Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective: To evaluate the difference and correlation between continuous non-invasive arterial pressure (CNAP) monitor and pulse indicated continuous cardiac output (PiCCO) monitor on determination of hemodynamic parameters in mechanically ventilated critically ill patients, and to assess the feasibility of non-invasive monitoring of hemodynamics with CNAP. Methods: A prospective observation self-control study was conducted.The critically ill patients with mechanical ventilation who needed hemodynamics monitoring, and admitted to the fourth department of intensive care unit (ICU) of Fujian Provincial Hospital from June 2018 to March 2019 were enrolled. PiCCO catheter were inserted immediately after admission, the hemodynamic indexes were measured by thermodilution method, and mean arterial pressure (MAP_PiCCO), cardiac index (CI_PiCCO), pulse pressure variation rate (PPV_PiCCO) and systemic vascular resistance index (SVRI_PiCCO) were obtained at 0 hour and 24 hours respectively. Meanwhile, the above indexes (MAP_CNAP, CI_CNAP, PPV_CNAP and SVRI_CNAP) were measured with CNAP. All measurements were repeated thrice and average values were reported. The differences in above parameters between the two methods were evaluated. Pearson test was used for the correlation analysis and Bland-Altman analysis method was used for consistency test. Results: Thirty-eight patients were enrolled into this study. One patient died within 24 hours was excluded, 2 patients were excluded due to withdrawing treatment within 24 hours, 2 patients were excluded because of atrial fibrillation, and 1 patient's data was lost due to technical problems. Thus, data from 32 patients were available for final analysis. There were 12 females and 20 males, aging 26-84 years old with the mean of (66.8±19.1) years old, body mass index (BMI) of (23.7±3.9) kg/m², acute physiology and chronic health evaluationⅡ (APACHEⅡ) score of 19.5±5.3, sepsis-related organ failure assessment (SOFA) score of 9.7±4.1. There were no significant differences in CI or PPV between CNAP and PiCCO groups [CI (mL·s^-1·m^-2): 59.8±12.6 vs. 58.5±14.2, PPV: (14.7±6.8)% vs. (14.0±6.8)%, both P > 0.05]. MAP and SVRI measured by CNAP were significantly higher than those measured by PiCCO [MAP (mmHg, 1 mmHg = 0.133 kPa): 65.6±9.4 vs. 60.1±9.2, SVRI (kPa·s·L^-1·m^-2): 206.2±53.9 vs. 179.5±57.8, both P < 0.01]. The correlation analysis showed that MAP, CI, PPV and SVRI measured by the two methods were significantly positively correlated (r value was 0.624, 0.864, 0.835 and 0.655 respectively, all P < 0.05). Bland-Altman analysis showed that CNAP and PiCCO had a good consistency for the measurement of CI and PPV, the average differences were 1.2 mL·s^-1·m^-2 and 0.5% respectively, while the 95% confidence interval (95%CI) were -12.8-15.3 mL·s^-1·m^-2 and -7.1%-8.2% respectively. However, the consistency of MAP and SVRI measured by those two methods was poor, the average differences were 5.5 mmHg and 26.8 kPa·s·L^-1·m^-2 respectively, while the 95%CI was -10.4-21.3 mmHg and -64.5-118.0 kPa·s·L^-1·m^-2 respectively. Conclusion CNAP was comparable with PiCCO when monitoring CI and PPV in mechanically ventilated critically ill patients; while the results of MAP and SVRI might be inaccurate, which should be interpreted correctly and carefully.

