OBJECTIVE To establish an HPLC fingerprint of Xiao’er resuqing oral liquid， and to determine the contents of twelve index components. METHODS HPLC method was adopted. The determination was performed on Venusil MP C18 column with mobile phase consisting of acetonitrile-0.1% phosphate aqueous solution （gradient elution） at a flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm， the column temperature was 30 ℃， the injection volume was 10 μL. HPLC fingerprint of Xiao’er resuqing oral liquid was established by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to evaluate the similarity. The contents of 12 components were determined， including （R， S）-goitrin， 3，5-O-dicaffeoyl quinic acid， puerarin， forsythin， forsythoside A， chlorogenic acid， baicalin， saikosaponins d， wogonoside， baicalein， emodin and chrysophanol. RESULTS The similarity of HPLC fingerprints of 13 batches of Xiao’er resuqing oral liquid was greater than 0.97， and 14 common peaks were confirmed. The contents of the above 12 index components in 13 batches of Xiao’er resuqing oral liquid were as follows： 0.078-0.172， 1.564-2.736， 1.338-2.578， 0.426-0.872， 1.477-2.628， 1.396-2.447， 4.052-9.146， 0.367- 0.692， 1.974-4.674， 1.274-2.969， 0.085-0.167 and 0.155-0.307 mg/mL. CONCLUSIONS The established HPLC fingerprint and content determination methods have high accuracy and high specificity， which can be used for the quality evaluation of Xiao’er resuqing oral liquid.

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 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.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

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 explore the effects of risk prevention in complication prevention among patients with coronary arteriography (CAG).Methods:From December 2016 to January 2018, this study selected CAG patients at Beijing Tongren Hospital as subjects by convenience sampling. All of patients were divided into control group ( n=50) and observation group ( n=50) with the method of random number table. Control group carried out routine nursing, while observation group implemented risk prevention nursing. This study compared the incidences of complications of patients between two groups. Results:The incidence of complications of patients in observation group was lower than that of control group with a statistical difference ( P<0.05). Conclusions:Risk prevention nursing can effectively reduce the implication of CAG patients which is worthy of generalization and application.

Objectives To study the clinical characteristics,diagnosis,treatment and prognosis of cancer metastases to the thyroid gland.Methods At Tianjin Medical University Cancer Hospital,from 1980 to 2016 30 patients were identified with a metastatic malignant tumor of the thyroid gland.Results Primary tumor sites were in the esophagus (26.7％),lung (16.7％),and kidney (13.3％).The median age at discovery of thyroid metastasis was 56 years old.The time lapse ranged from 0 to 108 months.There were 18 patients with metachronous metastasis with median survival of 36 months,12 patients were with synchronous metastasis,and the median survival was 8 months (P ＜ 0.01).20 patients were treated with thyroid surgery,and of which 15 patients were given post-op radiotherapy and chemotherapy.Patients who underwent thyroid resection had a median survival of 15 months,while that was 8 months in those without thyoid surgery (P ＜ 0.01).Conclusions Metastases to the thyroid gland is a rare clinical phenomenon,the prognosis of patients is mainly related to the biological behavior of primary tumors,but surgical resection and combined treatment can increase the survival rate.

As d-amino acids play important roles in the physiological metabolism of bacteria, combination of d-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate and activity of d-serine alone and in combination with -lactams against methicillin-resistant (MRSA) strains, and to explore the possible sensitization mechanisms. The activity of d-serine, -lactams alone and in combinations was evaluated both by standard MICs, time-kill curves and checkerboard assays, and by murine systemic infection model as well as neutropenic thigh infection model. An synergistic effect was demonstrated with the combination of d-serine and -lactams against MRSA standard and clinical strains. Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to -lactam alone groups. Initial mechanism study suggested possible revision of d-alanine-d-alanine residue to d-alanine-d-serine in peptidoglycan by adding of d-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, d-serine had synergistic activity in combination with -lactams against MRSA strains both and . Considering the relatively good safety of d-serine alone or in combination with -lactams, d-serine is worth following up as new anti-MRSA infection strategies.

Bacteremia is a life-threating syndrome often caused by methicillin-resistant (MRSA). Thus, there is an urgent need to develop novel approaches to successfully treat this infection. Staphylococcal accessory regulator A (SarA), a global virulence regulator, plays a critical role in pathogenesis and -lactam antibiotic resistance in . Hypericin is believed to act as an antibiotic, antidepressant, antiviral and non-specific kinase inhibitor. In the current study, we investigated the impact of hypericin on -lactam antibiotics susceptibility and mechanism(s) of its activity. We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations of -lactam antibiotics (.., oxacillin, cefazolin and nafcillin), biofilm formation and fibronectin binding in MRSA strain JE2. In addition, hypericin significantly reduced expression, and subsequently decreased and virulence-related regulators (.., ) and genes (.., and ) expression in the studied MRSA strain. Importantly, the synergistic effect of hypericin with -lactam antibiotic (.., oxacillin) translated into therapeutic outcome in a murine MRSA bacteremia model. These findings suggest that hypericin plays an important role in abrogation of -lactam resistance against MRSA through inhibition, and may allow us to repurpose the use of -lactam antibiotics, which are normally ineffective in the treatment of MRSA infections (.., oxacillin).

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.