ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

Objective To observe the effect of BOC-Phe-Leu-Phe-Leu-Phe(BOC2)on the expression of six types of mitochondrial N-formyl peptides(NFPs)in blood and two formyl peptide receptors(FPRs)in pancreatic tissue of rats with severe acute pancreatitis(SAP),and to explore its mechanism of alleviating inflammatory damage of SAP.Methods Forty male SD rats were randomly divided into four groups:the sham group,the SAP model group,the BOC2 low-dose and the BOC2 high-dose group(0.1 and 0.2 mg/kg),with 10 animals in each group.The SAP model was prepared by retrograde injection of 5%sodium taurocholate(50 mg/kg)into biliary and pancreatic ducts in the last 3 groups.BOC2 was intraperitoneally injected at 0.5 hours after SAP modeling,and samples were taken 4 hours after modeling.HE staining was used to observe pathological changes in pancreas.Western blot assay was used to detect the expression of NFPs in plasma.IHC staining was used to detect the expression of FPRs in pancreatic tissue.ELISA was used to detect interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α levels in plasma.qPCR was used to detect expression levels of inflammatory factors in local pancreatic tissue.Results Compared with the model group,the BOC2 high-dose group and the BOC2 low-dose group showed improvement in pathological phenomena,such as pancreatic bleeding,acinar cell necrosis,inflammatory cell infiltration and edema.The pancreatic injury score,pancreatic FPRs expression,plasma MT-ND1,MT-ND2,MT-ND3,MT-ND5,MT-ND6 expression,as well as expression levels of three inflammatory factors in plasma and local pancreatic tissue,were significantly reduced(P＜0.05).Conclusion BOC2 can reduce the production of inflammatory factors and alleviate SAP inflammatory damage by antagonizing mitochondrial NFPs/FPRs signaling pathway.

Objective To investigate the effects and possible mechanisms of the growth differentia-tion factor 15(GDF-15)/glial-derived neurotrophic factor receptor alpha-like(GFRAL)pathway on the progression of atherosclerosis in ApoE-/-mice.Methods Eight 8-week-old male ApoE-/-mice were randomly divided into control group and rGDF-15 group.The mice in the control group received an injection of phosphate-buffered saline via tail vein once a week after 4 weeks of high-fat diet feeding,and those in the rGDF-15 group received an injection of recombinant GDF-15(0.05 mg/kg)via tail vein once a week after 4 weeks of high-fat diet feeding.The mice were fed with high-fat diet for another 8 weeks,the body weight was monitored during this period.After 12 weeks'feeding,the mice were euthanized.Another 4 normal mice(at the same age,20 weeks old)were subjected and served as normal control group.The levels of fasting blood glucose,blood lip-ids,cortisol,and aldosterone were compared among the three groups.Oil red O staining was used to evaluate plaque size in the aorta,and immunohistochemistry was employed to assess the expression of GDF-15 and GFRAL in the brain tissue.Results The serum level of GDF-15 was higher in the rGDF-15 group than in the control group(52.59±2.90 ng/ml vs 20.09±1.27 ng/ml,P＜0.01).The weight of mice was significantly lower in the rGDF-15 group than the con-trol group during Week 11(28.60±0.22 g vs 29.47±0.25 g,P＜0.01)and 12(28.98±0.22 g vs 30.35±0.13 g,P＜0.01).The rGDF-15 group had a statistically lower level of triglycerides(0.22±0.02 mmol/L vs 0.38±0.09 mmol/L,P＜0.05),lighter plaque burden[(22.22±2.58)％vs(31.61±3.51)％,P＜0.01],and enhanced expression levels of GDF-15 and GFRAL in the brain tissue(0.088±0.007 vs 0.030±0.006,0.031±0.003 vs 0.010±0.001,P＜0.01).The levels of cor-tisol and aldosterone in the control group and rGDF-15 group were significantly higher than those in the normal group(P＜0.01).The aldosterone level in the rGDF-15 group was significantly re-duced compared to the control group(22.013.67 mg/ml vs 87.29±8.63 mg/ml,P＜0.01).Conclusion GDF-15 may regulate body weight and triglyceride and aldosterone levels through GFRAL,and then affect the progression of atherosclerosis.

