The retina has a complex and delicate function and structure, containing a large number of neuronal cells with extremely limited regenerative capacity, which are susceptible to damage and apoptosis under pathological conditions such as ischemia and hypoxia, resulting in irreversible vision loss. Retinal diseases are very common, such as retinitis pigmentosa(RP), age-related macular degeneration(ARMD), diabetic retinopathy(DR), and glaucoma. Most of the diseases in this category are treated symptomatically, which is effective but has some limitations in neuroprotection. Vascular endothelial growth factor(VEGF)-B is functionally relatively inert in the VEGF family, and unlike pro-angiogenic VEGF-A, VEGF-B shows functional inertia in angiogenesis but exhibits significant neuroprotective effects. VEGF-B is a potent anti-apoptotic, antioxidant factor that can regulate the expression of apoptotic genes and enhance the expression of glutamic acid decarboxylase 1 by binding to VEGFR-1 to activate the ERK1/2 or Akt pathway, in addition to decreasing the expression of glutamate, resulting in retinal neuroprotective effects. In this article, the protective effects of VEGF-B on retinal neuronal cells were reviewed to provide new ideas for the treatment of retina-associated diseases.

Background Environmental noise pollution is serious, and there are few studies on the effects of long-term noise exposure during sleep on cognitive function and possible biological clock mechanism. Objective To explore the cognitive impairment induced by noise exposure during sleep in mice and possible biological clock mechanism, and to provide a theoretical basis for the protection against noise exposure. Methods Twenty male C57BL/6J mice were randomly divided into a control group and a noise-exposed group, 10 mice in each group. The noise-exposed group was exposed to sleep-period noise using a noise generator for 12 h (08:00–20:00) per day for a total of 30 d. The calibrated noise intensity was set at 90 dB. No intervention was imposed on the control group. At the end of the noise exposure, cognitive function of mice was examined using the new object recognition experiment and the open field test, and the hippocampal tissue damage of mice were evaluated by Nissl staining, ionized calcium binding adaptor molecule 1 (Iba1) immunofluorescence staining, and real-time fluorescence quantitative PCR for inflammatory factors and biological clock genes. Oxidative stress indicators in the hippocampus of mice were also detected by assay kit. Results After noise exposure during sleep period, the results of new object recognition experiment showed that the discrimination index of mice in the noise-exposed group was 0.06±0.04, which was significantly lower than that of the control group (0.65±0.13) (P<0.05). The results of open field test showed that the central activity distance of the noise-exposed group was (242.20±176.10) mm, which was significantly lower than that of the control group, (1548.00±790.30) mm (P < 0.05), and the central activity time of the noise-exposed group was (0.87±0.64) s, which was significantly lower than that of the control group, (6.00±2.86) s (P < 0.05). The Nissl staining results showed that compared with the control group, neurons in the hippocampus of the noise-exposed mice were shrunken, deeply stained, disorganized, and loosely connected. The immunofluorescence results showed that microglia in the hippocampus of the noise-exposed mice were activated and the expression of Iba1 was significantly increased compared with those of the control group (P<0.05). The real-time PCR results of showed that the mRNA levels of the biological clock genes Clock, Per2, and Rev-erbα were significantly increased compared with those of the control group (P<0.05), and the mRNA level of Per1 was significantly decreased compared with that of the control group (P<0.05); and the mRNA levels of IL-18, IL-6, iNOS, and NLRP3 in the hippocampal tissues of mice were significantly increased compared with those of the control group (P<0.05). The results of oxidative stress evaluation showed that compared with the control group, reduced glutathione content was significantly reduced in the noise-exposed group (P<0.001). Conclusion Noise exposure during sleep period can lead to the destabilization of biological clock genes in hippocampal tissues and trigger hippocampal neuroinflammation, which can lead to the activation of microglia and cause cognitive impairment in mice.

