Ocular surface changes in keratoconus after long-term wearing of rigid gas permeable contact lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze changes in the ocular surface parameters of keratoconus after long-term wearing of rigid gas permeable contact lens(RGPCL).METHODS:Prospective case study. A total of 113 keratoconus patients(213 eyes)fitted with RGPCL in the optometry center of Gansu Provincial Hospital from January 2018 to January 2022 were included. They were divided into three groups according to the severity of keratoconus, including 42 cases(80 eyes)in mild keratoconus group, 54 cases(102 eyes)in moderate keratoconus group and 17 cases(31 eyes)in severe keratoconus group. Furthermore, the non-invasive tear break-up time(NIBUT), non-invasive tear meniscus height(NITMH), red eye index, lipid layer thickness, fluorescent corneal staining, meibomian gland secretory function, Schirmer I test and ocular surface disease index(OSDI)scores were observed by Keratograph analyzer before and after wearing RGPCL for 1 wk, 1, 3, 6, 12 mo, respectively.RESULTS: There were no statistical significance in the age, NIBUT, NITMH, lipid layer thickness, meibomian gland secretory function and Schirmer I test among the three groups(P>0.05), while there were statistical significance in the sphere, cylinder, spherical equivalent, best corrected visual acuity(BCVA), non-contact intraocular pressure(IOPNCT), anterior, posterior corneal surface Kmax, corneal surface thickness at the thinnest point, eye redness index, fluorescent corneal staining, and OSDI(P<0.05). In the mild keratoconus group, NIBUT had statistical differences at 3, 6 and 12 mo after wearing RGPCL(P<0.05), NITMH had statistical differences in 6 and 12 mo(P<0.05), the eye redness index, fluorescent corneal staining and OSDI scores had statistical differences in 1 wk and 1 mo(P<0.05), and lipid layer thickness and meibomian gland secretory function had statistical differences in 12 mo(P<0.05). In the moderate keratoconus group, there were statistical differences in NIBUT at 6 and 12 mo after wearing lenses(P<0.05); there were statistical differences in the NITMH, lipid layer thickness and meibomian secretory function at 12 mo after wearing lens(P<0.05); there were statistical differences in the eye redness index at 1 wk, 1 and 3 mo after wearing RGPCL(P<0.05); there were statistical differences in the fluorescent corneal staining at 1 wk after wearing RGPCL(P<0.05); there were statistical differences in the OSDI at 1 wk and 1 mo after wearing RGPCL(P<0.05). In the severe keratoconus group, there were statistical differences in the NIBUT, NITMH and eye redness index at 1 wk, 1, 3, 6 and 12 mo after wearing RGPCL(P<0.05); there were statistical differences in the lipid layer thickness at 6,12 mo after wearing RGPCL(P<0.05); there were statistical differences in the fluorescent corneal staining and OSDI scores at 1 wk, 6 and 12 mo after wearing RGPCL(P<0.05); there were statistical differences in the meibomian secretory function at 6 and 12 mo after wearing RGPCL(P<0.05); and there were statistical differences in the Schirmer I test at 12 mo after wearing RGPCL(P<0.05).CONCLUSION: Long-term wearing of RGPCL can affect the ocular surface microcirculation in keratoconus patients, thus making differences in patients subjective. However, it has no significant impact on the visual quality of patients. Therefore, long-term wearing of RGPCL is safely to control the progression of keratoconus.

Analysis of factors associated with anxiety symptoms of high school students in Inner Mongolia / 中国学校卫生

Objective@#To analyse the correlation between unhealthy lifestyles and anxiety symptoms among high school students in Inner Mongolia Region, so as to provide a scientific basis for the prevention of anxiety symptoms among high school students.@*Methods@#From September to November 2023, 35 362 high school students were selected by stratified cluster random sampling method from 12 cities (103 counties) in Inner Mongolia Region, and the survey was conducted by using the questionnaire on student health status and influencing factors. The χ2 test and multivariate Logistic regression analyses were used to determine the influencing factors of anxiety symptoms.@*Results@#The total number of students with anxiety symptoms was 2 747, and the detection rate of anxiety symptoms was 7.77%. The results of multivariate Logistic regression analyses showed that female students, father having higher education background, never eating breakfast, being overweight and obese, sleeping <8 h/d, being scolded by parents in the past 30 days, and depressive symptoms were positively correlated with the anxiety symptoms of the high school students (OR=1.31, 1.23, 1.53, 1.14, 1.22, 1.51,28.92); nonsmoking, having no alcohol consumption, no Internet addiction and no use of sedatives without doctors permission were all negatively correlated with anxiety symptoms of high school students (OR=0.84, 0.73, 0.57,0.40) (P<0.05).@*Conclusions@#Anxiety symptoms of high school students are closely related to unhealthy lifestyle. Measures should be taken to improve unhealthy lifestyle, so as to reduce the occurrence of anxiety symptoms in high school students.