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

OBJECTIVE To explore the mechanism of Xiaoyaosan in improving the abnormal glucose metabolism in chronic sleep deprivation(CSD) mice based on tyrosine hydroxylase/alpha-2a adrenergic receptor(TH/ADRA2A) signal pathway. METHODS Fifty six-week-old male C57BL/6 mice were randomly divided into two groups: 10 in the control group and 40 in the model group. The rats in the model group were deprived of sleep for 4 weeks by the method of multi-platform water environment. Fasting plasma glucose(FPG) and body mass were measured once a week for three consecutive weeks. Then, according to FPG, they were randomly divided into four groups, namely model group, guanethidine group(30 mg·kg-1·d-1) and Xiaoyaosan low and high dose groups(33.88, 101.64 g·kg-1·d-1). After grouping, continue modeling for a week. Then the drug was administered for 4 weeks. The control group and model group were treated with pure water of the same volume. Modeling continued during the administration period. On the 53rd day, blood was collected from the tail vein for the glucose tolerance test. On the 56th day, the expression of insulin(INS), noradrenaline(NE) and corticosterone(CORT) in serum was detected by ELISA. HE staining was used to observe the pathological changes of pancreatic islets. Detection of co expression of TH and INS in pancreatic tissues by immunofluorescence staining. Real-time PCR and Western blotting were used to detect the expression of ADRA2A mRNA and protein in the pancreas. RESULTS In the process of CSD modeling, compared with the initial body mass, the body mass of the model group mice decreased significantly at the end of the first week of modeling(P<0.05), and FPG increased significantly(P<0.01). After administration, compared with the control group, the glucose tolerance of the model group was significantly abnormal. The levels of NE, CORT and INS increased significantly(P<0.01), the expression level of ADRA2A mRNA and protein in the pancreas was significantly increased(P<0.01). Compared with the model group, Xiaoyaosan groups had better glucose tolerance, the levels of NE, CORT and INS decreased significantly(P<0.05), and the expression of ADRA2A mRNA and protein in the pancreas decreased significantly(P<0.05 or P<0.01). HE staining results showed that the number of cells in the islets of the model group was significantly reduced compared with the control group, and the situation was improved in all drug groups. The results of immunofluorescence staining showed that the protein content of TH in the model group increased, and the expression of TH in each group decreased after administration. CONCLUSION Xiaoyaosan can improve the abnormal glucose metabolism induced by CSD, and its mechanism may be related to the reduction of TH/ADRA2A expression.

Objective To investigate the relationship between the treatment of EGFR-TKI icotinib and the prognosis of advanced lung adenocarcinoma patients with EGFR mutation. Methods Patients with advanced lung adenocarcinoma who had EGFR19 and 21 gene mutations and were treated with EGFR-TKI icotinib were enrolled. The relationships of clinical features, EGFR gene mutation subtypes, and different sites with patients'prognosis were analyzed. Results A total of 101 patients with advanced lung adenocarcinoma were included in this study, including 58 cases (57.4%) of EGFR gene exon 19 deletion mutation (EGFR Del19) and 43 cases (42.6%) of EGFR gene exon 21 point mutation (EGFR L858R). The objective response rate was 63.4%. The mPFS and mOS were 13 months and 27 months, respectively. In addition, the mPFS and mOS of EGFR Del19 and EGFR19 mutation 746-750 were higher than those of EGFR L858R and other EGFR mutations, respectively. Meanwhile, multivariate analysis showed that the number of metastatic sites and pleural metastasis were independent influencing factors of patients'OS (P=0.027; P=0.041). The mOS of patients with the number of metastatic sites ≤3 and without pleural metastasis were 29 and 27 months, respectively. Conclusion There is no significant difference found in overall survival of advanced lung adenocarcinoma patients treated with icotinib among different EGFR mutation subtypes and sites. Herein, the overall survival time is longer in patients with less than three metastatic sites and without pleural metastasis.