OBJECTIVE: To evaluate the difference and correlation between continuous non-invasive arterial pressure (CNAP) monitor and pulse indicated continuous cardiac output (PiCCO) monitor on determination of hemodynamic parameters in mechanically ventilated critically ill patients, and to assess the feasibility of non-invasive monitoring of hemodynamics with CNAP. METHODS: A prospective observation self-control study was conducted.The critically ill patients with mechanical ventilation who needed hemodynamics monitoring, and admitted to the fourth department of intensive care unit (ICU) of Fujian Provincial Hospital from June 2018 to March 2019 were enrolled. PiCCO catheter were inserted immediately after admission, the hemodynamic indexes were measured by thermodilution method, and mean arterial pressure (MAP_PiCCO), cardiac index (CI_PiCCO), pulse pressure variation rate (PPV_PiCCO) and systemic vascular resistance index (SVRI_PiCCO) were obtained at 0 hour and 24 hours respectively. Meanwhile, the above indexes (MAP_CNAP, CI_CNAP, PPV_CNAP and SVRI_CNAP) were measured with CNAP. All measurements were repeated thrice and average values were reported. The differences in above parameters between the two methods were evaluated. Pearson test was used for the correlation analysis and Bland-Altman analysis method was used for consistency test. RESULTS: Thirty-eight patients were enrolled into this study. One patient died within 24 hours was excluded, 2 patients were excluded due to withdrawing treatment within 24 hours, 2 patients were excluded because of atrial fibrillation, and 1 patient's data was lost due to technical problems. Thus, data from 32 patients were available for final analysis. There were 12 females and 20 males, aging 26-84 years old with the mean of (66.8±19.1) years old, body mass index (BMI) of (23.7±3.9) kg/m², acute physiology and chronic health evaluation II (APACHE II) score of 19.5±5.3, sepsis-related organ failure assessment (SOFA) score of 9.7±4.1. There were no significant differences in CI or PPV between CNAP and PiCCO groups [CI (mL×s^-1×m^-2): 59.8±12.6 vs. 58.5±14.2, PPV: (14.7±6.8)% vs. (14.0±6.8)%, both P > 0.05]. MAP and SVRI measured by CNAP were significantly higher than those measured by PiCCO [MAP (mmHg, 1 mmHg = 0.133 kPa): 65.6±9.4 vs. 60.1±9.2, SVRI (kPa×s×L^-1×m^-2): 206.2±53.9 vs. 179.5±57.8, both P < 0.01]. The correlation analysis showed that MAP, CI, PPV and SVRI measured by the two methods were significantly positively correlated (r value was 0.624, 0.864, 0.835 and 0.655 respectively, all P < 0.05). Bland-Altman analysis showed that CNAP and PiCCO had a good consistency for the measurement of CI and PPV, the average differences were 1.2 mL×s^-1×m^-2 and 0.5% respectively, while the 95% confidence interval (95%CI) were -12.8-15.3 mL×s^-1×m^-2 and -7.1%-8.2% respectively. However, the consistency of MAP and SVRI measured by those two methods was poor, the average differences were 5.5 mmHg and 26.8 kPa×s×L^-1×m^-2 respectively, while the 95%CI was -10.4-21.3 mmHg and -64.5-118.0 kPa×s×L^-1×m^-2 respectively. CONCLUSIONS CNAP was comparable with PiCCO when monitoring CI and PPV in mechanically ventilated critically ill patients; while the results of MAP and SVRI might be inaccurate, which should be interpreted correctly and carefully.
Adult ; Aged ; Aged, 80 and over ; Arterial Pressure ; Cardiac Output ; Critical Illness ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Prospective Studies ; Respiration, Artificial

Objective To compare volar plating and nonoperative treatment for senile comminuted fractures of the distal radius. Methods From October 2012 to June 2015, 46 senile comminuted fractures of the distal radius ( AO types B and C ) were treated surgically or conservatively. Twenty old patients were managed by open reduction and fixation with a volar locked plate. They were 7 men and 13 women, with an average age of 67. 9 ± 10. 7 years, including 7 cases of AO type 23-B and 13 cases of AO type 23-C. Twenty-six patients were managed with closed reduction and plaster cast. They were 8 men and 18 women, with an average age of 66. 2 ± 11. 5 years, including 10 cases of AO type 23-B and 16 cases of AO type 23-C. The 2 groups were compared in terms of follow-up time, union time and wrist functional scores and complica-tions. Results There was no significant difference between the 2 groups in follow-up time ( P > 0. 05 ) . Fractures in the 2 groups all united about 11 weeks after surgery. According to Dienst scoring for reduction, the volar plating group had 13 excellent cases, 4 good ones, 2 fair ones and one poor case, with an excellent to good rate of 85. 0％ while the nonoperative group had 5 excellent cases, 10 good ones, 5 fair ones and 6 poor ones, with an excellent to good rate of 57. 7％. A significant difference was shown between the 2 groups ( P <0. 05 ) . At final follow-ups, the volar plating group had significantly lower Gartland & Werley wrist functional score ( 2. 16 ± 1. 82 ) and complication rate ( 30. 0％, 6/20 ) than the nonoperative group [ 6. 62 ± 3. 78 and 53. 8％( 14/26 ) , respectively ] ( P <0. 05 ) . Conclusion In treatment of senile comminuted fractures of the distal radius, volar locked plating may lead to better functional recovery and fewer complications than nonoper-ative management. However, one should take full account of the physical condition and preference of the patient when surgery is chosen.