Effect of pulsed electric field on reactive oxygen species generation in pancreatic cancer cells / 中华肝胆外科杂志

Objective:To investigate the changes of reactive oxygen species (ROS) in pancreatic cancer cells under the effect of pulsed electric fields (PEF).Methods:Murine-derived pancreatic cancer cells Panc02 were treated with PEF at electric field strengths of 0, 250, 500, 750, and 1 000 V/cm, respectively. The intracellular ROS generation patterns under the different field strengths and at different times after the PEF were investigated in vitro by flow cytometry and immunofluorescence, meanwhile exploring the apoptosis of murine and human pancreatic cancer cells under different field strengths. Twenty 6- to 8-week-old male C57BL/6 SPF mice were prepared as orthotopic pancreatic cancer models and divided into five groups of four mice each: 250 V/cm PEF group, 500 V/cm PEF group, 750 V/cm PEF group, 1 000 V/cm PEF group, and sham operation group. ROS expression in the residual tumor tissues of mice in each group was detected by immunofluorescence.Results:Under the 500 V/cm, 750 V/cm and 1 000 V/cm electric field strength, the proportion of cells with intracellular ROS expression was decreased after 6 h, 12 h, 24 h and 48 h of the PEF compared with 2 h after the PEF, and the differences were statistically significant (all P<0.05). Compared with 0 V/cm PEF group, ROS expression increased in Panc02 cells treated with 500 V/cm and 750 V/cm PEF groups, and the differences were statistically significant (all P<0.05). Compared with 250 V/cm PEF group under the same time, ROS in Panc02 cells treated with 500 V/cm and 750 V/cm electric field strengths increased, and the differences were statistically significant (all P<0.05). The proportions of apoptosis of both Panc02 cells and MIA-PaCa-2 cells increased with rising field strength and peaked at the field strength of 750 V/cm. Compared with the sham-operated group, the expression of ROS was increased in pancreatic cancer tissues of mice in the 500 V/cm PEF-treated group (16.65±6.01 vs. 2.38±1.21, t=-6.53) and 750 V/cm PEF-treated group (16.54±4.41 vs. 2.38±1.21, t=-6.48), and the differences were statistically significant in both cases (both P<0.001). Conclusion:PEF treatment was able to increase the level of ROS in both pancreatic cancer cells and tissues, and more ROS were produced when the electric field strength was 500 and 750 V/cm.

Effects of nucleus accumbens GABA-lateral hypothalamic area MCH neural pathway on rewarding feeding / 中华行为医学与脑科学杂志

Objective:To explore the effects of the γ-aminobutyric acid(GABA) neurons and melanin-concentrating hormone (MCH) neurons of the nucleus accumbens (NAc)-lateral hypothalamic area (LHA) neural pathway on the rewarding feeding(palatable food sweat condensed milk) in the obesity rats.Methods:Total 142 male Wistar rats of SPF grade were divided into normal diet (ND) group ( n=68) and high-fat diet induced obesity (DIO) group ( n=74) according to the principle of body mass matching. The rats in the two groups were given normal diet and high-fat diet for 8 weeks. Eight weeks later, 6 DIO rats were randomly selected to observe the nerve projection from GABA neurons in NAc to MCH neurons in LHA by fluorogold retrograde tracing combined fluorescence immunohistochemistry. And the expressions of c-Fos and MCH in LHA after ingestion of sweet condensed milk(rewarding feeding) were observed by fluorescence immunohistochemistry (6 rats in each group). GABA receptor agonist Musimol or GABA receptor antagonist Bicuculine was microinjected into the nucleus of LHA to observe the effect of GABA on rewarding food intake in ND and DIO rats ( n=8 in each group), and the changes of rewarding food intake after blocking MCH signal ( n=8 in each group). SPSS 17.0 was used for statistical analysis, two-way ANOVA and post hoc Bonferroni test were used for comparison among multiple groups, and t-test was used for comparison between two groups. Results:After 8 weeks of high-fat diet modeling, the intake of delicious food in DIO rats was significantly higher than that in ND rats((12.52±2.29) mL, (7.45±1.23) mL, t=4.778, P<0.01) after satiety.The results of fluorogold retrograde tracing combined with fluorescence immunohistochemistry showed that GABA neurons in NAc projected nerve fibers to neurons in LHA, and GABA A receptors in some neurons in LHA coexisted with MCH.The results of NAc-LHA pathway on delicious food intake showed that the interaction between rat group and drug intervention was significant( F=9.869, P<0.01). Simple effect analysis showed that the intake of delicious food after microinjection of Musimol into LHA nucleus of ND rats was significantly lower than that of microinjection normal saline ((4.25±1.38) mL, (7.29±1.49) mL, P<0.01), while the intake of delicious food after injection of Bicuculine was significantly higher than that of microinjection normal saline((10.72±2.11) mL, (7.29±1.49) mL, P<0.05). The intake of delicious food after microinjection of Musimol into LHA nucleus in DIO group was significantly lower than that of microinjection normal saline((3.51±1.77)mL, (13.68±2.95) mL, P<0.01), but there was no significant difference between microinjection Bicuculine and microinjection normal saline ((14.83±3.44) mL, (13.68±2.95) mL, P>0.05). The results of blocking MCH signal on delicious food intake showed that the interaction effect between SNAP-94847 and Bicuculine intervention was not significant ( F=1.468, P>0.05). The main effect of SNAP-94847 intervention was significant ( F=15.880, P<0.01)and the main effect of Bicuculine intervention was significant ( F=6.930, P<0.05). After intracerebroventricular injection of MCH receptor blocker SNAP-94847, the delicious food intake of ND rats was significantly less than that of injection normal saline((4.78±1.72) mL, (7.63±2.77) mL, P<0.05), and it was not affected by pre injection of Bicuculine in LHA ((6.24±2.18) mL, (4.78±1.72) mL, P>0.05). In the DIO rats, the interaction effect between SNAP-94847 and Bicuculine intervention was not significant( F=0.006, P>0.05). The main effect of SNAP-94847 intervention was significant ( F=18.46, P<0.01) and the main effect of Bicuculine intervention was not significant ( F=2.059, P>0.05). After intracerebroventricular injection of MCH receptor blocker SNAP-94847, the delicious food intake of DIO rats was significantly lower than that of injection normal saline((6.89±2.11) mL, (12.19±4.36) mL, P<0.05), and it was not affected by pre injection of Bicuculine in LHA ((8.72±2.26) mL, (6.89±2.11) mL, P>0.05). Conclusion:GABAergic signal in NAc can regulate the expression of MCH in neurons of LHA. In the DIO rats, the sensitivity of MCH neurons in LHA to satiety signal decreases and the hedonic feeding increases.

