Objective:To explore the correlation between protein energy wasting(PEW)and frailty in elderly patients on maintenance hemodialysis(MHD)and influencing factors of frailty.Methods:Clinical data of patients over 60 who had received regular hemodialysis treatment at Beijing Huairou Hospital between September to December 2021 were collected.According to Fried's evaluation criteria, patients were divided into a frailty group and a non-frailty group, and differences between the two groups were compared.Spearman correlation analysis was conducted to assess the correlation between protein energy wasting and frailty.Logistic regression was used to analyze the influencing factors of frailty in elderly patients on MHD.Results:A total of 81 MHD patients enrolled in this study, with 36 in the frailty group.The frailty group was older, had a higher proportion of patients with PEW, and underwent more months of dialysis, with a higher proportion of patients with diabetic nephropathy as the primary disease, having high levels of C-reactive protein(CRP), and having low KT/V, hemoglobin, albumin, body mass index(BMI), mid-arm circumference(MAC)and mid-arm muscle circumference(MAMC), and the differences with the control group were statistically significant(all P<0.05). The Fried frailty phenotype was positively correlated with age( r=0.021, P=0.047), but negatively associated with HGB( r=-0.329, P=0.003), albumin( r=0.021, P=0.047), BMI( r=0.021, P=0.047), TSF( r=-0.274, P=0.013), MAC( r=-0.554, P<0.001)and MAMC( r=-0.293, P=0.008). A Logistic regression equation was constructed using frailty as the dependent variable.The results showed that age, months of dialysis, KT/V, serum albumin and CRP were independent factors influencing the development of frailty in elderly patients with MHD. Conclusions:PEW and frailty coexist and interact with each other in elderly patients with MHD.Clinicians should place emphasis on the assessment of frailty and protein energy wasting in elderly dialysis patients and achieve early detection and intervention to avoid adverse clinical outcomes.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Objective:To compare the clinicopathological differences between elderly and non-elderly patients with idiopathic membranous nephropathy(IMN).Methods:Patients diagnosed with IMN via renal biopsy at Beijing Huairou Hospital, Beijing Changping Hospital of Traditional Chinese Medicine, and Beijing Hospital of Traditional Chinese Medicine from January 2017 to August 2021 were retrospectively enrolled.They were classified into the elderly group(≥65 years)and the non-elderly group(<65 years), and the clinicopathological differences between the two groups were compared.Results:A total of 207 IMN patients were included in the study, with a male to female ratio of 1.7∶1.0.There were 56 patients in the elderly group, aged(68.2±3.1)years, and 151 patients in the non-elderly group, aged(48.2±6.2)years.Compared with the non-elderly group, the elderly group had a longer time from onset to renal biopsy and a higher proportion of patients with renal insufficiency and hypertension( P<0.05). The elderly group had a lower eGFR, lower serum albumin, higher serum cholesterol, and higher low-density lipoprotein than the non-elderly group( P<0.05). The proportions of patients with glomerulosclerosis, renal tubular atrophy, and interstitial fibrosis in the elderly group were higher than in the non-elderly group( P<0.05). The positive rates of glomerular PLA2R antigen staining in the two groups were 90.6%(29/32)and 91.0%(111/122), respectively, and there was no statistically significant difference between the two groups.IgG4 deposition represented the most common IgG subtype, with 93.8%(30/32)in the elderly group and 94.3%(115/122)in the non-elderly group.There was no statistical significance between the two groups( P>0.05). Conclusions:Compared with non-elderly IMN patients, a higher proportion of elderly IMN patients has renal insufficiency, hypertension and chronic renal pathology.The glomerular deposition of pathogenic antigens in elderly IMN patients was similar to that in non-elderly IMN patients, suggesting no difference in pathogenesis between the two groups.The clinicopathological differences between the two groups may be related to age and complications.

