Objective:To investigate the effect of rare ginsenosides (RGS) on reproductive injury induced by cyclophosphamide (CP) in female rats.Methods:Twenty-four female rats were divided into four groups [normal control (NC), RGS, CP, and CP+RGS group] with 6 rats in each group. CP group (the model group) and CP+RGS group (the treatment group) were intraperitoneally injected with CP 30 mg/kg for 5 days for modeling, and CP+RGS group was given RGS intragastric intervention. General growth status of rats in each group was observed, the organ index was calculated, and the pathological changes of ovary, uterus, liver and kidney were observed by hematoxylin-eosin staining. Serum levels of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), pro-inflammatory factors interleukin (IL) 6, IL-1β, tumor necrosis factor-α were detected. The urine samples were collected after RGS treatment for metabonomics analysis. Metabolomic profiling based on ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS) was used to analyze and determine the urine metabolites of rats in each group.Results:Compared with NC group, the ovary index of CP group [(0.054±0.015) %] was significantly decreased ( P<0.05), the uterus index [(0.293±0.036) %] and estradiol level [(62.9±6.4) pmol/L] were significantly decreased (all P<0.01), serum levels of FSH, LH, IL-6 and IL-1β [(20.4±1.0) U/L, (29.0±3.0) U/L, (185.4±28.6) ng/L, (72.9±2.0) ng/L, respectively] were significantly increased (all P<0.01). Compared with CP group, the ovary index in CP+RGS group [(0.075±0.010) %] was significantly increased ( P<0.05), serum estradiol level [(122.1±16.2) pmol/L] was significantly increased ( P<0.01), serum FSH, IL-1β and IL-6 levels [(16.7±1.0) U/L, (111.8±17.4) ng/L, (60.1±2.2) ng/L, respectively] were significantly decreased (all P<0.01). Metabonomics analysis results showed that, a total of 352 metabolites were detected in urine, of which 12 were found to be potential markers associated with reproductive injury according to the screening standard. After treatment with RGS, differential metabolites were improved in the direction of NC group. Pathway enrichment suggests that the therapeutic effect of RGS was related to multiple metabolic pathways, including purine metabolism and taurine and hypotaurine metabolism. Conclusion:RGS might reduce inflammation and thus ameliorate the damage caused by CP to the reproductive system of female rats by affecting purine metabolism and other pathways.

Central serous chorioretinopathy (CSC) is a common macular disease, which can lead to the loss of central vision in young patients. Although the disease is self-limited to some extent, there is no shortage of patients with prolonged course and recurrent attacks, eventually leading to irreversible visual impairment. Therefore, taking reasonable treatment in a certain period is particularly important for the visual prognosis of patients. Although thermal laser photocoagulation of leakage points and photodynamic therapy (PDT) have achieved good effects, there are risks of retinal damage and retinal pigment epithelium atrophy. Subthreshold micropulse laser (SMLP) is a kind of subthreshold short pulse laser, which does not cause visible damage to the retina and is safer. In the era of lack of PDT drugs, SMLP has gradually become an important means of clinical treatment for CSC, especially for patients with no obvious leakage point or subfoveal leakage point. An in-depth understanding of the mechanism of action of SMLP and its efficacy and safety in the treatment of CSC is helpful for the promotion and application of SMLP in the clinical treatment of CSC.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective:To understand the effect of a new tracheal tube fixation device in the "double fixation" of oral tracheal intubation for critically ill patients in adult emergency department.Methods:A retrospective analysis of patients with oral tracheal intubation admitted to our EICU from January 2016 to June 2017 was performed using traditional tape and inch band fixation as a control group; the experience of treatment from July 2017 to December 2018 for patients with oral tracheal intubation, the new double-fixation method of tracheal tube fixation device was used as the observation group. The degree of displacement, oral cleanliness, facial skin allergies and injuries, and comfort of the two groups of patients was compared.Results:The rate of tracheal displacement in the experimental group was mildly 11.2% (11/98), moderately 5.1% (5/98), and the control group was mildly 24.2% (15/62), moderately 14.5% (9/62) and severe 6.5% (4/62). The incidence of facial skin allergy and skin damage was 6.1% (6/98), 0, and the control group was 24.2% (15/62), 11.3% (7/62), the difference was statistically significant ( Z value was -4.021, χ2 value was 24.48, P<0.05). The comfort score of the test group was (1.05±1.01) points, which was significantly higher than (2.10±1.71) points of the control group ( t value was 4.920, P<0.01). Conclusions:The new type of tracheal tube fixation device "dual fixation" for critically ill patients with mechanical ventilation through oral endotracheal intubation is visually beautiful, and has good firmness and comfort. It can effectively reduce the occurrence of adverse events and has good application value.