Objective: To explore the effect of microRNA-21 (miR-21) on myocardial fibrosis in mice with chronic viral myocarditis (CVMC) and related mechanisms. Methods: Forty 4-week-old Balb/c male mice were randomly divided into 4 groups (n=10 each): phosphate buffer saline (PBS) group, CVMC group, CVMC+miR-21 inhibitor group, CVMC+isotype control group. The first injection of Coxsackie virus B3 (CVB3) or PBS was performed on day 0, and the total study time was 42 days. Each mouse in CVMC group, CVMC+miR-21 inhibitor group and CVMC+isotype control group was intraperitoneally (i.p) injected with 100TCID50 CVB3 0.1, 0.15, and 0.2 ml on day 0, 14, and 28, respectively. The mice in PBS group were i.p injected with the same dose of PBS at the same time point. After the initial infection, each mouse in CVMC+miR-21 inhibitor group and CVMC+isotype control group was intravenously injected with 0.1 ml miR-21 inhibitor or 0.1 ml isotype control, on day 14 and 28. Cardiac function was measured on surviving mice of 4 groups by echocardiography on day 42. Then, the hearts were removed aseptically to observe the expressions of green fluorescence protein (GFP). The myocardial pathological changes were examined with HE, Masson staining and the myocardial pathological scores (PS), the collagen volume fraction (CVF) were calculated respectively. The levels of miR-21, collagen typeⅠ-A1 (COL1-A1) and collagen type Ⅲ-A1 (COL3-A1) mRNA in heart were detected by quantitative real-time polymerase chain reaction (RT-qPCR). Furthermore, the expressions of transforming growth factor-β1 (TGF-β1) and mothers against decapentaplegic homolog 7(Smad7) in heart were determined with Western blot assay. Results: (1) Cardiac function in 4 groups: Compared with PBS group, left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD) were markedly increased in CVMC group and CVMC+isotype control group (all P<0.05), whereas the left ventricular ejection fraction (LVEF) was decreased (P<0.05). LVESD and LVEDD were significantly decreased, and LVEF was increased in CVMC+miR-21 inhibitor group compared with those in CVMC group and CVMC+isotype control group (all P<0.05). (2) Myocardial pathological changes: The expressions of GFP in CVMC+miR-21 inhibitor group and CVMC+isotype control group were visible in heart tissues frozen sections. The hearts in CVMC group and CVMC+isotype control group were enlarged and stiff, inflammatory cells were visible and significantly increased myocardial fibrosis was evidenced in mice of these two groups. Higher PS and CVF were evidenced in CVMC group (PS: 1.14±0.69 vs. 0, CVF: (17.86±2.61)% vs. (5.70±1.42)%, all P<0.05) and CVMC+isotype control group(PS: 1.00±0.63 vs. 0, CVF: (16.78±2.58)% vs. (5.70±1.42)%, all P<0.05) compared to PBS group. Compared with CVMC group and CVMC+isotype control group, degree of cardiac fibrosis was reduced in mice of CVMC+miR-21 inhibitor group (CVF: (11.01±2.55)% vs. (17.86±2.61)%, (11.01±2.55)% vs. (16.78±2.58)%, all P<0.05), whereas PS were similar between them (PS: 0.89±0.60 vs. 1.14±0.69, 0.89±0.60 vs. 1.00±0.63, all P>0.05). (3) Cardiac expressions of miR-21, COL1-A1 and COL3-A1 mRNA: The cardiac expressions of miR-21, COL1-A1 mRNA, COL3-A1mRNA in CVMC group and CVMC+isotype control group were markedly higher than those in PBS group (all P<0.05), which were significantly downregulated in CVMC+miR-21 inhibitor group (all P<0.05 vs. CVMC group and CVMC+isotype control group). (4) The cardiac expressions of TGF-β1 and Smad7 protein: The cardiac expressions of TGF-β1 protein in CVMC group and CVMC+isotype control group were markedly higher, whereas the cardiac Smad7 protein expressions were significantly lower (all P<0.05) than those in PBS group (all P<0.05), these changes could be reversed in CVMC+miR-21 inhibitor group (P<0.05 vs. CVMC group and CVMC+isotype control group). Conclusions Our results suggest that miR-21 contributes to the myocardial fibrosis in CVMC mice through modulating TGF-β1/Smad7 signaling pathway.

Objective:To explore influence of position of myocardial infarction and coronary artery lesions in patients with acute ST elevation myocardial infarction (STEMI) ,and the relationship among heart failure ,arrhythmia and severity of coronary artery lesion .Methods :Clinical data of 224 patients ,who hospitalized in our hospital because of STEMI and received coronary angiography from Jan 2009 to Jun 2011 ,were retrospectively analyzed .General data of patients were collected ,and SYNTAX score was used to reflect severity of coronary artery lesion ,and the rela‐tionship among heart failure ,arrhythmia and SYNTAX scores were analyzed .Results:Incidence rate of heart fail‐ure in patients with infarction relate artery left anterior descending artery (LAD) AND/or left main coronary artery (LM) was significantly higher than that of patients with right coronary artery (RCA) (57.0% vs .39.7% , P=0.017) ,incidence rate of arrhythmia in patients with RCA was significantly higher than that of patients with left circumflex artery (LCX) (37.0% vs .6.3% , P=0.016);incidence rates of arrhythmia (48.4% ) ,shock (54.8% ) were highest in patients with inferior wall/right ventricle than those of other position , P<0.05 or <0.01.SYNTAX scores in patients with heart failure and arrhythmia were significantly higher than those of patients without heart failure and arrhythmia respectively [ (18.7 ± 9.1) scores vs .(15.4 ± 8.6) scores ,(19.7 ± 9.0) scores vs .(16.1 ± 8.8) scores , P<0.01 both] .Conclusion:Incidence rates of heart failure ,cardiogenic shock and arrhythmia are related to coronary artery lesions position and degree and myocardial infarction position in STEMI patients .