Objective To study the initial pumping speed of sodium citrate in single plasma exchange with regional citrate anticoagulation(RAC).Methods From January to December 2021,15 patients and 67 times of treatment with local sodium citrate anticoagulation single plasma exchange in the hospital were in-cluded in the study.According to the initial pumping speed of sodium citrate,they were included in the low-speed group(n=33)and the high-speed group(n=34).The transmembrane pressure,filter pressure drop and venous pressure were compared between the two groups at 30 minutes,one hour and two hours after treatment.The free calcium concentration after plasma separator at 15 minutes and one hour after treatment,and the coagulation of plasma separator and extracorporeal circulation pipeline at the end of treatment were compared between the two groups.The concentration of free calcium,blood gas analysis and electrolyte were compared at the beginning of treatment,one hour after treatment and at the end of treatment.Results The free calcium concentration after the filter was monitored at 15 minutes and one hour of treatment in both groups was within the effective range of anticoagulation recommended by the guidelines.There were no lips,fingertip numbness and hand-foot convulsions in the two groups during the treatment,and no bleeding oc-curred after the treatment.There were four cases of hypocalcemia and two cases of alkalosis in the low-speed group,and 13 cases of hypocalcemia and eight cases of alkalosis in the high-speed group.The difference be-tween the two groups was statistically significant(P＜0.05).There were 15 cases of grade Ⅰ coagulation and five cases of grade Ⅱ coagulation in plasma separator and pipeline in the low-speed group,while there were 14 cases of grade Ⅰ coagulation and four cases of grade Ⅱ coagulation in plasma separator and pipeline in the high-speed group.There was no significant difference between the two groups(P＞0.05).Conclusion In plasma exchange treatment,according to the low initial pumping speed,RAC can not only ensure the anticoagulant effect,but also reduce the incidence of complications such as hypocalcemia and alkalosis.

Objective To investigate the peripheral retinal defocus and its influencing factors in children and adoles-cents with low to moderate myopia.Methods Totally 281 children and adolescents aged 6-15 years were included in the study,and only the right eye was selected.After cycloplegic refraction as well as axial length(AL)and average corneal curvature(AveK)measurements,the patients were divided into low myopia(LM)group(-3.00 D≤SE≤-0.50 D)and moderate myopia(MM)group(-6.00 D≤SE＜-3.00D)according to spherical equivalent(SE),and stratified compari-sons were made according to AL[AL1 group(23.00 mm≤AL≤24.00 mm),AL2 group(24.00 mm＜AL≤25.00 mm),and AL3 group(25.00 mm＜AL≤26.00 mm)]and AveK[AveK1 group(40.00 D≤ Ave K≤43.00 D)and AveK2 group(43.00 D＜AveK≤46.00 D)].Multispectral refraction tomography was used to measure the refraction difference value(RDV),in-cluding TRDV(0° to 53°),RDV-15(0° to 15°),RDV-30(0° to 30°),RDV-45(0° to 45°),RDV-15-30(15° to 30°),RDV-30-45(30° to 45°),RDV-45-53(45° to 53°),RDV-S(superior),RDV-I(inferior),RDV-T(temporal)and RDV-N(na-sal).The RDV was compared in the groups divided according to SE,AL and AveK individually,and the correlation be-tween RDV and age,SE,AL and AveK was analyzed.Moreover,the factors affecting RDV in all ranges were analyzed by multiple linear regression.Results Compared with the LM group,the MM group had significant increases in TRDV,RDV-30,RDV-45,RDV-15-30,RDV-30-45,RDV-45-53,RDV-S,RDV-I and RDV-N(all P＜0.05)and no significant differ-ence in RDV-15 and RDV-T(both P＞0.05).According to the comparisons of AL groups and AveK groups,the TRDV,RDV-30,RDV-45,RDV-15-30,RDV-30-45,RDV-45-53,RDV-S,RDV-I and RDV-N in the AL2 group were significantly higher than those in the AL1 group(all P＜0.05);the TRDV,RDV-30,RDV-45,RDV-15-30,RDV-30-45,RDV-45-53,RDV-S and RDV-N in the AL3 group were significantly higher than those in AL2 and AL1 groups,and RDV-I and RDV-T in the AL3 group were significantly higher than those in the AL1 group(both P＜0.05);the TRDV,RDV-30,RDV-45,RDV-15-30,RDV-30-45,RDV-45-53,RDV-S,and RDV-I in the Ave K1 group were significantly higher than those in the AveK2 group(all P＜0.05).The correlation analysis showed that TRDV,RDV-45,RDV-30-45,RDV-45-53,RDV-S and RDV-N were positively correlated with age and AL and negatively correlated with SE and Ave K;RDV-30,RDV-15-30 and RDV-I were positively cor-related with AL and negatively correlated with SE and AveK;RDV-T was positively correlated only with AL;RDV-15 was not correlated with age,SE,AL and AveK.Multiple linear regression analysis showed that age was the influencing factor of RDV-45-53 and RDV-S;AL was the influencing factor of TRDV,RDV-30,RDV-45,RDV-15-30,RDV-30-45,RDV-45-53,RDV-S and RDV-T;AveK was the influential factor of RDV-I;SE had no significant effect on RDV in all ranges.Conclu-sion Peripheral retinal defocus in children and adolescents with low to moderate myopia has reached hyperopic defocus,and hyperopic defocus is the least in patients with relatively short AL.Age,AL and AveK can affect peripheral retinal defo-cus in children and adolescents with low to moderate myopia,among which AL is the most important influencing factor.

