This work aims to evaluate a rapid detection method of carbapenem resistance genes in blood cultures based on Xpert Carba-R and preliminarily evaluate its clinical application.Methods:Sixteen strains of Enterobacterales carrying different carbapenem resistance genes were selected to prepare simulated positive blood culture samples and Xpert Carba-R was used to directly detect carbapenem resistance genes in the simulated positive blood culture. From January 2022 to June, a prospective study was conducted on a total of 117 Enterobacteriaceae-positive blood culture samples in the First Affiliated Hospital of Nanjing Medical University. Xpert Carba-R, detecting five kinds of carbapenem resistance genes in these samples, was evaluated in sensitivity and specificity compared to polymerase chain reaction sequencing. Meanwhile clinical data of positive patients was collected for prognostic analysis. Results:Of the 16 simulated specimens, 14 strains had carbapenem resistance genes detected by Xpert Carba-R, including 8 bla KPC, 5 bla NDM and 1 bla IMP, showing 100% agreement with the known results. As of the 117 clinical specimens, 28 cases were determined to be Enterobacterales harboring carbapenem resistance genes, including 24 bla KPC, 2 bla NDM and 2 bla KPC+ bla NDM. In comparison to the PCR sequencing, the sensitivity and specificity of Xpert Carba-R were both 100% for blood culture samples, and furthermore, the detection time was significantly reduced. Of the 25 positive patients, 9 cases were treated with monotherapy and 5 cases were effective, other 16 cases received combined treatment and 12 cases were effective. A total of 17 cases were effective, 8 cases were ineffective and 3 of them died, the mortality rate was 12% (3/25). Conclusion:Xpert Carba-R can rapidly and accurately detect carbapenem resistance genes in blood culture, which can provide evidence for rational drug therapy in early clinical stage.

Under the national policy background of traditional Chinese medicine（TCM）registration review and approval reform， TCM preparations in medical institutions（hereinafter referred to as medical institution preparations） have human use experience， conform to the characteristics of TCM clinical practice， and have advantages in the research and development of innovative Chinese medicines. Therefore， the research and development mode based on clinical experience prescription-medical institution preparations-innovative Chinese medicines has attracted widespread attention from the industry. However， in the process of development and use of medical institution preparations， there are generally clinical problems that restrict their transformation into innovative Chinese medicines， resulting in a relatively weak collection basis of human use experience and insufficient clinical evidence for supporting the research and development of new TCM medicines. In this paper， on the basis of sorting out the supporting regulations and relevant technical requirements of human use experience， and analyzing the clinical problems restricting the transformation of medical institution preparations， it provides suggestions for medical institutions to carry out high-quality research on human use experience of preparations in the process of TCM clinical practice from the aspects of continuously exploring clinical value， improving the construction of information system， focusing on the TCM clinical practice and giving full play to the advantages of discipline cooperation. By realizing the whole life cycle management of medical institution preparations based on three-combination evaluation evidence system， we can promote the transformation of medical institution preparations into innovative Chinese medicines.

Objective:To investigate the clinicopathological features,immunophenotype,and prognosis of head and neck spindle cell squamous cell carcinoma(SCSCC)to improve the understanding and diagnosis of this tumor.Methods:Clinicopathological data collected from January 2012 to December 2022 at the First Affiliated Hospital,Air Force Military Medical University from 20 patients with head and neck SCSCC were retrospectively reviewed for histological morphology and immunophenotype.In situ and fluorescence in situ hybridization were performed to detect EBV-encoded ribonucleic acid(EBER)status and MDM2 gene amplification,respectively.Results:The median age among the 20 SCSCC cases was 67 years with a male-to-female ratio of 4∶1.Tumor locations were laryngeal(35.0%)and sinonasal(30.0%).SCSCC presented as polypoid or exogenous growths(61.5%),often with surface ulceration(90.0%).Histologically,sarcomatoid growth pat-terns were exhibited in 75.0%of the patients(n=15),while the remainder showed granular tissue-like or angiosarcomatoid patterns.Most tumors(65.0%)displayed components of conventional squamous cell carcinomas,with a predominant occurrence of high to moderate dif-ferentiation(91.7%).In terms of immunohistochemistry,AE1/AE3 was expressed in 83.3%(15/18)of cases,while p63 and p40 expression rates were 62.5%and 66.7%,respectively.All cases were negative for EBER.The Ki-67 proliferation index ranged 10%-70%.Overall,33.3%(1/3)of the cases showed MDM2 gene amplification.Among these,the median follow-up time for 18 patients was 18.3 months(range:1-92 months),with 6 survivors and 12 deaths.Conclusions:Head and neck SCSCC is more prevalent among elderly male smokers,predominantly exhibits a polypoid growth pattern,and does not display human papillomavirus or Epstein-Barr virus infection.Diagnosis requires a compre-hensive evaluation of clinical and pathological features and immunophenotype.Surgical resection is the primary treatment method.