Objective:To analyze the skin microbiota diversity in patients with pemphigus vulgaris (PV) using 16S rDNA sequencing.Methods:Ten patients with PV and 10 healthy controls were collected from the Department of Dermatology, the Third People′s Hospital of Hangzhou. Skin swabs were collected from perilesional skin (PV group) and contralateral non-lesional skin (PVn group) of the patients with PV, as well as from the corresponding body sites of the healthy controls (normal control group) . The 16S rDNA amplicon sequencing technology was used for gene sequencing and classification in all microbiota samples, and Usearch software for data cluster analysis to obtain operational taxonomic units (OTUs) and assess species abundance at the phylum, class, order, family and genus levels. Observed species index, Shannon index and Simpson index were used to estimate α diversity, and principal coordinate analysis (PCoA) was performed to analyze β diversity. Linear discriminant analysis effect size (LEfSe) analysis was conducted to identify differentially abundant species in each group. PICRUSt software was used for gene function prediction. Wilcoxon rank sum test was used as nonparametric test for comparisons between 2 groups, and Kruskal Waills test as nonparametric test for comparisons among 3 groups.Results:There were 2 002, 1 869, 1 751, 1 611 and 1 120 OTUs at phylum, class, order, family and genus levels respectively. Cluster analysis showed that skin microbiome in the 3 groups mainly consisted of Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria at the phylum level. At the genus level, Staphylococcus was the most abundant in the PV group and PVn group, and Corynebacterium was the most abundant in the normal control group. The observed species index, Shannon index and Simpson index all significantly differed among the 3 groups (all P< 0.05) , and the Shannon index and Simpson index were significantly lower in the PV group (3.24±1.30, 0.70±0.19, respectively) than in the normal control group ( P< 0.05) . PCoA analysis showed no significant difference in β diversity among the 3 groups ( P=0.054) . Rank sum test showed that the abundance of 32 species significantly differed among the 3 groups ( P< 0.05) . Among them, high relative abundance was observed in the class Bacilli enriched in the PV group, as well as the genera Micrococcus and Brevundimonas enriched in the normal control group. According to the disease duration, the patients with PV were divided into long-course PV group with disease duration of ≥ 3 months, and short-course PV group with disease duration of < 3 months. Clostridiales, Oscillibacter, Sphingomonas were enriched in the long-course PV group, and Gammaproteobacteria was enriched in the short-course PV group. Gene function prediction analysis showed that the genes related to infectious diseases were enriched in the pemphigus group. Conclusion:The 16S rDNA-based microbiota profiling suggested differences in the diversity and composition of skin microbiota between patients with PV and healthy individuals.

Studies have shown that sarcopenia can result in adverse clinical outcomes, including reduced quality of life and increased hospitalization and mortality rates.Compared with the general population, the prevalence of sarcopenia in patients with chronic kidney disease is significantly higher.This phenomenon is closely related to the complicated pathogenesis of the chronic kidney disease.In this review, we mainly discuss the epidemeology, etiology, pathogenesis and interventions of sarcopenia in patients with chronic kidney disease to provide reference for the treatment and prevention of sarcopenia in patients with chronic kidney disease.

OBJECTIVE： To observe the improvement effect and mechanism of 4-hydroxy-2-benzoxazolone （HBOA） on carbon tetrachloride-induced hepatic fibrosis in rats. METHODS： Male SD rats were randomly divided into normal control group， model group， colchicine group （positive control， 0.4 mg/kg） and HBOA low-dose， medium-dose and high-dose groups （50， 75， 100 mg/kg）， with 12 rats in each group. Except for normal control group was given constant volume of normal saline intragastrically， other groups were given 50％CCl4-olive oil solution （2 mL/kg， initial dose double） intragastrically， twice a week， for consecutive 12 weeks， to induce hepatic fibrosis model. Since the 9th week of modeling， administration groups were given relevant medicine intragastrically. Normal control group and model group were given constant volume of 0.6％ Carboxymethylcellulose sodium solution intragastrically， once a day， for consecutive 4 weeks. After last administration， the serum contents of ALT， AST， IL-1β and IL-10， the protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissue were determined. RESULTS： Compared with normal control group， the positive expression of NF-κB p65 in liver tissue was increased significantly in model group； serum contents of ALT， AST and IL-1β as well as protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissure were increased significantly， while serum content of IL-10 was decreased significantly （P＜0.05）. Compared with model group， the positive expression of NF-κB p65 in liver tissue were decreased to different extents in administration groups； serum contents of ALT， AST and IL-1β as well as protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissue were decreased significantly， while serum content of IL-10 was increased significantly （P＜0.05）. CONCLUSIONS： HBOA can improve carbon tetrachloride-induced hepatic fibrosis in rats， and the mechanism of which may be associated with relieving inflammatory reaction by blocking NF-κB signaling pathway and down-regulating the protein expression of ICAM-1.