Regulatory effect of edaravone on the photoreceptor autophagy at the early stage of experimental retinal detachment in rats / 中华实验眼科杂志

Objective:To investigate the effect of edaravone, a free radical scavenger, on the regulation of retinal autophagy and the protection of photoreceptor cells at the early stage of experimental retinal detachment (RD) in rats.Methods:Fifty-one adult male Sprague-Dawley rats were used for RD model establishment, and another 24 rats were served as PBS injection group.The RD model was established via subretinal injection of 0.5% sodium hyaluronate into the right eye of the rats and the rats with successful modeling were randomly divided into RD model group and edaravone treatment group.The rats in the edaravone treatment group were given edaravone of 3 mg/kg intraperitoneally, twice a day after modeling, and the rats in the PBS injection group and RD model group were given equal volume of normal saline.Rats were sacrificed on the 1st day, 3rd day and 7th day following modeling.The T-superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) content in the intraocular fluid was detected.The expression levels of superoxide dismutase 2 (SOD2), nuclear factor E2-related factor 2 (Nrf2), autophagy related gene 4 (Atg4), microtubule-associated protein 1 light chain 3B (LC3B) and other proteins in retinal tissue were identified by Western blot analysis.TUNEL staining was performed on paraffin sections of the whole eyeball to analyze the apoptosis of photoreceptor cells.The study protocol was approved by an Ethics Committee of Xi'an Fourth Hospital (No. 2016016). The use and care of animals complied with the Regulations on the Administration of Experimental Animals.Results:The RD area was more than 60% in rat eyes of RD model.There were significant differences in MDA content and T-SOD activity among different groups at various time points (MDA: Fgroup=385.513, P<0.01; Ftime=13.021, P<0.01.T-SOD: Fgroup=48.865, P<0.01; Ftime=7.700, P=0.003). Compared with the PBS injection group, the MDA concentration was significantly increased and the T-SOD activity was significantly decreased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05). The MDA concentration was significantly reduced and the T-SOD activity was significantly elevated in the edaravone treatment group on the 1st, 3rd and 7th day after modeling in comparison with those of the RD group (all at P<0.05). Compared with the PBS injection group, the relative expression levels of SOD2 and Nrf2 proteins were significantly increased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased on the 1st, 3rd and 7th day after modeling (all at P<0.05). The expression level of SOD2 in the edaravone treatment group was significantly higher than that in the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and the expression level of Nrf2 was significantly increased in the edaravone treatment group on the 1st and 3rd day after modeling compared with that of the RD group (both at P<0.05), and the expression levels of Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased in the edaravone treatment group on the 3rd day after modeling in comparison with those of the RD group (both at P<0.05). No significant TUNEL positive cells were observed in PBS injection group at all time points, and TUNEL positive cells were observed on the 1st, 3rd and 7th day after modeling in the RD group, and the expression level of caspase-3 in the RD group was significantly increased in comparison with that of the PBS injection group ( P<0.05). The apoptosis of photoreceptor cells and the expression level of caspase-3 in edaravone treatment group were significantly decreased in comparison with those of the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05). Conclusions:The intraperitoneal injection of edaravone, twice a day, can significantly improve the antioxidant capacity of the retina after experimental RD in rats, regulate retinal autophagy and reduce the apoptosis of photoreceptor cells in early-stage RD.

Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

Viruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of CbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, CbAE-2 presented low toxicity in vivo and in vitro, highlighting its potential as a broad-spectrum antiviral drug.

Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy

Coronavirus disease 2019 (COVID-19) threatens global public health and economy. In order to develop safe and effective vaccines, suitable animal models must be established. Here we report the rapid adaption of SARS-CoV-2 in BALB/c mice, based on which a convenient, economical and effective animal model was developed. Specifically, we found that mouse-adapted SARS-CoV-2 at passage 6 (MACSp6) efficiently infected both aged and young wild-type BALB/c mice, resulting in moderate pneumonia as well as inflammatory responses. The elevated infectivity of MACSp6 in mice could be attributed to the substitution of a key residue (N501Y) in the receptorbinding domain (RBD). Using this novel animal model, we further evaluated the in vivo protective efficacy of an RBD-based SARS-CoV-2 subunit vaccine, which elicited highly potent neutralizing antibodies and conferred full protection against SARS-CoV-2 MACSp6 challenge. This novel mouse model is convenient and effective in evaluating the in vivo protective efficacy of SARS-CoV-2 vaccine. SummaryThis study describes a unique mouse model for SARS-CoV-2 infection and confirms protective efficacy of a SARS-CoV-2 RBD subunit vaccine.

