Background::The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods::This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results::The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P = 0.012). Conclusions::This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Objective:To investigate the efficacy of alveolar lavage combined with montelukast in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and its effect on oxidative stress and inflammatory factors in patients.Methods:A prospective study was conducted involving 90 patients with AECOPD who were admitted to the Intensive Care Unit of Shan County Central Hospital from December 2021 to December 2022. The patients were randomly divided into a control group and an observation group, with 45 patients in each group, using the random number table method. The control group received conventional treatment, while the observation group was additionally treated with alveolar lavage combined with montelukast. Symptom score, Acute Physiology and Chronic Health Evaluation II score, overall response rate, serum levels of oxidative stress markers (malondialdehyde, 4-hydroxynonenal, and superoxide dismutase), and serum levels of inflammatory factors (C-reactive protein, tumor necrosis factor-α, interleukin-6, and procalcitonin) were compared between the two groups before and after treatment.Results:After treatment, the symptom scores for both groups decreased significantly compared with their respective scores before treatment ( t = 6.68, 11.32, both P < 0.05). After treatment, the symptom score in the observation group was significantly lower than that in the control group [(8.69 ± 0.84) points vs. (15.39 ± 1.18) points, t = 8.75, P < 0.05]. After treatment, the Acute Physiology and Chronic Health Evaluation II score in the observation group was significantly lower than that in the control group ( t = 9.19, P < 0.05). The overall response rate in the observation group was significantly higher than that in the control group [93.33% (42/45) vs. 75.56% (34/45), t = 4.56, P < 0.05]. After treatment, serum levels of 4-hydroxynonenal and malondialdehyde in the observation group were significantly lower than those in the control group ( t = 4.20, 5.15, both P < 0.05), while serum level of superoxide dismutase in the observation group was significantly higher than that in the control group ( t = 5.23, P < 0.05). After treatment, serum levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and procalcitonin in the observation group were significantly lower than those in the control group ( t = 6.86, 5.60, 8.75, 4.89, all P < 0.05). Conclusion:Alveolar lavage combined with montelukast can reduce clinical symptoms in patients with AECOPD, promote recovery, enhances clinical efficacy, decreases oxidative stress responses, increases the body's antioxidant capacity, lowers the expression of inflammatory factors, and reduces inflammatory responses.

Objective:To investigate the effects of Apelin-13 regulatory peptide on neuronal cell pyroptosis in mice modeled with cerebral ischemia-reperfusion(I/R).Methods:We prepared a mouse cerebral I/R model using middle cerebral artery embolization and Reperfusion(MCAO/R).The HT22 cell injury model was prepared by the oxygen glu-cose deprivation/reoxygenation(OGD/R),and Apelin-13 treatment was also given.Neurological function was assessed by neurological deficit score;hematoxylin-eosin(HE)staining and Nissl staining were used to observe the morphologic changes of the infarcted area of the mice;and 2,3,5triphenyltetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarcts;The expression of NOD-like receptor thermoprotein structural domain-related protein 3(NLRP3),gasdermin D(GSDMD),caspase-1,apoptosis-associated speck-like protein(ASC),interleukin 1β(IL-1β),and interleukin 18(IL-18)in brain tissues from infarcted areas or HT22 cells was detected by Western Blot,and IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA)in serum of mice and culture supema-tants;The cell viability and cell damage of HT22 were detected by CCK-8 kit and lactate dehydrogenase(LDH)assay kit,respectively;caspase-1 activity was measured by caspase-1 activity kit in HT22 cells;and the expression of caspase-1 and GSDMD was observed by immunofluorescence staining in HT22 cells.Results:Apelin-13 significantly improved neurological function and cerebral infarct volume in I/R mice,and attenuated pathological damage in the in-farcted area.It also reduced the serum levels of IL-1β and IL-18.In addition,Apelin-13 reduced the expression of mol-ecules such as NLRP3,GSDMD,caspase-1,IL-1β,and IL-18 in the cerebral infarct area of mice.In vitro experiments showed that Apelin-13 significantly increased the viability of OGD/R-treated HT22 cells,decreased caspase-1 activity,and reduced the LDH content,as well as decreased the expression of molecules such as NLRP3,GSDMD,caspase-1,IL-1β,IL-18,and so on,in OGD/R-treated HT22 cells.Conclusion:Apelin-13 inhibits pyroptosis through the NL-RP3/caspase-1/GSDMD pathway in cerebral ischemia/reperfusion mice and thus exerts neuroprotective effects.

