Objective:To analyze functional changes in macrophages in mouse models of vulvovaginal candidiasis (VVC) by modulating indoleamine 2,3-dioxygenase 1 (IDO1) .Methods:Forty specific-pathogen-free female ICR mice were randomly divided into 4 groups using a complete randomization method: a blank group, a VVC model group, a VVC model + 1-methyltryptophan (1-MT) group (referred to as the 1-MT group), a VVC model + interferon-γ (IFN-γ) group (referred to as the IFN-γ group), with 10 mice in each group. Except for the blank group, all the mice were injected subcutaneously with estradiol benzoate oil solution in the abdomen every other day for 6 days prior to modeling to induce pseudoestrus; after successful induction of pseudoestrus, the mice were inoculated vaginally with Candida albicans suspensions at a concentration of 2 × 10 9 CFU/ml once a day for 5 days to establish VVC mouse models, and subcutaneous injections of estradiol benzoate oil solution were continued simultaneously to maintain the pseudoestrus state; 1 day before inoculation with fungal suspensions, mice in the 1-MT group and IFN-γ group were pretreated with 1-MT and IFN-γ respectively, followed by once-daily same intervention for 6 consecutive days; mice in the blank group and VVC model group were intraperitoneally injected with physiological saline solution once a day for 6 consecutive days. On the 5th day of modeling, vaginal conditions in mice were observed and vaginal symptoms were scored; the vaginal lavage fluid was collected for smear microscopy and fungal colony counting; then, the mice were sacrificed, the vaginal tissues were collected and subjected to hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining, and the expression of IDO1 and the macrophage surface marker F4/80 was determined in the vaginal tissues by an immunofluorescence method; real-time fluorescence-based quantitative PCR (qPCR) was performed to determine mRNA expression levels of IDO1, inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1) in the vaginal tissues, and Western blot analysis to determine the IDO1 protein expression in the vaginal tissues. One-way analysis of variance was used to analyze the differences in indices among groups, and Tukey test was used for multiple comparisons. Results:Smear microscopic examination of the vaginal lavage fluid on the 5th day of modeling showed elongated hyphae with a few spores in the VVC model group, a large number of elongated hyphae aggregating in clusters with surrounding spores in the 1-MT group, and a few thin and short hyphae with a large number of spores in the IFN-γ group. Compared with the VVC model group (360.0 ± 15.9), the fungal colony counts in the vaginal lavage fluid significantly increased in the 1-MT group (523.7 ± 67.7, P = 0.002), but significantly decreased in the IFN-γ group (258.3 ± 27.57, P = 0.026). HE staining and PAS staining showed small abscess formation in the epidermis and predominant infiltration of neutrophils throughout the epidermal and dermal layers with a large number of spores and a few hyphae in the VVC model group; thickened epidermis and diffuse inflammatory infiltration predominated by neutrophils in the dermis were seen in the 1-MT group, with a large number of hyphae and spores aggregating into clusters, which were predominated by hyphae; in the IFN-γ group, spores aggregated in the epidermis without obvious hyphae, and a small amount of inflammatory cells predominated by neutrophils infiltrated the dermis. Immunofluorescence assay revealed that the relative fluorescence intensities of IDO1 and F4/80 were highest in the IFN-γ group and the 1-MT group, respectively. Western blot analysis revealed that the IDO1 protein expression in the VVC model group was significantly higher than that in the blank group ( P < 0.001) and the 1-MT group ( P < 0.05), but significantly lower than that in the IFN-γ group ( P < 0.05). qPCR showed that iNOS mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.01), and increased in the IFN-γ group compared with the blank group, VVC model group and 1-MT group (all P < 0.001); Arg-1 mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.001) and IFN-γ group ( P < 0.01), and increased in the 1-MT group compared with the blank group, VVC model group, and IFN-γ group (all P < 0.001) . Conclusion:In the VVC mouse models, upregulation of IDO1 may cause macrophage polarization toward the M1 phenotype, and inhibition of IDO1 may cause increased macrophage recruitment and exacerbate the inflammatory response.

Objective To explore the application value of rehabilitation nursing model based on early intervention in high-risk infants with cerebral palsy.Methods A total of 112 high-risk infants with cerebral palsy were selected from neonatal intensive care unit of Jiaxing Maternity and Child Health Care Hospital from January to December 2022.According to the parents'wishes,they were divided into observation group and control group,56 cases in each group.The control group was adopted routine nursing mode,and the observation group was given rehabilitation nursing mode based on early intervention on the basis of routine nursing.At correction of 1 month and 3 months,general movements quality assessment method was used to evaluate central nervous system development of two groups.Results At correction of 1 month and 3 months,the normal rate of infants in observation group was significantly higher than that in control group(P<0.05).Conclusion The rehabilitation nursing model based on early intervention can promote the neurodevelopment of high-risk infants with cerebral palsy to a certain extent,and can be popularized in early clinical nursing.