Clinical study of ultrasound evaluation of fiberoptic bronchoscope guided tracheotomy / 中华危重病急救医学

Objective:To explore the clinical effect of ultrasound evaluation of fiberoptic bronchoscope (FB) guided tracheotomy, which can provide help for difficult tracheotomy and new operators.Methods:The operating protocol was standardized for ultrasound evaluation of FB guided tracheotomy. Ten patients with difficult tracheotomy admitted to the department of critical care medicine of Donge Hospital from October 2019 to January 2020 were enrolled. According to this protocol, FB guided tracheotomy was performed under the ultrasound evaluation, and the amount of blood loss, operation time and related complications during procedures were collected.Results:The preparation of supplies, personnel, patients and the operation, the process of FB guided tracheotomy under the ultrasound evaluation were standardized. When tracheotomy was preformed for patients with difficult tracheotomy, it was necessary to use ultrasound first to evaluate the neck condition and vascular disorientation of patients, and the tracheotomy plan (tracheotomy site, incision size, and incision depth) was designed, and then the tracheotomy process was monitored under the guidance of FB. Among the 10 patients with difficult tracheotomy, 6 were male and 4 were female; body mass index was (32.2±1.4) kg/m 2. Tracheotomy was successfully completed within 10 minutes in all the 10 patients, with less than 5 mL blood loss, and no complications occurred. Conclusion:Ultrasound evaluation of FB guided tracheotomy can improve the clinical operations and ensure patient safety.

Effects of LHA-NAc orexinergic pathway on gastric motility and reward feeding in rats / 中华行为医学与脑科学杂志

Objective:To investigate the regulation of orexinergic pathway from the lateral hypothalamic area (LHA) to the nucleus accumbens (NAc) on gastric function and reward feeding.Methods:(1)Forty-eight rats were randomly selected and divided into six groups: normal saline (NS) group, 1 μg orexin-A group, 5 μg orexin-A group, 10 μg orexin-A group, 20 μg orexin receptor antagonist (SB334867) group, 20 μg SB334867 + 5 μg orexin-A group with eight in each group according to the random number table. The gastric motility of rats was observed by injecting orexin-A and SB334867 into NAc. (2)Thirty-two rats were randomly selected and divided into four groups according to the random number table, with eight in each group. They were divided into NS + sham stimulation (SS) group, NS + electrical stimulation (ES) group, SB334867(20 μg) + SS group, and SB334867(20 μg) + ES group. The gastric motility of rats were observed by electro-stimulation of rat LHA and rat NAc injection of SB334867. (3)In order to observe the feeding-behavior related conditioned place preference (CPP) and gastric function (such as gastric emptying and gastric secretion), thirty-two rats were randomly divided into four groups with eight in each group by using the method of NAc injection of orexin-A and SB334867 according to the random number table: NS group, orexin-A(5 μg), SB334867(20 μg), SB334867(20 μg) + orexin-A(5 μg). (4)Thirty-two rats were randomly selected in accordance with the random number table and divided into four groups with eight in each group: NS + SS group, NS + ES group, SB334867(20 μg) + SS group, SB334867(20 μg) + ES group, using electro-stimulation of rat LHA and rat NAc injection of SB334867, observing the feeding-behavior related CPP and gastric function (such as gastric emptying and gastric secretion).Results:(1)In the gastric motility experiment, both the NAc microinjection of orexin-A and electrical stimulation of the LHA significantly increased the amplitudes and frequencies of gastric contraction in rats, and these effects could be blocked by the pre-administration of SB334867 (10 min after administration of orexin-A: 10 μg orexin-A group (60.78±5.67)% vs NS group (7.35±1.08)%; t=26.18, P<0.05). (2)The results of gastric emptying showed that the rates of gastric emptying were significantly increased by the NAc microinjection of orexin-A and electrical stimulation of LHA, which were blocked by the SB334867 pretreatment (after electrical stimulation of LHA: NS + SS group (71.18±17.78)% vs NS+ ES group (132.23±31.18)%; t=4.81, P<0.05). (3)Orexin-A microinjection in the NAc and electrical stimulation of the LHA significantly increased gastric acid secretion, and these effects could be blocked by pre-injection of SB334867 in NAc (90 minutes after administration of orexin-A: orexin-A group(100.18±23.23) vs NS group (39.23±7.69); t=7.05, P< 0.05) in the gastric secretion experiment.(4)The results of CPP showed that the rats were kept in the chocolate compartment for a longer time after the NAc microinjection of orexin-A and electrical stimulation of the LHA, which could be blocked by the SB334867 pretreatment in NAc (after LHA was electrically stimulated: NS+ SS group (36.23±6.23)% vs NS+ ES group (53.36±6.66)%; t=5.31, P<0.05). Conclusion:There is an orexinergic pathway from LHA to NAc that may regulate gastric function and food reward.