Objective:To observe and analyze the clinical features and prognosis of proliferative diabetic retinopathy (PDR) with chronic myeloid leukemia.Methods:A retrospective case series study. From May 2011 to December 2020, 5 patients (10 eyes) were included in this study in Eye-ENT Hospital of Fudan University. Basic information about the patient's age, gender, diabetes history and CML history were collected. The endocrine and hematological indexes of all patients were evaluated. All the patients were undertaken visual acuity, intraocular pressure, slit lamp and fundus examination and other examinations to observe the eye conditions. Ophthalmic treatments included panretinal laser photocoagulation, intravitreal injection of anti-vascular endothelial growth factor, vitrectomy. During the follow up period from 5 months to 6 years, prognosis was observed at each office visit. During the follow up period, patients' vision, intraocular pressure, anterior segment and retinal status were observed.Results:There were 4 males and a female in 5 patients. The ages were from 27 to 49 years, with the mean age of 39 years. All patients were bilateral. All patients suffered type 2 diabetes for 3 months to 13 years. Four of them were diagnosed as chronic myeloid leukemia before visiting to ophthalmologists, while the other visited to ophthalmology first due to poor vision. The initial visual acuity ranged from light perception to 0.4 and 6 eyes were less than 0.1. In addition to the typical manifestations of diabetic retinopathy, such as venous tortuous dilation, exudation, microaneurysm and neovascularization, patients also presented with Roth spot as leukemic fundus manifestations. All eyes developed to PDR stage. Abnormal thickening of the neovascular membranes may occur in the lower part of the retina, with secondary traction retinal detachment. All the eyes were treated with pan retinal photocoagulation and 9 eyes underwent pars plana vitrectomy. After treatment, retina of 8 eyes kept flat. The best corrected visual acuity ranged from no light perception to 1.0, and only 4 eyes reached more than 0.2. Unfortunately, one eye lost vision because of secondary neovascular glaucoma.Conclusions:PDR patients with CMLof fundus not only have venous tortuous dilation, exudation, microaneurysm and neovascularization, also present with Roth spot as leukemic fundus manifestations. Diabetic retinopathy combined with CML could progress rapidly, and its aggravating complications such as hyperplastic membrane, vitreous hemorrhage and traction retinal detachment may result in poor visual prognosis. Early screening and treatment can help improve the prognosis of patients.

Objective:To explore the clinical manifestations of 4 pedigrees with transthyretin related familial amyloid polyneuropathy (TTR-FAP).Methods:The clinical data were collected and analyzed from 4 pedigrees with TTR-AFP, admitted to our hospital from July 2017 to May 2019; 20 patients and 2 asymptomatic carriers of the TTR mutation gene were included. In particular, the detailed data of the 4 probands affected with TTR-FAP came from the 4 different pedigrees were collected. Results:In these 20 patients, the age of onset ranged from 30 to 65; the first symptoms of diarrhea, constipation, alternating episodes of constipation and diarrhea were found; there were damaged peripheral nerve and inexplicable weight loss; cardiomyopathy was noted in 9 patients; orthostatic hypotension was noted in 9 patients, sexual dysfunction in 5, abnormal urination in 6, and blurred vision or corestenoma in 3. TTR mutation gene was confirmed in 7 patients and pathological diagnosis was found in 3 patients. Diflunisal was used in one patient and tafamidis was used 2 patients. Twelve died and 8 patients survived among 20 patients with disease progression. All the 4 probands were male, with an average age of 49.3 years; all patients had different degrees of sensorimotor peripheral neuropathy, autonomic neuropathy and cardiomyopathy; electrophysiological examination suggested length dependent sensory motor peripheral neuropathy of the extremities, with axonal damage as the evidence; and cardiac hypertrophy was noted in echocardiography. The sural nerve biopsy of the 3 probands showed positive Congo red staining. Medical whole exon sequencing indicated that 2 probands had pathogenic mutations (TTR-E74K and TTR-A140S), and 1 proband had likely pathogenic mutation (TTR-S70R). Two asymptomatic carriers of the TTR gene mutation remained normal condition. Conclusion:The clinical manifestations of TTR-FAP include progressive sensorimotor and autonomic neuropathy, and multi-system disorders, such as combining with gastrointestinal problems, hypertrophic myocardium, inexplicable weight loss and blurred vision or corestenoma, which might be important reminders for diagnosis of TTR-FAP.