Purpose/Significance To establish an informatization platform for nursing quality control in tertiary hospitals of Qinghai province,and to analyze its influence on nursing quality.Method/Process According to the needs of nursing quality management in Qing-hai province,based on the nursing quality data platform,a nursing quality index monitoring module is established.A tertiary hospital is selected as a pilot hospital,and the nursing quality data of this hospital from January to June 2021 is selected as the control group by u-sing the historical comparative study method,and the nursing quality data collected by the informatization platform from January to June 2022 is selected as the observation group.The changes of nursing quality before and after the application of informatization platform are compared.Result/Conclusion After the application of the informatization platform for nursing quality control,the rate of physical restraint and unplanned extubation of endotracheal intubation of hospitalized patients decreases significantly,and the score of patients'satisfaction with nursing work increases significantly.The informatization platform has strong operability and clinical application value.

ObjectiveTo observe the effect of Shenling Baizhusan on the intervention of the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway by regulating ferroptosis in rats with alcoholic liver injury. MethodForty SD rats were randomly divided into model group， polyene phosphatidylcholine group， and high， medium， and low-dose Shenling Baizhusan groups， with 8 rats in each group. Another 8 SD rats were taken as blank group. The model group， polyene phosphatidylcholine group， high， medium， and low-dose Shenling Baizhusan groups were given 10 mL·kg^-1 liquor by gavage for modeling， and the blank group was given equal volume of distilled water by gavage. After 4 h of daily alcoholic administration， 143.64 mg·kg^-1 of polyene phosphatidylcholine group was given to the polyene phosphatidylcholine group， 15， 7.5， 3.75 mg·kg^-1 of Shenling Baizhusan were given to Shenling Baizhusan high， medium， and low-dose groups， respectively， and the blank group and the model group were given equal volume of distilled water. The gavage lasted for 6 weeks. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， glutamyl transpeptidase （GGT）， total cholesterol （TC）， and triglyceride （TG） were detected by automatic biochemical analyzer. The levels of tumor necrosis factor-α （TNF-α） and interleukin-β （IL-β） were detected by the enzyme-linked immunosorbent assay （ELISA）. The levels of lipopolysaccharide （LPS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， and Fe⁺ were detected by biochemical assay. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The mRNA expression levels of Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， ferritin heavy polypeptide 1 （FTH1）， and nuclear factor-κB （NF-κB） were detected by Real-time polymerase chain reaction （Real-time PCR）. The protein expression levels of Nrf2， HO-1， GPX4， FTH1， p65， and phosphorylation （p）-p65 were detected by Western blot. ResultAs compared with the blank group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the model group were significantly increased （P<0.05）. The liver showed obvious steatosis， with a large number of fat deposition， the oxidative stress and inflammatory factors were significantly increased （P<0.05）， and the level of Fe⁺ was significantly increased in model group （P<0.05）. The protein expression levels of Nrf2， HO-1， GPX4， and FTH1 was significantly down-regulated （P<0.05）， and those of p65 and p-p65 was significantly up-regulated in the model group （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly down-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly up-regulated （P<0.05）. As compared with the model group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the high-dose and medium-dose Shenling Baizhusan groups were significantly decreased （P<0.05）， liver steatosis was significantly improved， fat deposition was significantly reduced， oxidative stress and inflammatory factors were significantly decreased （P<0.05 ）， and Fe⁺ level was significantly decreased （P<0.05）. In the high-dose and medium-dose Shenling Baizhusan， the protein expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and those of p65， p-p65 were significantly down-regulated （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly down-regulated （P<0.05）. ConclusionShenling Baizhusan can effectively reduce liver injury in rats with ALD， regulate steatosis and fat deposition， and play an antioxidant and anti-inflammatory role in the liver. Its mechanism may be related to the inhibition of ferroptosis in hepatocytes by up-regulating the Nrf2 signaling pathway to improve oxidative stress

Malignant tumors of digestive system are highly prevalent malignant tumors that seriously threaten human health around the world. At present, the curative efficacy and prognosis of traditional treatment methods cannot reach the expectation, so it is urgent to find new targets for cancer treatment and realize targeted therapy for tumors. Abnormal energy metabolism in tumor cells is regarded as a hallmark of cancer, and malignant tumor cells absorb glucose through aerobic glycolysis pathway, and obtain a small amount of energy and produce lactate under the catalysis of a series of enzymes. Lactate dehydrogenase A (Lactate dehydrogenase A, LDHA), as a key enzyme in the aerobic glycolysis pathway of tumor cells, plays an important role in the metabolic changes of tumor cells. Studies have demonstrated that LDHA has high expression characteristics in a variety of tumor cells,and its high expression in clinic is often related to the poor prognosis and high metastasis rate of tumors, which is expected to be a new target for cancer therapy. This article reviews the role of LDHA in the development of digestive system tumors and the research progress of related drugs.