Objective To investigate the retrobulbar hemodynamic changes in elderly patients with ischemic ophthalmopathy(IOP).Methods Three groups of 35 elderly unilateral IOP(n=35 patients),32 elderly normal eye(n=32 volunteers)and 30 non-elderly normal eye(n=30 volunteers) were recruited in our hospital for the IOP or not,for elderly(aged≥60)or not(aged ＜60).The peak systolic velocity(PSV),end-diastolic velocity(EDV),resistance index(RI),color Doppler blood stream spectrum form and arm-retinal circulation time(A-RCT) in both ophthalmic artery(OA) and central retinal artery(CRA)were measured on three groups by color Doppler flow imaging(CDFI)and fundus fluorescein angiography(FFA).Results Compared with elderly normal eye group,or with non-elderly normal eye group,the elderly unilateral IOP group showed that PSV and EDV of both OA and CRA were decreased,RI was increased,CD blood stream spectrum form was changed and A-RCT was prolonged(all P＜0.05).Compared the non-elderly normal eye group,the elderly normal eye group showed that the difference in PSV,EDV,RI,A-RCT had no statistical significance(all P ＞0.05),while CD blood stream spectrum form was changed(P＜0.05).Conclusions In the elderly unilateral IOP patients,PSV and EDV of both OA and CRA are decreased,RI is increased,blood stream spectrum form is changed,and A-RCT is prolonged.The color Doppler uhrasound-detected hemodynamic changes are displayed clearly so that CDFI can provide a reliable evidence for clinical diagnosis of IOP.

Objective To identify novel biomarkers from urinary protein profiles for the early diagnosis of nephritis in patients with Henoch-Sch(o)nlein purpura by surface enhanced laser desorption/ionization time of flight-mass spectrometry (SELDI-TOF-MS) technique.Methods Urine samples were collected from 60 untreated patients with Henoch-Schonlein purpura,including 30 patients with nephritis and 30 without.SELDI-TOF-MS technique was used to characterize the protein profile in these urine samples,and the Zhejiang University Cancer Institute-Protein Chip Data Analysis System (ZUCI-PDAS) to identify urine protein markers and construct diagnostic model for nephritis in patients with Henoch-Schonlein purpura.Results Totally,154mass peaks were identified with high quality,and two proteins at a mass-to-charge ratio (m/z) of 2454.971 and 2439.686 showed significantly differential expression between the two groups of patients (P ＜ 0.05).Seven biomarkers were used to establish a diagnostic model.As estimated by the leave-one-out cross-validation,the diagnostic model distinguished patients with nephritis from those without with a specificity of 71％ and sensitivity of 84％.Conclusions The developed diagnostic model based on SELDI-TOF-MS technique and bioinformatics is somewhat specific and sensitive for the prediction of nephritis in patients with Henoch-Schonlein purpura.

Objective: To screen and identify gene mutations of 11 Chinese patients with Hailey Hailey disease (HHD). Methods: Cases of HHD were diagnosed by history, clinical menifestations and pathology. Then genomic DNA samples of patients were extracted from perpheral blood leukocytes, and polymerase chain reaction(PCR), DNA sequencing were performed. Results: We found five mutations in ATP2C1 gene including 3 nonsense mutations and 2 splicing mutations. Four of them were novel mutations. Conclusion: Both nonsense mutation and splicing mutation could affect the rusult of transcription,translation, and the functions of protein encoded by ATP2C1 gene, so the mutations reported in this study is the underlying cause of HHD.

Objective To investigate family history, sex, age of onset, disease severity and environmental predisposing factors in vitiligo patients. Methods Eight hundred and fifteen vitiligo patients were investigated by questionnaires. Patients with family history were compared with those without such history. SPSS 10.0 software package was applied for data analysis. Results Of 815 vitiligo probands, 128 had family history and 687 did not. The heritability rate was 15.7%. Compared with general population, vitiligo probands with affected fathers or mothers had a relative risk (RR) of 132 or 72, respectively. The RRs of those with affected first-degree relatives varied from 12 to 28. There was no significant difference of mean age of onset and disease severity between patients of paternal inheritance and maternal inheritance. No significant difference was found regarding sex and mean age of onset between the groups with and without family history. However, the patients with family history were more likely to have scattered, bilateral distributed and progressive vitiligo. Of the environmental predisposing factors, the mean daily sun-exposure time was closely related to vitiligo in patients with family history. Conclusion Genetic factors may play an important role in the pathogenesis and disease severity of vitiligo.