Effects of Wenxin granules and bisoprolol fumarate combined with aerobic exercise on serum matrix metallo-proteinase -1 and N - terminal pro - brain natriuretic peptide levels in patients with unstable angina pectoris / 中国基层医药

Objective To investigate the influence of Wenxin granules and bisoprolol fumarate combined with aerobic exercise on serum matrix metalloproteinase -1(MMP -1) and N - terminal pro - brain natriuretic peptide (NT - proBNP) levels in patients with unstable angina pectoris. Methods From January 2016 to February 2018, 92 patients with unstable angina pectoris in Lishui Hospital of Traditional Chinese Medicine were selected and randomly divided into control group(n = 46) and study group(n = 46) according to the digital table. On the basis of routine intervention,the control group was given bisoprolol fumarate for 2 weeks and aerobic exercise for 1 month, while the study group was given bisoprolol fumarate,aerobic exercise and Wenxin granules for 2 weeks. The frequency and duration of angina pectoris before and after 1 month of treatment,clinical efficacy,serum MMP -1 and NT - proBNP levels,blood rheology index(plasma viscosity,whole blood high shear viscosity,total blood low - cut viscosity,fibrinogen) and incidence of adverse reactions were observed. Results After 1 month of treatment,the frequency of angina pectoris was lower than that before treatment,and the duration was shorter than that before treatment,which in the study group [(2. 09 ± 0. 65)times/ week,(2. 24 ± 0. 83)min/ time] were better than those in the control group(t1 = 10. 898,t2 =9. 302,all P < 0. 05). The total effective rate of the study group(91. 30％ ) was higher than that of the control group (73. 91％ )(χ2 = 4. 842,P < 0. 05). After 1 month of treatment,the serum levels of MMP - 1 and NT - proBNP in the two groups were lower than those before treatment,which in the study group[(196. 10 ± 55. 01) g/ L,(403. 82 ± 114. 15)ng/ L] were lower than those in the control group ( t1 = 3. 619, t2 = 4. 185, P < 0. 05). At the end of treatment,the plasma viscosity,whole blood high - viscosity,whole blood low - cut viscosity,fibrinogen level in the two groups were lower than those before treatment,which in the study group were lower than those in the control group(all P < 0. 05). The incidence rate of adverse reactions in the study group was 15. 22％ ,which in the control group was 10. 87％ ,there was no statistically significant difference between the two groups (χ2 = 0. 383,P > 0. 05). Conclusion The combination of Wenxin granules, bisoprolol fumarate and aerobic exercise for patients with unstable angina pectoris not only can reduce the frequency of angina pectoris,MMP - 1 and NT - proBNP levels,but also can improve the treatment of disease. Besides,it does not increase the risk of adverse reactions.

Effects of Wenxin granules and bisoprolol fumarate combined with aerobic exercise on serum matrix metallo-proteinase-1 and N-terminal pro-brain natriuretic peptide levels in patients with unstable angina pectoris / 中国基层医药

Objective To investigate the influence of Wenxin granules and bisoprolol fumarate combined with aerobic exercise on serum matrix metalloproteinase－1(MMP－1) and N－terminal pro－brain natriuretic peptide (NT－proBNP) levels in patients with unstable angina pectoris.Methods From January 2016 to February 2018, 92 patients with unstable angina pectoris in Lishui Hospital of Traditional Chinese Medicine were selected and randomly divided into control group(n=46) and study group(n=46) according to the digital table.On the basis of routine intervention,the control group was given bisoprolol fumarate for 2 weeks and aerobic exercise for 1 month, while the study group was given bisoprolol fumarate,aerobic exercise and Wenxin granules for 2 weeks.The frequency and duration of angina pectoris before and after 1 month of treatment,clinical efficacy,serum MMP－1 and NT－proBNP levels,blood rheology index(plasma viscosity,whole blood high shear viscosity,total blood low－cut viscosity,fibrinogen) and incidence of adverse reactions were observed.Results After 1 month of treatment,the frequency of angina pectoris was lower than that before treatment,and the duration was shorter than that before treatment,which in the study group [(2.09 ± 0.65)times/week,(2.24 ± 0.83)min/time] were better than those in the control group(t1=10.898,t2= 9.302,all P<0.05).The total effective rate of the study group(91.30% ) was higher than that of the control group (73.91% )(χ2 =4.842,P<0.05).After 1 month of treatment,the serum levels of MMP－1 and NT－proBNP in the two groups were lower than those before treatment,which in the study group [(196.10 ± 55.01) g/L,(403.82 ± 114.15)ng/L] were lower than those in the control group ( t1 =3. 619, t2 =4. 185, P <0. 05 ). At the end of treatment,the plasma viscosity,whole blood high－viscosity,whole blood low－cut viscosity,fibrinogen level in the two groups were lower than those before treatment,which in the study group were lower than those in the control group(all P<0.05).The incidence rate of adverse reactions in the study group was 15.22% ,which in the control group was 10.87% ,there was no statistically significant difference between the two groups (χ2 =0.383,P>0.05).Conclusion The combination of Wenxin granules, bisoprolol fumarate and aerobic exercise for patients with unstable angina pectoris not only can reduce the frequency of angina pectoris,MMP－1 and NT－proBNP levels,but also can improve the treatment of disease.Besides,it does not increase the risk of adverse reactions.

