaneously with ISO to induce cardiac fibrosis and injected intracoronary with lentivirus pcDNA-GAS5. After 3 weeks, cardiac function was detected by echocardiography. The interstitial collagen volume was stained by Masson trichrome. The expression of GAS5 was measured by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). The expressions of phosphatase and tensin homologue (PTEN), matrix metalloprotease-2 (MMP-2), α-smooth muscle actin (α-SMA), and collagen I protein were measured by Western blot. RESULTS: Our results indicated that the expression of GAS5 was significantly down-regulated in the fibrotic myocardium. Overexpression of GAS5 after injection with pcDNA-GAS5 could attenuate cardiac fibrosis and improve cardiac function through increasing the expression of PTEN and decreasing the expression of MMP-2, α-SMA, and collagen I. CONCLUSIONS: Overexpression of GAS5 could attenuate cardiac fibrosis induced by ISO. The molecular mechanism was associated with the regulation of PTEN/MMP-2 signaling pathway.

MiR-122-3p regulates the osteogenic differentiation of mouse adipose-derived stem cells via Wnt/ß catenin signaling pathway.

OBJECTIVE: To explore the regulatory mechanism of micro-ribonucleic acid (miR)-122-3p in the osteogenic differentiation of mouse adipose-derived stem cells (mADSCs). MATERIALS AND METHODS: The regulatory mechanism of miR-122-3p in the osteogenic differentiation of mesenchymal stem cells was investigated through its overexpression and knockdown. RESULTS: The overexpression of miR-122-3p inhibited the osteogenic differentiation of mADSCs. On the contrary, its knockdown promoted the osteogenic differentiation of mADSCs. The further study on the molecular mechanism of miR-122-3p regulating mADSCs' osteogenic differentiation showed that the overexpression of miR-122-3p could activate the Wingless and int-1 (WNT)/ß-catenin signaling pathway, but the knockdown of miR-122-3p could repress this signaling pathway. CONCLUSIONS: MiR-122-3p influences the osteogenic differentiation of mADSCs by modulating the WNT/ß-catenin signaling pathway.

[Long-term outcomes of multiple arterial off-pump coronary artery bypass grafting].

Objective: To evaluate the long-term clinical outcomes of multiple arterial off-pump coronary artery bypass grafting (OPCAB) on left main coronary artery or multivessel disease. Methods: A total of 329 patients [303 males and 26 females, with a mean age of (55.1±9.1) years old] with left main coronary artery or multivessel disease who underwent isolated multiple arterial OPCAB in Ruijin Hospital between January 2006 and June 2018 were included. The baseline characteristics, perioperative and long-term outcomes were analyzed. Kaplan-Meier analysis was applied for estimation of freedom from major adverse cardiac and cerebrovascular events (MACCE) and overall survival. Independent predictors of MACCE were assessed by Cox regression analysis. Results: The perioperative mortality was only 0.9% (3/329). The median follow-up time was 65(22, 126) months, and 302 (91.8%) patients were followed up. The long-term MACCE rate, mortality, cardiac mortality, myocardial infarction (MI) rate, stroke rate and target vessel revascularization (TVR) rate were 13.9%, 4.6%, 1.3%, 3.6%, 6.0% and 6.0%, respectively. Among the alive patients, 51.3% were in New York Heart Association (NYHA) Ⅰ class and 80.9% had no recurrence of angina pectoris. The estimated 5-year and 10-year overall survival rates were 97.3% and 93.1%, respectively. The estimated 5-year and 10-year freedom from MACCE survival rates were 91.5% and 78.0%, respectively. Senility (OR=1.058, 95%CI: 1.020-1.097, P=0.002) and history of MI (OR=2.200, 95%CI: 1.131-4.412, P=0.021) were the independent risk factors for late MACCE. Conclusion: Multiple arterial OPCAB appears to be safe and with excellent clinical outcomes in treating left main coronary artery or multivessel disease.

DCA can improve the ACI-induced neurological impairment through negative regulation of Nrf2 signaling pathway.