8-prenylnaringenin (8-PN) is a potent estrogen with high medicinal values. It also serves as an important precursor for many prenylated flavonoids. Microbial synthesis of 8-PN is mainly hindered by the low catalytic activity of prenyltransferases (PTS) and insufficient supply of precursors. In this work, a SfN8DT-1 from Sophora flavescens was used to improve the efficiency of (2S)-naringenin prenylation. The predicted structure of SfN8DT-1 showed that its main body is comprised of 9 α-helices and 8 loops, along with a long side chain formed by nearly 120 amino acids. SfN8DT-1 mutants with different side-chain truncated were tested in Saccharomyces cerevisiae. A mutant expressing the truncated enzyme at K62 site, designated as SfND8T-1-t62, produced the highest 8-PN titer. Molecular docking of SfN8DT-1-t62 with (2S)-naringenin and dimethylallyl diphosphate (DMAPP) showed that K185 was a potentially crucial residue. Alanine scanning within a range of 0.5 nm around these two substrates showed that the mutant K185A may decrease its affinity to substrates, which also indicated K185 was a potentially critical residue. Besides, the mutant K185W enhanced the affinity to ligands implied by the simulated saturation mutation, while the saturated mutation of K185 showed a great decrease in 8-PN production, indicating K185 is vital for the activity of SfN8DT-1. Subsequently, overexpressing the key genes of Mevalonate (MVA) pathway further improved the titer of 8-PN to 31.31 mg/L, which indicated that DMAPP supply is also a limiting factor for 8-PN synthesis. Finally, 44.92 mg/L of 8-PN was produced in a 5 L bioreactor after 120 h, which is the highest 8-PN titer reported to date.
Dimethylallyltranstransferase/metabolism* ; Flavonoids/metabolism* ; Molecular Docking Simulation ; Prenylation ; Saccharomyces cerevisiae/metabolism* ; Sophora/metabolism*

Clustered regularly interspaced short palindromic repeats (CRISPR) and its associated protein gene system can limit the horizontal gene transfer, thereby effectively preventing the invasion of foreign gene elements such as bacteriophages. CRISPR arrays of different bacteria are diverse. Based on the differences in the CRISPR system, this review summarizes the application of CRISPR in food-borne pathogen evolution analysis, detection and typing, virulence and antibiotic resistance in recent years. We also address bacterial detection typing method developed based on the characteristics of CRISPR arrays and the association of CRISPR with virulence and drug resistance of food-borne pathogens. The shortcomings of CRISPR in evolution, detection and typing, virulence and resistance applications are analyzed. In addition, we suggest standardizing CRISPR typing methods, improving and expanding the CRISPR database of pathogenic bacteria, and further exploring the co-evolution relationship between phages and bacteria, to provide references for further exploration of CRISPR functions.
Bacteria/genetics* ; Bacteriophages/genetics* ; CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Drug Resistance, Microbial/genetics* ; Virulence/genetics*

Objective:To investigate the changes of strains based on feature tracking in patients with hypertrophic obstructive cardiomyopathy (HOCM) after surgical myectomy and the potential factors that influenced post-myectomy global strains.Methods:A total of 27 patients with HOCM who underwent septal myectomy in Fuwai Hospital from June 2014 to July 2017 were retrospectively collected. They all received cardiac MR (CMR) cine acquisitions before and after surgery. Their preoperative and postoperative strain parameters, including radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle, septum, and lateral wall, were assessed by feature tracking. Comparisons of pre-myectomy and post-myectomy imaging parameters were performed using paired-samples t-test or Wilcoxon matched-pairs signed-ranks test. Pearson or Spearman correlation analysis and linear regression analysis were utilized to find the correlated factors of postoperative global strains. Results:Compared with preoperative strains, postoperative global LS, septal LS, lateral RS, lateral CS, and lateral LS increased statistically (all P<0.05); postoperative global RS, global CS, and septal CS decreased (all P<0.05); no statistically significant difference was observed in septal RS ( P=0.165). Age at surgery ( r=0.428, P=0.026) and preoperative myocardial maximum ventricular wall thickness ( r=-0.587, P=0.001) were both linearly related to postoperative global RS; the further multivariate stepwise linear regressions showed that only preoperative myocardial maximum ventricular wall thickness might be correlated with postoperative global RS (adjusted R 2=0.287, P=0.002). Only myocardial maximum ventricular wall thickness was linearly related to global CS ( r=0.679, P<0.001) and global LS ( r=0.588, P=0.001), respectively; univariate linear regression revealed that preoperative myocardial maximum ventricular wall thickness might be correlated postoperative global CS (adjusted R 2=0.337, P=0.001) and postoperative global LS (adjusted R 2=0.281, P=0.003), respectively. Conclusions:Cardiac surgery definitely relieves left ventricular outflow tract obstruction and generally improves longitudinal and lateral strains, but a negative impact may occur in global and septal CS and RS. Preoperative maximum ventricular wall thickness may affect postoperative global strains.