Objective:To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF).Methods:A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE ( n=1 127) and SE ( n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results:In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio ( OR)=2.75, 95% confidence interval ( CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L ( OR=2.07, 95% CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L ( OR=1.91, 95% CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% ( OR=2.45, 95% CI 1.63-3.69, P<0.01), left atrial diameter>40 mm ( OR=1.54, 95% CI 1.16-2.07, P=0.003), and CHA 2DS 2-VASc score≥3 ( OR=15.14, 95% CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE ( OR=0.28, 95% CI 0.15-0.51, P<0.01). Conclusions:History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA 2DS 2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.

【Objective】 To evaluate the efficacy and safety of different doses and frequencies of oral Sildenafil in the treatment of erectile dysfunction (ED). 【Methods】 The randomized,open clinical trial included 120 ED patients who met the inclusion and exclusion criteria. The patients were randomly divided into the following groups:on-schedule (25 mg/day),on-demand (50 mg,taken irregularly half an hour before each sexual life),new regular group (25 mg/day,50 mg more before each sexual life),regular group (100 mg/time,twice/week). All treatments lasted for 8 weeks. The follow-up indexes included the five-item International Index of Erectile Function (IIEF-5),Erection Hardness Scale (EHS) and Sexual Encounter Profile (SEP2/3). The adverse reactions were recorded. 【Results】 The IIEF-5 scores of the four groups were significantly higher than those after baseline treatment (P<0.001),but there was no significant difference among the four groups (P>0.05). In terms of effective rate,at the 16th week,there were significant differences between the on-demand group (10.7%) and new regular group (62.1%),and between the on-demand group (10.7%) and regular group (50.0%) (P<0.001). In terms of EHS, the percentage of grade 4 patients in regular group was significant higher than that in the on-demand group at the 8th week and 16th week (all P<0.05). In terms of positive rate of SEP-3,there was a significant difference between the on-demand group and regular group (P=0.042) at the 16th week. In the course of treatment,there were transient adverse reactions such as headache,blurred vision,stuffy nose and back pain,which did not affect the treatment. 【Conclusion】 All of the four treatment methods of oral sildenafil showed good efficacy. Both regular group and new regular group maintained good clinical efficacy during the follow-up,which is better than that of the on-demand group. The new regular scheme can be used as a new,safe and effective treatment option.

Objective:To detect the expression levels of laboratory of genetics and physiology 2 (LGP2), retinoic acid inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) in children with hand, foot and mouth disease (HFMD), and to explore their possible clinical significance in HFMD.Methods:Fifty children with HFMD, who visited Second Affiliated Hospital of Xi′an Jiao Tong University, Xi ′an Children′s Hospital and Xi ′an Central Hospital from May 2020 to May 2021, were selected as the research subjects, and 20 children with physical examination at the same age during the same period were selected as the control group.Children with HFMD were divided into enterovirus 71 (EV-A71) type and coxsackievirus A6 (CV-A6) type according to the results of pathogen detection, and then divided into mild group and severe group according to the severity of the disease.The relative mRNA expression levels of LGP2, RIG-I and MDA5 in each group, and the correlation among the three proteins were compared and analyzed.Results:Among 50 cases of HFMD, 26 cases were EV-A71 type (16 cases were mild and 10 cases were severe) and 24 cases were CV-A6 type (17 cases were mild and 7 cases were severe). There was no significant difference in age and sex between HFMD group and control group ( P>0.05). The relative expression levels of LGP2 mRNA in EV-A71 and CV-A6 HFMD cases were 2.37(1.78, 3.25)% and 1.88 (1.35, 3.13)%, lower than that in control group [2.97(2.61, 3.55)%]. Only the difference between CV-A6 HFMD children and control group was statistically significant ( Z=-2.310, P=0.021). The relative expression levels of RIG-I mRNA in EV-A71 and CV-A6 HFMD cases were 9.95 (7.79, 14.62)% and 9.78(7.04, 15.83)%, lower than that in control group [18.47(13.00, 21.07)%]. The differences were all statistically significant ( P<0.05). The relative expression levels of MDA5 mRNA in EV-A71 and CV-A6 HFMD cases were 4.41(2.82, 5.99)% and 3.98 (2.18, 7.41)%, lower than that in control group [5.10(3.52, 7.71)%], but the differences were not statistically significant.There were no significant differences in the relative expression levels of the three indicators between the mild and severe groups of children with EV-A71 or CV-A6 HFMD.The expression levels of LGP2, RIG-I and MDA5 mRNA were highly correlated( P<0.001). Conclusion:The relative expression levels of LGP2, RIG-I and MDA5 mRNA in children with HFMD are decreased in different degrees than those in normal children.And there is a correlation among them.