Objective:To investigate the effects of early applying of basic fibroblast growth factor (bFGF) on corneal haze formation after surface ablation surgery in rabbits.Methods:The right eyes of 60 healthy New Zealand white rabbits received photorefractive keratectomy (PRK) and were randomized into PRK+ normal saline group, PRK+ bFGF group and simple PRK group, with 20 rabbits in each group.Normal saline solution and bFGF were topically administered according to grouping, respectively, 3 times per day, 1 drop for each time until the sacrifice of the animals, and no drug was used in the PRK group.Another 8 normal rabbits were served as blank control group.The corneal healing response and haze formation were evaluated by anterior segment photography and anterior segment optical coherence tomography (AS-OCT) and graded based on Fantes criteria.Corneal histopathology was examined by hematoxylin-eosin staining.Immunohistochemistry was used to detect the expression of transforming growth factor-β 1(TGF-β 1), α-smooth muscle actin (α-SMA) and matrix metalloproteinase-2 (MMP-2) in cornea.This study protocol was approved by the Experimental Animal Ethic Committee of Affiliated Hospital of Binzhou Medical University (20180209-03). The use and care of the animals complied with the Statement of ARVO. Results:The corneal epithelium was completely healed in 3-4 days following surgery and there was not significantly different in healing time among the three groups.( F=0.57, P=0.57). The haze grading was significantly different among different groups at different time points ( Fgroup=41.736, P<0.01; Ftime=129.445, P<0.01) and showed the highest score in the PRK+ bFGF group on the 28th day after operation.On the 7th day after surgery, AS-OCT image showed that the surface reflection of corneal epithelium was continuous and smooth and corneal epithelium was not tightly attached to the superficial stromal layer; the reflection of the superficial stromal layer was enhanced in all the operation groups.The proliferation of corneal epithelial cells and superficial stromal layer in the operation area were seen under the optical microscope, and the arrangement of collagen fibers in the stromal layer was disordered with the most obvious changes in the PRK+ bFGF group in comparison with the PRK+ normal saline group and the simple PRK group, and these findings became worse on postoperative 28 days.The corneal epithelial surface reflection in the blank control group was continuous and smooth.Immunohistochemistry showed that a few MMP-2 positive cells were seen in the blank control group.TGF-β 1, α-SMA and MMP-2 proteins were positively expressed in the corneas 7 days after surgery in the three groups, and their expressions were the most obvious in the PRK+ bFGF in comparison with the PRK+ normal saline group and the PRK group and were enhanced 28 days after operation, showing statistically differences (all at P<0.05). Conclusions:Early application of bFGF following surface ablation surgery promotes the proliferation of corneal epithelial cells and irregular arrangement of collagen in the superficial stromal layer, which is associated with the expressions of haze-related factors TGF-β 1, α-SMA and MMP-2 in corneas.