Objective: To investigate the application of low molecular weight heparin modified injection in the nursing of patients with acute myocardial infarction. Methods: A total of 90 patients with myocardial infarction who underwent subcutaneous injection of low molecular weight heparin from May 2017 to May 2018 were enrolled in the study. The patients were divided into the control group and the observation group according to the different injection and treatment methods. The control group used the traditional injection method of low molecular weight heparin, and the observation group used the low molecular weight heparin modified injection method. Forty-five patients were observed and compared for the degree of subcutaneous hemorrhage, incidence of induration and pain. Results: The incidence of subcutaneous induration and subcutaneous hemorrhage in the observation group were 10.16% (64/630) and 19.84% (125/630), respectively. The control group was 16.19% (102/630) and 31.11% (196/630), respectively. The difference between the groups was statistically significant (χ²=10.019, 21.073, both P<0.05). The pain score of the observation group was 1.29±0.21, and the control group was 1.86±0.28. The difference between the two groups was statistically significant (t=40.877, P<0.05); the subcutaneous mild, moderate, and severe bleeding in the observation group were 17.30% (109/630), 2.54% (16/630), and 0, respectively, and the control group was 21.90% (138/). 630), 8.41% (53/630), 0.79% (5/630), the difference between the two groups was statistically significant (χ²=4.235, 20.990, 4.019, all P < 0.05). Conclusions Low molecular weight heparin modified injection method for myocardial infarction patients can effectively reduce the incidence of subcutaneous hemorrhage and induration, reduce the degree of subcutaneous hemorrhage and pain, suitable for clinical promotion.

Salidroside, as one of the main active ingredients of Rhodiala plant, has the effects of anti-hypoxia, anti-radiation, anti-fatigue, anti-tumor, hypoglycemia and improving immunity. With the increasing demand for salidroside and the decreasing of plant resources, microbial production of salidroside has attracted much attention due to its advantages of short period and easy controlling. At present, microbial production of salidroside is still at the basic research stage. In order to make it easier for researchers to understand the advances of microbial synthesis of salidroside, the biosynthesis pathways, uridine diphosphate glucosyltransferases, wild strain/natural enzymes and engineered strain/recombinant enzymes were reviewed.
Biosynthetic Pathways ; Glucosides ; metabolism ; Phenols ; metabolism

Background Cornea astigmatism can be effectively corrected by implanting Toric intraocular lens (IOL) during cataract surgery and therefore improve visual acuity of patients.However,the decentration and rotation position errors were inevitable sometime.What's the difference of effect of position errors on quality of image between spherical IOL and Toric IOL needs further research.Objective This study was to evaluate the optical performance and wavefront with rotation and decentration of Toric IOL.Methods Different decentration for SN60AT IOL(spherical IOL) and Toric IOL in Hwey-Lan Lion model eyes was set with the role as follows:decentration 0.25 mm to 0.75 mm in a 5°-interval from 0° to 90°.Furthermore,Toric IOL was rotated at 5° and 10°,respectively.Then the image performances of SN60AT IOL and Toric IOL at different decentration distances and rotated degrees were evaluated with modulation transfer function (MTF) and value of wavefront aberration under all conditions.Results At the centration,the MTF curves of spherical IOL and Toric IOL were similar under 3,4 and 5 mm pupil diameter at each spatial frequency.Under the condition of 4 mm pupil diameter,when the decentration was 0.25 mm,the MTF values of SN60AT IOL at 6 c/d and 12 c/d were 0.581 087 and 0.411 960,respectively.T3 IOL were 0.454 259 and 0.382 313,T4 IOL were 0.426 020 and 0.360 490,T5 IOL were 0.425 606 and 0.359 877.When the decentration was 0.50 mm,the MTF values of SN60AT at 6 c/d and 12 c/d were 0.573 073 and 0.412 787,respectively.T3 IOL were 0.450943 and 0.379481,T4 IOL were 0.423 153 and 0.356 664,T5 IOL were 0.422 881 and 0.356 230.When the decentration was 0.75 mm,the MTF values of SN60AT at 6 c/d and 12 c/d were 0.560 038 and 0.413 624,respectively.T3 IOL were 0.445 597 and 0.374 322,T4 IOL were 0.418 522 and 0.350 087,T5 IOL were 0.418 468 and 0.349 976.When the IOL decentralized along 0°,5°,10°,90°meridian line,the MTF values were almostly same.The root mean square (RMS) of spherical IOL and Toric IOL was increased when the IOL decentralized from 0 mm to 0.75 mm,with the most increasing level in coma aberration and slight increase in trefoil aberration.When the T4 IOL decentralized from centre to 0.75 mm,the coma increased from 0 to C(3,-1)-0.049 79 μm,C (3,1)-0.037 59 μm and the trefoil aberration increased from 0 to C (3,3) 0.005 72 μm,C (3,-3) 0.004 64 μm.With the increase of rotation degrees (from 5°to 10°) of Toric IOL,the MTF was worse at high spatial frequency.Toric IOL rotation caused the increase of astigmatism and residual astigmatism and spherical error,but not high order aberration.Conclusions The tolerance of Toric IOL to decentration is very close to the spherical IOL,and optical performance is only associated with the amount of decentration but not direction.The aberration caused by Toric IOL decentration is mainly coma.The rotation of Toric IOL causes astigmatism error but not high order aberrations.