Objective To summarize the individualized cavity Single branch stent grafting through rebuilding the aortic arch surgery in 26 cases of the application of the Stanford type A aortic dissection. Methods From 2010 January to 2014 October, 26 patients received Stanford type A aortic dissection surgery, 26 patients received individualized cavity single branch stent grafting to rebuild the aortic arch surgery , together with improved myocardial protection fluid. Results In the present study, 26 cases with aortic dissection that were treated with single branch stent grafting for the reconstruction of aortic arch under DHCA and selective cerebral perfusion. Twenty-six patients received individualized cavity single branch stent grafting reconstruction of aortic arch surgery alone, and were stopped by using deep cryogenic loop (DHCA) plus selective cerebral perfusion surgical treatment. One patient suffered from permanent nerve dysfunction iand give up treatment. Conclusion The sexua branch stent grafting in reconstruction of aortic arch operation could simplify the operation procedures , shorten the operation time, and reduce the amount of blood transfusion and postoperative drainage.

Objective To evaluate the role of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) in the spinal cord in the maintenance of diabetic neuropathic pain in rats.Methods Pathogenfree male Sprague-Dawley rats,aged 2 months,weighing 180-220 g,were used in the study.Diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60mg/kg and confirmed by blood glucose ＞ 16.7 mmol/L at 72 h after STZ injection.Twenty diabetic rats were randomly allocated to diabetic neuropathic pain group (DN group,n =10) and apocynin (specific NADPH oxidase inhibitor) group (A group,n =10).Another 10 agematched normal rats served as control group (C group,n =10).Twenty-eight days after STZ injection,apyconin 5 mg/kg was injected intraperitoneally once a day for 7 consecutive days in A group.Paw withdrawal threshold to yon Frey filament stimulation (PWT) was measured before STZ injection (T1) and at 7,14,21,28 and 35 days after STZ injection (T2-6).The rats were sacrificed after PWT was measured at T6 and L4.5 segments of the spinal cord were removed for determination of NADPH oxidase subunits gp91phox and p47phox expression,MAD content and SOD activity.Results Compared with C group,PWT was significantly decreased at T3-5,gp91phox and p47phox expression was up-regulated,MAD content was increased,and SOD activity was decreased in DN and A groups.Compared with DN group,PWT was significantly increased at T6,gp91phox and p47phox expression was downregulated,MAD content was decreased,and SOD activity was increased in A group.Conclusion NADPH oxidase in the spinal cord is involved in the maintenance of diabetic neuropathic pain in rats.

ObjectiveTo establish a practical and effective clinical pathway (CP) for the etiological diagnosis of acute biliary pancreatitis.MethodsA total of 2216 patients enrolled were randomly divided into control group (n =1120) and CP group (n =1096) according to different etiological diagnosis methods including following doctor's established experiences and habits and the designed CP in our study.ResultsThere was no significant difference in baseline data between the two groups.The etiology of acute pancreatitis was determined in 91.1％ (999/1096) of cases in the CP group which was significantly higher than the control group (65.5 ％,734/1120),P ＜ 0.05.The enhanced etiological determination of CP group was mainly consisted of the increased detection of biliary stones,duodenal diseases as well as pancreas divisum,P ＜ 0.05.The positive etiological determination of magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography in the CP group were 59.1％ (273/462) and 86.0％ (98/114),respectively.ConclusionsThe CP established in this study significantly enhances the biliary etiological determination of acute pancreatitis. It is easy to be conducted and may be of importance to improve the quality of etiological diagnosis of acute pancreatitis.

Objective To study how to improve velopharyngeal ring ligafion procedure by using ring ligator in velopharyngeal ring ligatian procedure and settle the problem that there is no standard to measure the interspace of the cavity of pharynx.Methods Select some deft palate patients who were between 3 to 17 ages.Then made five groups according to age (3 to 5,6 to 8,9 to 11,12 to 14,15 to 17).Then made five different types of ring ligators accrding to the normal size of the cavity of pharynx of different ages.Results The ring ligators were easily used and all the patients were repaired satisfied.Conclusion The application of ring ligator in velopharyngeal ring ligation procedure is simple and feasible.