Study on the mechanism of microRNA-210 regulating the immune pathogenesis of Treg cells in pre-eclampsia / 中国医师杂志

Objective The aim of this study was to evaluate the number of Treg cells in preeclamp-sia (PE) patients, to explore the expression levels of microRNA-210 (microRNA-210) and forkhead box p3 (Foxp3) genes in preeclampsia, and to reveal the regulatory mechanism of microRNA-210 and Foxp3 in preeclampsia. Methods Serum levels of cytokines [ interleukin ( IL)-6, IL-10, IL-17, and transforming growth factor-beta 1 (TGF-β1)] were detected with enzyme-linked immunosorbent assay (ELISA). 29 pa-tients with late-onset preeclampsia (≥36 weeks of gestation) , 27 pregnant women with normal uncomplicat-ed pregnancies (≥36 weeks of gestation) and 20 healthy non-pregnant women were enrolled in the study. Reverse-transcription polymerase chain reaction ( qRT-PCR) was performed to detect mRNA expression for maternal placenta retinoic acid-related orphan receptor C (RORc), Foxp3, and miR-210. Foxp3 protein expression was evaluated by Western blot. Results ⑴The serum levels of IL-6, IL-17 and TGF-beta 1 in preeclampsia patients were significantly higher than those in normal pregnant women, and the level of Treg cytokine IL-10 was lower than that in normal pregnant women ( P <0. 05 ) . ⑵ The percentage of CD4 +CD25 +CD127 - /CD4 +T cells in peripheral blood of preeclampsia patients was significantly lower than that of normal pregnancy group and healthy non-pregnant women ( P <0. 001 ) . ⑶ The mRNA expression of Foxp3 in placenta of preeclampsia patients was significantly lower than that of normal pregnant women, RORc in preeclampsia patients was significantly higher than that of normal pregnant women, and the expres-sion of microRNA210 in preeclampsia patients was enhanced ( P<0. 01 ) . ⑷ Consistent with mRNA ex-pression results, lower protein expression levels of Foxp3 was observed in patients with PE compared with normal pregnant subjects. Conclusions Treg cells decreased in preeclampsia patients and Treg/Th17 im-balance existed in preeclampsia patients, which regulate maternal immune tolerance to fetuses. The expres-sion of Foxp3 in placenta of preeclampsia patients was significantly decreased, which was correlated with the expression of microRNA-210.

Study on the polymorphism of PPAR-γgene and preeclampsia susceptibility / 中国医师杂志

Objective To investigate the correlation between peroxisome proliferator-activated re-ceptor-gamma ( PPAR-γ) gene polymorphism and preeclampsia ( PE) . Methods 110 PE patients and 110 normal pregnants who delivered in our hospital from May 2016 to October 2018 were selected as the study subjects. Detection of two loci of PPAR-γ gene by SNaPshot technique: rs10865710 and rs4684847. Re-sults ⑴ rs10865710:The genotype frequencies of CC, CG and GG in the control group were 44. 55％, 42. 73％ and 12. 73％, respectively, and those in the PE group were 31. 82％, 44. 55％ and 23. 64％, re-spectively. There was a critical difference in the distribution of genotype frequencies between the two groups (x2 =5. 975, P=0. 050); The frequencies of C and G alleles were 65. 91％ and 34. 09％ in the control group, 54. 09％ and 45. 91％ in the PE group, respectively. There was significant difference in the fre-quency distribution of C and G alleles between the two groups (x2 =6. 402, P=0. 015). ⑵ rs4684847:the genotype frequencies of CC, CT and TT in control group were 94. 55％, 5. 45％, 0, and those in PE group were 84. 55％, 15. 45％ and 0, respectively,with significant difference in the distribution of genotype frequencies between the two groups (x2 =5. 875, P =0. 015). The frequencies of C and T alleles in control group were 97. 27%, 2. 73% and those in PE group were 92. 27% and 7. 73%, respectively,with significant difference in allele frequency distribution between the two groups (x2 = 5. 551, P = 0. 030). ⑶ The frequency of GG genotype and G allele at rs10865710 locus in PE group was significantly higher than that in control group [OR (95% CI) =2. 600 (1. 190 - 5. 679), P = 0. 021; OR (95% CI) = 1. 64 (1. 117 -2. 411), P =0. 015]. The frequencies of CT genotype and T allele at rs4684847 locus in PE group were significantly higher than those in control group [OR (95% CI) =3. 168 (1. 199 -8. 374), P =0. 026; OR (95% CI) =2. 987 (1. 155 -7. 726), P =0. 030]. Conclusions The single nucleotide polymorphisms of PPAR-γ gene rs10865710 and rs4684847 may be related to the susceptibility to preeclampsia in Chinese population.

Decreased Expression of TRPV4 Channels in HEI-OC1 Cells Induced by High Glucose Is Associated with Hearing Impairment

PURPOSE: Previous reports have shown that hyperglycemia-induced inhibition of transient receptor potential vanilloid sub type 4 (TRPV4), a transient receptor potential ion channel, affects the severity of hearing impairment (HI). In this study, we explored the role of TRPV4 in HI using HEI-OC1 cells exposed to high glucose (HG). MATERIALS AND METHODS: HEI-OC1 cells were cultured in a HG environment (25 mM D-glucose) for 48 hours, and qRT-PCR and Western blotting were used to analyze the expression of TRPV4 at the mRNA and protein level. TRPV4 agonist (GSK1016790A) or antagonist (HC-067047) in cultured HEI-OC1 cells was used to obtain abnormal TRPV4 expression. Functional TRPV4 activity was assessed in cultured HEI-OC1 cells using the MTT assay and a cell death detection ELISA. RESULTS: TRPV4 agonists exerted protective effects against HG-induced HI, as evidenced by increased MTT levels and inhibition of apoptosis in HEI-OC1 cells. TRPV4 overexpression significantly increased protein levels of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), while TRPV4 antagonists had the opposite effect. Our results indicated that TRPV4 is a hyperglycemia-related factor that can inhibit cell proliferation and promote cell apoptosis by activating the MAPK signaling pathway in HEI-OC1 cells. CONCLUSION: Our results show that the overexpression of TRPV4 can attenuate cell death in HEI-OC1 cells exposed to HG.