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
China ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Humans ; Mutation ; Poly T ; RNA, Messenger/genetics*

Objective To explore the radiation shielding optimization plan for a medical proton cyclotron developing and commissioning building at various commissioning stages. Methods According to the maximum source termsat different commissioning stages, we used the empirical formula to estimate the instantaneous dose rate at the point of interest outside the shield of the building, and optimized the building’s shielding ateach commissioning stage. Results When adding 1.0 m mobile concrete shielding blocks (“blocks” below) each to wall 3 and wall 4 at the cyclotron commissioning stage, 1.0 m blocks to wall 4 and 1.25 m blocks to wall 5 at the beam transport line commissioning stage, and 1.0 m blocks to wall 9 and 0.4 m blocks to the ceiling at the simulated treatment room commissioning stage, the dose rates at the points of interest outside the shield could meet the dose rate limit requirements. Conclusion The application of mobile concrete shielding blocks not only meets the shielding requirements, but also has economical and space-saving advantages, conforming to the principle of shielding optimization. This can be an approach to the optimization of radiation shielding for high-energy particle accelerators or similar scientific projects.

Objective:To screen the serum exosomal microRNAs differentially expressed in early pancreatic cancer patients and evaluate the diagnostic value of exosomal hsa-let-7f-5p.Methods:From January 2019 to January 2020, 19 patients with early pancreatic cancer (early pancreatic cancer group) and 16 patients with chronic mass-forming pancreatitis (pancreatitis group) were selected from Affiliated Hospital of Nanjing University of Chinese Medicine who underwent surgery and were confirmed by pathology. Serum samples of the two groups of patients were collected. At the same time, serum samples of 19 healthy volunteers were selected as the normal control group. The exoEasy Maxi Kit was used to isolate serum exosomes. The structural characteristics of exosomes were observed by transmission electron microscopy (TEM). The particle size of exosomes was observd by nanoparticle tracking analysis. CD 63 and CD 81, the specific protein marker on the surface of exosomes, were identified by western blotting. The total RNA of exosomes was extracted by the miRNeasy Serum/Plasma Kit, and a small RNA library was constructed after quality inspection. With reference to the small RNA database, the differentially expressed exosomal microRNAs in early pancreatic cancer group, pancreatitis group and normal control group were filtered out. The miRNA candidates were validated by quantitative polymerase chain reaction (qPCR) and different expressions of them were analyzed. The role of target genes and metabolic pathways of candidate miRNAs in the occurrence and development of early pancreatic cancer were analyzed by gene ontology (GO) and Kyoto Encyclopeda of Genes and Genomes(KEGG) enrichment pathway. Results:The isolated serum exosomes can be seen to have cup-like vesicle with the double lipid layer by TEM. The main peak of the particle size of target exosomes was about 150 nm. The expression of exosome specific protein markers CD 63 and CD 81 was positive. Comparing the expression of miRNAs among early pancreatic cancer group, pancreatitis group and normal control group, the specific tumor marker exosomal hsa-let-7f-5p was screened out in this study, and its expression in early pancreatic cancer group was significantly higher than that in pancreatitis group and normal control group (both P values <0.05). Receiver operating characteristic curve analysis (ROC) showed that the area under curve (AUC) of exosomal hsa-let-7f-5p to distinguish pancreatic cancer from pancreatitis was 0.843 (95% CI 0.640-1.000). The sensitivity and specificity were 100% and 81.82% respectively. The AUC for distinguishing pancreatic cancer from normal controls was 1.000 (95% CI 1.000-1.000), and both sensitivity and specificity were 100%. The diagnostic efficiency of exosomal hsa-let-7f-5p was equivalent to that of CA19-9 ( P>0.05). The GO analysis results showed that target genes of exosomal hsa-let-7f-5p were mainly involved in complement activation lectin pathway in biological processes, and the proteins expressed by target genes were mainly distributed in cilium, and molecules mostly functioned by combining with nitric-oxide synthase. The KEGG pathway enrichment analysis showed that the target genes were closely related to MAPK signaling pathway. Conclusions:Serum exosomal hsa-let-7f-5p has the potential to be a diagnostic biomarker for early pancreatic cancer.