Objective To study the functions of peroxisome proliferator-activated receptorγ(PPARγ), retinoic acid X receptor α (RXRα) and cyclooxygenase 2 (COX-2) in the carcinogenesis of cervical squamous cell carcinoma (SCC). Methods The expressions of PPARγ, RXRα and COX-2 in 17 cases of normal cervical epithelium (NCE), 72 cases of squamous intraepithelial lesion (SIL) and 42 cases of cervical SCC were detected with immunohistochemical method respectively. Results The positive expression rates of PPARγ in the NCE, SIL and cervical SCC group were 23.5 % (4/17), 58.3 % (42/72) and 83.3 % (35/42) respectively; the positive expression rates of RXRα in the NCE, SIL and cervical SCC group were 29.4 %(5/17), 54.2 % (39/72) and 90.5 % (38/42) respectively. No significant expression of COX-2 was found in the NCE, while the positive expression rates of COX-2 in SIL and cervical SCC were 36.1 % (26/72) and 57.1 %(24/42) respectively. The positive expression rates of PPARγ, RXRαand COX-2 in high-grade SIL group were higher than those in low-grade SIL group (all P<0.05). In cervical SCC group, the positive expression rate of COX-2 with lymph node metastasis was higher than that without lymph node metastasis (χ2= 3.98, P= 0.04). Conclusion PPARγ, RXRαand COX-2 might be all involved in the carcinogenesis of SCC.

The chalcone synthase (CHS) superfamily of the type III polyketide synthases (PKSs) generates backbones of a variety of plant secondary metabolites. Benzalacetone synthase (BAS) catalyzes a condensation reaction of decarboxylation between the substrates of 4-coumaric coenzyme A and malonyl coenzyme A to generate benzylidene acetone, whose derivatives are series of compounds with various biological activities. A BAS gene Pcpks2 and a bifunctional CHS/BAS PcPKSI were isolated from medicinal plant P. cuspidatum. Crystallographic and structure-based mutagenesis studies indicate that the functional diversity of the CHS-superfamily enzymes is principally derived from small modifications of the active site architecture. In order to obtain an understanding of the biosynthesis of polyketides in P. cuspidatum, which has been poorly described, as well as of its activation mechanism, PcPKS2 was overexpressed in Escherichia coli as a C-terminally poly-His-tagged fusion protein, purified to homogeneity and crystallized, which is helpful for the clarification of the catalytic mechanism of the enzyme and lays the foundation for its genetic engineering manipulation.
Butanones ; Catalytic Domain ; Crystallization ; Fallopia japonica ; enzymology ; Polyketide Synthases ; genetics ; metabolism

Glycosyltransferases (GTs) catalyze the transfer of a sugar residue of an activated sugar donor to an acceptor molecule. Many families 1 GTs utilize an uridine diphosphate (UDP) activated sugar as donor in the glycosylation reaction, and most of these belong to a group of GTs referred to as the UGTs. The relationship between the degree of amino acid sequence identity and substrate specificity of the plant UGTs is highly complicated, and the prediction of substrate specificity based on phylogenetic analyses need to be improved by more biochemical characterization. This review summarizes the three dimensional structures of plant UGTs published in the Protein Data Bank (PDB), including the detailed substrate interactions with the sugar and receptor binding pockets and mutational analyses of some critical amino acids. It will be helpful for biochemical characterization the substrate specificity of the individual UGT, and lay the foundation for the enzymatic and genetic manipulation of plant UGTs in the future.
Amino Acid Sequence ; Glycosylation ; Glycosyltransferases ; chemistry ; Phylogeny ; Plant Proteins ; chemistry ; Plants ; enzymology ; Protein Structure, Tertiary ; Substrate Specificity ; Uridine Diphosphate ; chemistry