Management of pregnancy in patients with complex congenital heart disease / 中国医师杂志

In recent years,with the continuous improvement of the diagnosis and treatment of congenital heart disease,most women with congenital heart disease can reach the childbearing age.For women with complex congenital heart disease,pregnancy can seriously endanger the safety of mother and baby.Therefore,pre-pregnancy assessment and standardized obstetric management of such patients are essential.

Effect of minocycline on development of diabetic neuropathic pain in rats / 中华神经医学杂志

Objective To investigate the effect of minocycline on development of diabetic neuropathic pain in rats and its mechanism.Methods Forty male Sprague-Dawley rats aged 6-8 weeks,weighting 180-220 g,were randomly assigned into 4 groups,with 10 rats in each group:normal control group (group C),normal+minocycline group (group C+M),diabetes mellitus group (group DM),diabetes+minocycline group (group DM+M).Diabetes models of rats in group DM and group DM+M were established by single intraperitoneal injection of streptozotocin (STZ,65 mg/kg),and equal volume of normal saline was injected instead of STZ into group C and group C+M;the fasting blood glucose level was tested every week,and the rats of blood glucose level ≥ 16.6 mmol/L were selected otherwise by additional injection of STZ.Two weeks after that,the intervention treatment of rats was given by single intraperitoneal injection ofminocycline (40 mg/kg) in group DM+M and group C+M.The thermal tail flick latency (TFL),thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were detected one day prior to the injection of STZ (T0),and one (T1),2 (T2),4 (T3) and 8 (T4) weeks after the injection of STZ.Eight weeks after that,the expressions of malondialdehyde (MDA) and superoxide dismutase (SOD) in the spinal dorsal ofthe rats were detected by principles ofphysical chemistry with enzyme standard instrument,and apoptotic cells in dorsal hom was detected by immunohistochemistry.Results As compared with those in group C and group C+M,TFL,TWL and MWT in group DM and group DM+M were significantly decreased at T2,T3 and T4 (P＜0.05);TFL,TWL and MWT in group DM+M were significantly increased as compared with those in group DM,reaching their peak levels at T4,with significant differences (P＜0.05).SOD level in group D and group DM was significantly lower than that in group C (P＜0.05),and MDA level in group D and group DM was significantly higher than that in group C (P＜0.05);as compared with group DM,group DM+M had higher SOD level and lower MDA level,with significant differences (P＜0.05).The number of apoptotic cells in spinal dorsal of the rats in group DM was significantly larger than that in group C (P＜0.05).Conclusion Minocycline can relieve diabetic neuropathy pain,and the underlying of mechanisms may be through anti-inflammatory,anti-oxidant stress,anti-apoptosis,and reducing the microglia activation in the spinal cord.

Construction and characterization of recombinant pseudovirus particles carrying specific genomic RNA of St.Louis encephalitis virus / 军事医学

Objective To prepare quality control samples for St.Louis encephalitis virus(SLEV)molecular detection by constructing pseudovirus containing target sequences of SLEV.Methods According to the principles of armored RNA technique, the prM gene sequence of SLEV was cloned into the prokaryotic expression vector to generate recombinant plasmid pSE380-MS2-SLEV.Then, recombinant E.coli transformed with the corresponding plasmid was induced with IPTG to produce recombinant pseudovirus particles.The particles were purified by chloroform and further characterized by double enzyme digestion and transmission electron microscopy.The temperature sensitivity experiments and quantitative RT-PCR were performed to validate the potential of these pseudovirus particles as quality control samples.Results PCR amplification and sequencing analysis confirmed that the prM gene sequence of SLEV was cloned into vector pSE380-MS2.Transmission electron microscopy showed that homogenous spherical particles with a diameter of about 25 nm were produced upon IPTG induction.The SLEV genomic RNA within the pseudovirus particles was resistant to DNaseⅠand RNase A digestion, and remained stable for 20 days at 37℃.These samples were validated with quantitative RT-PCR for SLEV.Conclusion The RNase-resistant and stable pseudovirus particles containing prM fragment of SLEV are constructed successfully, which can be used as positive quality control samples for RNA extraction and molecular detection.

Mechanism of Coix Seed Extract in Improving Free Fatty Acid Metabolism in Rats with Fatty Liver / 中国药师

Objective:To observe the effect of coix seed extract on non-alcoholic fatty liver disease (NAFLD), and discuss the mechanism of coix seed extract in the treatment of NAFLD in the repect of free fatty acid. Methods:Totally 60 SD rats were randomly divided into 6 groups with 10 ones in each, the normal group, the model group, the positive group ( Xuezhikang capsules, 1 g · kg-1), three coix seed extract groups respectively at high (20 g·kg-1), medium (10 g·kg-1) and low (5 g·kg-1) dosage. The normal group was given basic diet, the other 5 groups were given high fat diet to establish NAFLD rat model, the modeling time was 8 weeks, and the drug treatment started from the 5th week till the 8th week. The liver weight and fat weight and index were observed after the drug intervention. The serum total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), fatty acid synthase (FAS), acetyl coenzyme A carboxylase (ACCa-se), C two acyl coenzyme A (MALONYL-CoA) , adenosine content of protein kinase ( AMPK) and adiponectin ( ADP) activated by glycosides were detected. Results: Com-pared with those in the normal group, the lipid metabolism related indices in the model group were significantly abnormal (P<0. 05), which suggested that the model was established successfully. After the drug intervention, the lipid metabolism related indicators in the positive group and the three drug groups were adjusted in varying degrees. Compared with those in the model group, TC, FFA and AMPK expression levels increased notably in the high dosage group and the positive group (P<0. 05), and the levels of ALT, AST, FAS, ACCa-se, MALONYL-CoA decreased at the same time (P<0. 05). Coix seed extract could decrease the body weight and liver wet weight in NAFLD rats and improve the related index significantly. Conclusion: The findings indicated that coix seed extract is highly effective in improving the pharmacological effect on NAFLD induced by high-fat diet, and the mechanism is achieved through ADP-AMPK-ACCase-malony-CoA-FFA axis.