OBJECTIVE: To assess the predictors and outcomes of acute kidney injury (AKI) among patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: This retrospective observational study was conducted among patients with a confirmed diagnosis of COVID-19 admitted to Hankou Hospital between January, 5 and March 8, 2020. We evaluated the association of AKI with the demographic and biochemical parameters and clinical outcomes of the patients using univariate regression analysis. OBJECTIVE: Atotal of 287 COVID-19 patients, including 55 with AKI and 232 without AKI, were included in the analysis. Compared with the patients without AKI, the patients with AKI were older, predominantly male, and were more likely to have hypoxia and pre-existing hypertension and cerebrovascular diseases. The patients with AKI also had higher levels of white blood cells, D-dimer, aspartate aminotransferase, total bilirubin, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, a higher prevalence of hyperkalemia, lower lymphocyte counts, and higher chest computed tomographic scores. The incidence of stage 1 AKI was 14.3% and that of stage 2 or 3 AKI was 4.9%. The patients with AKI had much higher mortality rate than those without AKI. OBJECTIVE AKI is an important complication of COVID-19. An older age, a male gender, multiple pre- existing comorbidities, lymphopenia, increased infection indicators, elevated D-dimer, and impaired heart and liver functions are all potential risk factors ofAKI. COVID- 19 patients with AKI that progresses into stages 2 or 3 AKI have a high mortality rate. Prevention of AKI and monitoring kidney function is critical in the care of COVID-19 patients.
Acute Kidney Injury/epidemiology* ; Aged ; COVID-19 ; China/epidemiology* ; Humans ; Male ; Retrospective Studies ; SARS-CoV-2

Objective:To investigate the clinical and pathological characteristics of acquired immunodeficiency syndrome (AIDS) patients with intestinal Talaromycosis marneffei (TM) infection. Methods:A total of 64 AIDS patients who underwent colonoscopy in Guangzhou Eighth People′s Hospital from January, 2010 to December, 2018 were retrospectively collected. Among them, 32 patients were co-infected with TM (AIDS with intestinal TM infection group) and 32 patients were not (AIDS without intestinal TM infection group) according to the colonic mucosa pathology. The clinical manifestations and pathological differences were compared between the two groups. Nonparametric rank sum test and Fisher exact probability method were used for statistical analysis.Results:The proportions of patients presented with fever, cough, retroperitoneal lymph nodes tume faction, nausea and vomiting, abdominal muscle tension, abdominal tenderness and rebound pain in AIDS with intestinal TM infection group were 28 (87.5%), 16 (50.0%), 13 (40.6%), 9 (28.1%), 8 (25.0%), 20 (62.5%) and 12 (37.5%), respectively, which were all significantly higher than those in AIDS without intestinal TM infection group 11 (34.4%), 6 (18.8%), 3 (9.4%), 2 (6.2%), 1 (3.1%), 8 (25.0%) and 1 (3.1%), respectively, the differences were statistically significant (Fisher exact test, all P<0.05). The median counts of peripheral blood CD4 + T lymphocyte, lymphocytes, monocytes, hemoglobin, platelet and albumin in AIDS with intestinal TM infection group were 13.5/μL, 0.30×10 9/L, 0.16×10 9/L, 88 g/L, 122×10 9/L and 23.5 g/L, respectively, which were all significantly lower than those in AIDS without intestinal TM infection group 207.0/ μL, 1.35×10 9/L, 0.35×10 9/L, 128 g/L, 201×10 9/L and 37.5 g/L, respectively, the differences were all statistically significant ( Z=-6.111, -6.191, -4.273, -5.353, -2.974 and-6.666, respectively, all P<0.05). Multivariate logistic regression analysis showed that CD4 + T lymphocytes <50/μL, hemoglobin <90 g/L and fecal occult blood positive were independent risk factors for AIDS with intestinal TM infection. The main manifestations of colonoscopy in AIDS with intestinal TM infection group were discontinuous ulcers (31.2%(10/32)), erosion (31.2%(10/32)) or co-exitance of ulcer and erosion (21.9%(7/32)), while suspected tumor-like eminence lesions were less common (15.6%(5/32)). The pathological features of colon mucosa were ulcer and/or erosion (53.1%(17/32)), chronic inflammation (46.9%(15/32)) and inflammatory granuloma (43.8%(14/32)). Oval or round spore with apparent septum could be seen by special staining. In AIDS with intestinal TM infection group, 27 patients were cured or improved, five patients died or deteriorated, while all patients in the AIDS without intestinal TM infection group improved after treatment without death. Conclusions:There are no specific gastrointestinal symptoms in AIDS patients with intestinal TM infection, while the patients present with decreased immunological cells and multiple colony pathological features. Specific fungal spores can be seen.