OBJECTIVE: To investigate the effect of tauroursodeoxycholic acid (TUDCA) on neurological impairment induced by acute cerebral infarction (ACI) and its relevant mechanism of action. PATIENTS AND METHODS: A total of 60 male Sprague-Dawley (SD) rats were randomly divided into Sham group (n = 20), ACI group (n = 20), and TUDCA group (n = 20). The rat model of ACI in middle cerebral artery was established. TUDCA was intravenously injected into rats in the TUDCA group, while an equal amount of sodium bicarbonate solution was intravenously injected into the other two groups. The blood was drawn after modeling to detect the content of serum glutamate (Glu), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). The degree of cerebral infarction in each experimental group was observed under an optical microscope, and the infarct area was measured and compared. The content of serum tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and high-sensitivity C-reactive protein (hs-CRP) was detected via enzyme-linked immunosorbent assay (ELISA); mRNA and protein expressions of them were detected using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, followed by statistical analysis. Moreover, the expression levels of serum malondialdehyde (MDA), oxidized-LDL (ox-LDL), superoxide dismutase (SOD), and glutathione peroxidase (GPX) were detected, followed by statistical analysis. The protein expressions of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), very low-density lipoprotein receptor (VLDLR), nuclear factor-κB (NF-κB), B-cell lymphoma 2-associated X protein (Bax), and caspase-3 were detected via Western blotting, and the gray value was determined, followed by statistical analysis. RESULTS: TUDCA could improve the symptoms of neurological impairment in ACI patients, decrease the National Institute of Health Stroke Scale (NIHSS) score but increase the activity of daily living (ADL) score of patients, and significantly reduce the content of serum TG, TC, and LDL-C, showing statistically significant differences (p < 0.05). TUDCA significantly decreased the serum Glu content in ACI rats, reduced the cerebral infarction area and lowered the serum TG, TC, and LDL-C content, displaying statistically significant differences (p < 0 .05). Besides, TUDCA inhibited mRNA and protein expressions of TNF-α, IL-8, and hs-CRP, and alleviated the inflammatory response. TUDCA inhibited MDA and ox-LDL expressions, but increased SOD and GPX expressions, and relieved oxidative stress injury. In addition, TUDCA could negatively regulate Nrf2 signaling pathway, and down-regulated VLDLR and NF-κB protein expressions and expressions of apoptotic proteins (Bax and caspase-3). CONCLUSIONS: TUDCA can alleviate the ACI-induced neurological impairment in rats through mitigating lipid peroxidation and inflammatory response and reducing apoptosis, whose relevant mechanism may be that TUDCA negatively regulates Nrf2 signaling pathway.

MiR-374b promotes osteogenic differentiation of MSCs by degrading PTEN and promoting fracture healing.

OBJECTIVE: To investigate whether miR-374b can promote the differentiation of MSCs into osteoblasts by mediating PTEN, thus promoting fracture healing. MATERIALS AND METHODS: Primary cultured mouse mesenchymal stem cells were obtained for following experiments. Flow cytometry was used to determine the expression of MSCs surface antigens to identify the purity. Alizarin red staining was used to detect whether MSCs could differentiate into osteoblasts. QRT-PCR was used to detect the expression of osteogenic marker genes as well as miR-374b and PTEN in bone marrow-derived MSCs from fractured mice model. ALP activity detection kit was used to detect ALP activity in cells. Changes of osteogenic proteins in cells were evaluated by Western blot. Bioinformatics methods were used to predict the binding sites between miR-374 and target genes. Luciferase reporter assay was used to confirm whether miR-374 could bind to the target gene. RESULTS: Under normal culture, MSCs grew into a long fusiform shape on the 4th day. After induced in the osteogenic induction medium for seven days, calcified nodules appeared. The results of the detection of MSCs surface antigen markers showed that CD90 was 99.12%, and CD45 was 0.23%. Alizarin red staining showed that MSCs possess the ability to differentiate into osteogenic. The expression level of MiR-374b and PTEN increased significantly in the early stage of fracture in mice, but no significant difference was observed at a later stage. After overexpression of miR-374b, the cell ALP activity, the expression of osteogenesis-related genes and osteogenesis-related proteins was significantly increased, while after knocking out miR-374b, the opposite result was observed. The result of luciferase reporting assay showed that miR-374b can bind to PTEN. As mentioned above, overexpression of miR-374b resulted in upregulation of osteogenic-related genes and proteins, while over-expression of both PTEN and miR-374b could partly reverse the outcomes. CONCLUSIONS: miR-374b can promote osteogenic differentiation of MSCs by degrading PTEN, thereby promoting fracture healing.

MicroRNA-582-5p suppressed gastric cancer cell proliferation via targeting AKT3.

OBJECTIVE: To dissect the functioning mode of miR-582-5p on gastric cancer cell growth and provide therapeutic targets for gastric cancer. PATIENTS AND METHODS: Relative expression levels of miR-582-5p in human gastric cancer tissue samples and gastric cancer-derived cell lines were measured by using quantitative Real-time PCR. Cell proliferation and viability capacities were assessed by cell counting kit-8 (CCK8) assay and colony formation assay. Cell apoptosis and cell cycle distribution were identified by flow cytometry. Downstream target gene was confirmed by using luciferase and Western blotting assays. RESULTS: MiR-582-5p was downregulated in gastric cancer tissues when compared with para-carcinoma tissues (n=42). Overexpressed miR-582-5p could attenuate cell proliferation and viability capacities, as well as promoted cell apoptosis and cell cycle arrest at G0/G1 phase. AKT3 was chosen as the target gene of miR-582-5p by bioinformatics analysis and luciferase reporter assay. Moreover, restoration of AKT3 could impair tumor suppression role of miR-582-5p on gastric cancer growth. CONCLUSIONS: MiR-582-5p exerted tumor-suppressive effects on gastric cancer growth via targeting AKT3 in vitro, which provided an innovative and candidate target for diagnosis and treatment of gastric cancer.