Effects of different doses of dexmedetomidine on acute brain edema in mice with traumatic brain injury / 临床麻醉学杂志

Objective To explore the effects of different doses of dexmedetomidine on acute brain edema in mice with traumatic brain injury (TBI).Methods A total of 132 male C57BL/6J mice were randomly divided into six groups:control group (group C),sham-operation group (group Sham),traumatic brain injury group (group TBI),Dex 20 μg/kg (group D20),40 μg/kg (group D40),and 60 μg/kg (group D60),n=22 in each group.The TBI animal model was established by electric controlled cortical impactor (eCCI),then intraperitoneal injected by the administration of different doses of dexmedetomidine at 0,2 and 4 h after TBI.Twenty-four hours post-TBI,brain water content was measured by the dry-wet method,histological observation was performed using HE staining,and aquaporin 4 (AQP4) and NF-κB expression were detected using Western blot assay,respectively.Then,the modified neurological scale scores (mNSS) on 1,2,3,and 7 d and Morris water maze (MWM) test on 4,5,6 and 7 d post-TBI were used to evaluate the neurologic deficit of TBI mice.Results After traumatic brain injury,the mNSS scores,the escape latency,the brain water content and the expression of AQP4 and NF-κB increased significantly in group TBI (P＜0.01).Different doses of dexmedetomidine significantly reduced the mNSS scores,the escape latency,the brain water content and the expression of AQP4 and NF-κB (P ＜ 0.05 or P ＜ 0.01).And meanwhile dexrnedetomidine can lessen neuronal degeneration,and inflammation response.Additionally,the effect was remarkably in group D60 compared with group D20 (P ＜ 0.05 or P ＜ 0.01).Conclusion Dexmedetomidine can lessen brain edema and cognition impairment induced with traumatic brain injury,which is a dose-effect relationship within 20-60 μg/kg,and this effect may be related to the downregulation of AQP4 and NF-κB expression.

Effects of Different Exercises on cAMP/CREB/ATF4 Pathway and Bone Formation in Bone of T2DM Mice / 中国运动医学杂志

Objective To observe the changes of bone formation in type 2 diabetes mellitus (T2DM) mice and the effect of different exercises on their cAMP/CREB/Atf4 pathway and bone formation.Methods Forty four-week-old C57BL/6 male mice were randomly divided into a normal control group (ZC) of 10 and a T2DM group of 30.T2DM was induced using the high-fat diet and injection of streptozotocin.Then,the T2DM mice were randomly divided into a T2DM control group (TC),a T2DM swimming group (TS) and a T2DM downhill running group (TD),each of 10.The TS and TD groups were trained for eight weeks as their group names indicated.Then the concentration of cAMP in serum was tested using the enzyme-linked immunosorbent assay (ELISA).The reverse transcription-polymerase chain reaction (RT-PCR) was used to test the mRNA expression of the cAMP-response element binding protein (CREB),activate transcription factor 4 (ATF4),osteocalcin (OC),bone gla-protein (OCN)and bone sialoprotein (BSP) in the left tibia,and Western blotting was employed to test the protein expression of CREB in the right femur.The bone marrow mesenchymal stem cells (BMSCs) were taken and induced to differentiate into osteoblasts (OBs) and dyed using the alkaline phosphatase (ALP) solution.The left side hindlimb bone was taken and scanned the bone mineral density (BMD) of the distal end using the Skyscan Micro-CT.Results Compared with group ZC,the concentration of cAMP declined in group TC.Moreover,the mRNA expression of CREB,ATF4,OC,OCN and BSP as well as the protein expression of CREB of group TC were significantly down-regulated(P＜0.01 or P＜0.05),together with the OB osteogenic capacity and BMD (P＜0.01) compared to group ZC.Compared with group TC,significant increase was observed in the mRNA expression of OC and OCN (P＜0.01 or P＜0.05),as well as the OB osteogenic capacity of group TS.The concentration of cAMP of group TD decreased,the mRNA expression of CREB,ATF4,OC and OCN,as well as the protein expression of CREB were all significantly up-regulated (P＜0.01 or P＜0.05) compared with group TD.The OB osteogenic capacity and BMD(P＜0.05) of group TD also increased significantly.Compared with group TS,the concentration of cAMP(P＜0.05) and the OB osteogenic capacity increased,and the mRNA expression of CREB,ATF4 and OC of group TD increased significantly(P＜0.01 or P＜0.05).Conclusion The bone formation metabolism of type 2 diabetic mice is inhibited.The downhill running is superior to swimming in promoting the osteoblast differentiation and bone formation,as well as the bone mineral density through activating the cAMP/CREB/Atf4 pathway in the bone of T2DM mice.