Objective To study the effect of different breast milk enhancement strategies and the incidence of complications in premature infants.Method Premature infants whose gestational age less than 34 weeks and birth weight less than 2 000 g were prospectively enrolled from January 2017 to February 2018 at the Department of Neonatology of Huangshi Maternal and Child Health-Care Hospital.According to the odd even number at the end of the hospitalization admission number,participants were assigned into 50～＜70 ml/(kg· d) group and 70～＜90 ml/(kg· d) group,When the children reached the corresponding amount of breast-feeding to be given breast milk fortifier.The demographic information,incidence of complications,rate of weight gain,percentage of extrauterine growth retardation (EUGR) and decrease of Z score at discharge were compared between groups.Result A total of 140 cases were included,with gestational age (31.4±1.9) weeks and birth weight (1 402±213) grams.Among the participants,67 infants were assigned to 50～＜70 ml/(kg·d) group,and 73 infants were assigned to 70～＜90 ml/(kg·d) group.There was no statistical difference between two groups in gender,gestational age,birth weight,length,head circumference,rates of asphyxia,ratio of intrauterine growth retardation,Z score of weight at birth,age at which breast milk fortifiers were added,full enteral feeding time,duration of parenteral nutrition,average length of hospital stay and the time of restoration of birth weight (P＞0.05).The proportion of feeding intolerance in 50～ ＜70 ml/(kg· d) group was higher than that in 70～＜90 ml/(kg· d) group (11.9％ vs.4.1％),the difference was statistical significant (P=0.013).There was no statistical difference in other complications between the two groups (P＞ 0.05).The body weight increase rate of premature infants in 50～＜70 ml/ (kg· d) group was higher than that in 70～＜90 ml/(kg· d) group,and decrease of Z score at discharge in 50～＜70 ml/(kg· d) group was lower than that of 70～＜90 ml/(kg· d),the difference was significant (P＜0.05).Conclusion Adding breast milk fortifier earlier——when the breast feeding amount of 50～＜70 ml/(kg· d)——is more beneficial to the growth and development of premature infants,it also reduces the incidence of EUGR on discharge.However,during the feeding process,it was necessary to be aware of the complications.

Objective: To construct and implement a calculation model of clinical nursing post classification. Methods: Between October to December 2018, head nurses of the hospital were screened as consultants, and Delphi method was used to determine the indicators, while the weights were assigned from the aspects of nursing workload, work quality, patient satisfaction and number of nursing night shifts. Combined with HIS data, the calculation model of clinical nursing post classification was constructed to classify clinical nursing units into different categories and levels. Results: After two rounds of expert enquiry, 82 nursing work items were identified and the objective weight assignment was determined ranging from 0.80 to16.14. According to the established calculation model and HIS data, nursing posts in clinical departments were classified into 6 levels and 3 categories, and the accurate management of clinical nursing post classification was achieved. Conclusions The construction of a calculation model is scientific and rigorous, which provides a scientific basis for dynamic nurse performance management and rational allocation of human resources. In addition, it provides a useful reference for accurate nursing management.