BACKGROUND: Chronic noise exposure is one environmental hazard that is associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. However, the comprehensive understanding of the link between chronic noise stress and AD is limited. Herein, we investigated the effects of chronic noise exposure on AD-like changes in senescence-accelerated mouse prone 8 (SAMP8). METHODS: A total of 30 male SAMP8 mice were randomly divided into the noise-exposed group, the control group, and aging group (positive controls), and mice in the exposure group were exposed to 98 dB SPL white noise for 30 consecutive days. Transcriptome analysis and AD-like neuropathology of hippocampus were examined by RNA sequencing and immunoblotting. Enzyme-linked immunosorbent assay and real-time PCR were used to further determine the differential gene expression and explore the underlying mechanisms of chronic noise exposure in relation to AD at the genome level. RESULTS: Chronic noise exposure led to amyloid beta accumulation and increased the hyperphosphorylation of tau at the Ser202 and Ser404 sites in young SAMP8 mice; similar observations were noted in aging SAMP8 mice. We identified 21 protein-coding transcripts that were differentially expressed: 6 were downregulated and 15 were upregulated after chronic noise exposure; 8 genes were related to AD. qPCR results indicated that the expression of Arc, Egr1, Egr2, Fos, Nauk1, and Per2 were significantly high in the noise exposure group. These outcomes mirrored the results of the RNA sequencing data. CONCLUSIONS These findings further revealed that chronic noise exposure exacerbated aging-like impairment in the hippocampus of the SAMP8 mice and that the protein-coding transcripts discovered in the study may be key candidate regulators involved in environment-gene interactions.

Objective: To study the effects of different holding gun methods and gun weight on health when standing guard, and propose a way to support the health of long-term standing guard soldiers. Methods: We created different percentile mannequins by Classic JACK, and adjusted the standing guard posture based on its standards for soldiers. The pressure on lumbar L4/L5 and moment on ankles and knees were analysied for different holding gun methods and gun weight. Then the mathematical models of joint load, gun weight and body mass index were studied by multiple regression analysis. Results: Holding gun methods and gun weight influence the force characteristics on ankles, knees and lumbar L4/L5. Holding gun with a brace and hands applying downward force -2 kgf could significantly reduce lumbar L4/L5 pressure. When the hand force is -5, -3, -4, -3, -2, -1, 0, 1, 2 kgf, and the weight of the gun is 0, Lumbar vertebrae L4/L5 joint pressure of people with different body mass index(P₁, P₅, P₅₅, P₉₅, P₉₉) are the smallest, respectively 269, 281, 321, 408, 444 N, and the same change trend occurs when the weight of the gun is 2, 4, and 8 kg.The moment on ankles and knees were less with the same holding gun method and the hands downward force ranged from 0 to -4 kgf, and the higher the body mass index is, the more the hands downward force needed to make the moment on ankles and knees zero. That is, the moment on ankles could be zero when the hands downward force ranged from -1 to -3 kgf, the moment on knees could be zero when the hands downward force ranged from -1.1 to -3.7 kgf. Conclusion To reduce the pressure on lumbar L4/L5 and moment on ankles and knees, so as to cut down occupational risk of long-standing operation, we advise the long-term standing guard soldiers holding gun with a brace and hands applying downward force -2 kgf.