Objective:To investigate the damage and mechanism of artemisia annua pollen on tight junction of human nasal mucosa epithelial cells (HNEpC).Methods:HNEpC were cultured in vitro. Different concentrations of artemisia annua pollen (0, 20, 40, 80, 100, 160, 200 μg/ml) were used to intervene the cells for 24 h, and the cell proliferation activity was detected by the CCK-8 method. The expression and phosphorylation of p38MAPK signaling pathway were detected by Western Blot before and after the intervention of SB203580, a p38MAPK inhibitor in HNEpC. Immunofluorescence chemical staining, Western Blot and quantitative real-time PCR (qPCR) were used to observe the expression and distribution of tight junctions Occludin and Claudin-1. SPSS 21.1 software was used for statistical analysis.Results:CCK-8 results showed that, compared with the control group, the proliferation activity of HNEpC increased after 6 h intervention with different concentrations of artemisia annua pollen (all P<0.05). After 12 h of intervention, the proliferation activity of HNEpC in the 20, 40, 80, 100 and 160 μg/ml groups was not significantly changed (all P>0.05), while that in the 200 μg/ml group was decreased ( P<0.05). After the intervention for 24 h, the proliferation activity of cells in the 20 and 40 μg/ml groups was not significantly changed (all P>0.05), while that in the 80, 100, 160 and 200 μg/ml groups was decreased (all P<0.05). Immunofluorescence staining showed that the Occludin and Claudin-1 proteins in the normal control group were localized on the cell membrane and expressed more and formed a ring structure around the cell membrane. However, under the intervention of high concentration artemisia annua pollen, its expression level decreased, appeared broken, fuzzy, and nonuniform distribution. Western Blot and qPCR results showed that after 24 h of intervention, the expression levels of HNEpC Claudin-1 protein and its mRNA in the pollen groups (40, 80, 100, 160, 200 μg/ml) of artemisia annua decreased compared with those of those of the control group (mRNA expression levels were 0.567±0.214, 0.443±0.109, 0.462±0.160, 0.497±0.134, 0.388±0.076 compared with 1.001±0.067, respectively, all P<0.05). However, the mRNA of Occludin protein and its mRNA only decreased in the 200 μg/ml treatment group (mRNA expression level was 0.631±0.109 compared with 1.016±0.026, P<0.05), while all the other treatment groups increased (mRNA expression levels were 1.258±0.134, 1.827±0.103, 2.429±0.077, 1.707±0.085, 1.477±0.066 compared with 1.016±0.026, respectively, all P<0.05). Western Blot showed that p-p38MAPK expression increased after intervention with 100, 160, 200 μg/ml artemisia annua pollen for 24 h. SB203580 could inhibit the decreasing expression of Occludin caused by artemisinin pollen (mRNA expression was 1.255±0.179 compared with 0.631±0.109, P<0.05), but had no effect on Claudin-1 protein expression. Conclusion:Pollen from artemisia annua may activate p38MAPK signaling pathway and destroy the close connection of HNEpC.