Objective:To determine the prevalence situation of adult female acne (AFA) patients and to explore the risk factors related to AFA.Methods:From September 2019 to June 2020, 290 female acne patients aged from 25 to 48 (29.57±4.50) years were surveyed with a questionnaire of risk factors and the prevalence situation of acne in the acne clinic of the Department of Dermatology, Wuxi No.2 Hospital Affiliated with Nanjing Medical University.Results:AFA occured more frequently in the jaw (95.17%), cheek (93.79%) and forehead (89.66%). Recurrent acne (38.62%) and comedonal acne (50.34%) more commonly occured. Cosmetics, endocrine, diet, genetics and other factors aggravated AFA. Age ( H=7.286, P>0.05; F=0.122, P>0.05), gonadal hormone concentrations ( Z=-0.365, P>0.05; χ 2=0.276, P>0.05), menstrual cycle ( Z=-0.274, P>0.05; χ 2=0.217, P>0.05), genetics ( Z=-1.244, P>0.05; χ 2=1.771, P>0.05) made no difference to acne grading and types. Excessive use of cosmetics could lead to increased comedo (χ 2=7.097, P<0.05). Cosmetics had no difference to acne grading ( Z=-0.065, P>0.05). Gonadal hormone concentrations were uncorrelated with menstrual cycle (χ 2=1.397, P>0.05). Conclusions:The pathogenesis of AFA is related to a variety of factors, which affect the skin barrier function and require comprehensive treatment.

OBJECTIVE： To evaluate the efficacy and safety of apremilast in the treatment of moderate-to-severe plaque psoriasis systematically. METHODS： Retrieved from PubMed， Embase， Cochrane Library， VIP， CNKI and CBM， RCTs about apremilast or apremilast combined with other drugs （trial group） versus placebo （control group） in the treatment of moderate- to-severe plaque psoriasis were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening， data extraction and quality evaluation with bias risk evaluation tool of Cochrane System Evaluator Manual 5.1.0. RESULTS： Totally 7 studies were included， involving 2 332 patients. Results of Meta-analysis showed that case number of psoriasis assessment and severity index （PASI） decreased by 75％ （PASI 75％） [OR＝6.44，95％CI（4.90，8.45），P＜0.000 01]， PASI 90％ [OR＝8.13， 95％CI（4.65， 14.22）， P＜0.000 01] and sPGA 0 or 1 [OR＝3.89，95％CI（3.00，5.05），P＜0.000 01]， the incidence of ADR [OR＝1.87，95％CI（1.44，2.43）， P＜0.000 01] in trial group were significantly more or higher than control group. Subgroup analysis by apremilast dose showed that case number of 20 mg PASI 75％ [OR＝4.72，95％CI（2.77，8.05），P＜0.000 01]， 30 mg PASI 75％ [OR＝7.05，95％CI（5.13，9.69），P＜0.000 01]， 20 mg PASI 90％ [OR＝4.27，95％CI（1.80，10.09），P＝0.001]， 30 mg PASI 90％ [OR＝11.11，95％CI（5.27，23.43），P＜0.000 01]， 20 mg sPGA 0 or 1 [OR＝2.82，95％CI（1.51，5.26），P＝0.001]， 30 mg sPGA 0 or 1 [OR＝4.13，95％CI（3.10，5.50），P＜0.000 01]， the incidence of 30 mg ADR [OR＝1.94，95％CI（1.51，2.49），P＜0.000 01] in trial group were significantly more or higher than control group. There was no statistical significance in the incidence of serious ADR [OR＝1.27，95％CI（0.77，2.07），P＝0.35] or case number of ADR leading to withdrawal [OR＝1.48，95％CI（1.00，2.20），P＝0.05] between 2 groups. CONCLUSIONS： Apremilast is effective for moderate-to-severe plaque psoriasis in dose-dependent manner and improve the quality of life， but increase the incidence of ADR.