Objective To investigate the effect of conbercept on rabbit's haze after photorefractive keratectomy (PRK).Methods Sixty-four pedigree New Zealand white rabbits were randomly divided into PRK group,normal saline solution group,conbercept 0.5 mg group,conbercept 1.0 mg group,with 16 rabbits in each group.PRK was performed on right eyes,PRK group only received PRK,the other three surgery groups were given postoperative subconjunctival injection of 0.05 ml normal saline solution,0.5 mg (0.0:5 ml) conbercept and 1.0 mg(0.10 ml) conbercept,respectively.In addition,another 8 rabbits were randomly chosen as normal control group.The healing of postoperative corneal epithelial was observed by slit lamp biomicroscope,and the degrees of haze were graded based on Fantes.Eight rabbits in the surgery groups and 4 rabbits in the normal control group were killed in the first week and the fourth week.The corneal tissue was stained by hematoxylin-eosin,and the expressions of transforming growth factor-β1 (TGF-β1),α-smooth muscle actin (α-SMA) and matrix metalloproteinase-2 (MMP-2)were detected by immunochemistry.The use and feeding of experimental animals followed the Relevant Regulations of the Animal Management Committee of Binzhou Medical University.This study protocol was approved by Ethic Committee of the Affiliated Hospital of Binzhou Medical University (No.201701-08).Results Corneal epithelium of all operative rabbits healed completely at 3-5 days and no significant difference in healing time between the groups after operation (F=0.37,P =0.77).The degree of haze in each surgery group reached the highest value at about 4 weeks after operation,and haze in the conbercept 1.0 mg group was the most serious,followed by PRK group and normal saline solution group,haze in conbercept 0.5 mg group was significantly alleviated (Fgroup =20.114,P =0.000;Ftime =8.084,P =0.006).Hematoxylin-eosin staining showed that corneal epithelial cells and fibroblasts in superficial stroma proliferated in one week after PRK,which lead to the disorder of cells and collagen fibers,and the extent of hyperplasia was the same as that of haze.Immunohistochemistry showed that at one week after operation,the expressions of factors in PRK group and normal saline solution group were apparently lower than that of conbercept 1.0 mg group,but were apparently higher than that of conbercept 0.5 mg group,and the expressions of the factors were the weakest in normal control group,with significant differences between them (all at P ＜ 0.05).Conclusions Subconjunctival injection of appropriate conbercept can inhibit the formation of haze and the proliferation of corneal epithelium and superficial stroma,but overdose of conbercept leads to opposite effects.

Yeast autolysis under solid-state fermentation can effectively promote the release of various active substances, thereby improving the quality of yeast products. The optimal process for yeast autolysis under solid-state fermentation was obtained by optimizing the autolysis temperature, autolysis time and the zinc ion concentration. We analyzed the indexes of free amino acid, soluble protein and α-amino nitrogen in the fermentation material, as well as A₂₆₀/A₂₈₀ ratio to determine yeast autolysis process conditions in the solid-state fermentation. On the basis of the obtained data, L₉ (3³) orthogonal test was designed to optimize the solid-state fermentation parameters for yeast autolysis: temperature at 40, 50 and 55 °C; time 12, 18 and 24 h; zinc ion concentration 2, 4 and 8 mg/kg. The optimum process conditions for yeast autolysis were: autolysis temperature 55 °C, time 18 h, zinc ion concentration 2 mg/kg, and soluble protein content reached 9.31 mg/g, free amino acid 14.36 mg/g, α-amino nitrogen 10.16 μg/g and A₂₆₀/A₂₈₀ 1.73. After optimization of the process, the soluble protein, free amino acid and α-amino nitrogen contents of the yeast autolysis production can be significantly increased, thereby obviously improving the quality of the composite culture.
Amino Acids ; Autolysis ; Fermentation ; Humans ; Hydrogen-Ion Concentration ; Nitrogen ; Saccharomyces cerevisiae ; Temperature

Objective To investigate influential factors and incidence of postpartum urinary retention after forceps delivery. Method The clinical data of 216 cases of puerperas undergoing forceps delivery in our hospital from January 2012 and July 2015 were collected and investigated in terms of postpartum urinary retention as well as its influencing factors. Results The incidence rate of postpartum urinary retention was 24.07%(52/216).Logistic multivariate regression analysis showed the significant positive variables for the outcomes included:the first stage of labor and postpartum 2h bleeding.Conclusion The first stage of labor time and postpartum 2h bleeding are the high risk factors of uroschesis after forceps delivery.