Objective　To explore the clinical manifestations,pathological characteristics and therapeutic responses of lipid storage myopathy (LSM).Methods　The clinical information of 22 LSM patients were collected and analyzed retrospectively.Results　Proximal limb muscle weakness and motor intolerance were observed in all patients.The concentrations of creatine kinase in blood were found increased to various degrees in 20 cases.EMG examinations showed myogenic damage in 18 cases.Muscle pathology examination of 22 cases showed increased lipid droplets in the muscle fibers.Follow-up data was available for 20 of all the patients after treatment.Nineteen cases were treated with low-doses prednisone,18 cases with riboflavin and 6 cases with L-Carnitine.All patients showed distinct degree of improvement of clinical symptoms within a month.After treatment for 3 months,8/22 patients were recovered except for 2 patients who were relapsed.And repeated treatment was effective.Conclusions　LSM is a curable disease.It is recommended to avoid fever,fatigue and other triggering factors.In the absence of genetic testing,riboflavin,L-carnitine,and prednisone should be used empirically.In the presence of genetic testing,targeted therapy should be performed based on gene mutations.

Objective To observe the formation of Staphylococcus aureus biofilm and the inhibitory and dispersive effects of betaine on the biofilm.Methods The inhibitory and dispersive effects of 0.1％ betaine on the biofilm from 20 strains of Staphylococcus aureus were examined by crystal violet assay.Results All the 20 strains of Staphylococcus aureus formed biofilm.The biofilm of methicillinsensitive Staphylococcus aureus (MSSA) was formed in 24 hours with peak value of absorbance (A590 nm) (1.99 ± 0.53).The biofilm of methicillin-resistant Staphylococcus atureus(MRSA) was formed in 48 hours with peak value of absorbance(A590 nm) (1.13 ±0.47).After adding betaine,the absorbance(A590 nm) of MSSA biofilm fell down to(1.74 ± 0.61) in 24 hours,while the absorbance(A590 nm) of MRSA biofilm fell down to(0.40 ± 0.12) in 48 hours,which was significantly reduced compared with the controls (t =2.43,5.84,P ＜ 0.05 respectively).When adding betaine after the biofilm formed,the absorbancies (A590 nm) of both MSSA and MRSA showed no significant difference compared with the controls (P ＞ 0.05).Conclusion Betaine could inhibit biofilm formation of Staphylococcus aureus at concentration of 0.1％,but it could not disperse the mature biofilm of Staphylococcus aureus.

Objective To investigate the effects of betaine on the formation and dispersion of biofilm of Pseudomonas aeruginosa and its drug-resistance.Methods A total of 20 strains of Pseudomonas aeruginosa were obtained from clinical inpatients.The biofilm formation abilities of the Pseudomonas aeruginosa were evaluated by violet staining,and the effects of betaine on the formation and dispersion of biofilm were studied.The minimum inhibitory concentration (MIC) values of Pseudomonas aeruginosa on ciprofloxacin were compared with the controls when biofilm was formed and inhibited.Results Biofilm was formed in all the 20 strains of Pseudomonas aeruginosa in 24 hours with absorbance (A590 nm) (1.90 ± 0.66).Betaine significantly inhibited biofilm formation of Pseudomonasaeruginosa in 24 hours compared with control group(t =4.36,P ＜ 0.01) and the maximum inhibition reached in 48 hours with absorbance(A590 nm) (1.12 ±0.60).The maximum dispersion of betaine on mature biofilm of Pseudomonas aeruginosa reached in 24 hours.The MIC range of ciprofloxacin to the 20 strains of Pseudomonas aeruginosa was 0.03 to 4 μg/mL with 0.25 μg/mL of MIC50 and 2 μg/mL of MIC90.After the biofilm was inhibited by belaine,the MIC of ciprofloxacin to Pseudomonas aeruginosa did not changed.The MIC of ciprofloxacin to biofilm-formed Pseudomonas aeruginosa was more than 16 μg/mL.Conclusion Betaine could effectively inhibit the formation of biofilm and disperse the mature biofilm of Pseudomonas aeruginosa,which may provide more choices for the treatment of clinical infection.The germicidal efficacy of ciprofloxacin has no changed on the biofilm-formed bacteria when inhibition of betaine was involved.

Objective To investigate the distribution and antimicrobial resistance profile of clinical gram-negative bacterial isolates in the First Afifliated Hospital of Nanjing Medical University during 2014.Methods Bacteria identiifcation was performed by API system or the VITEK-2 Compact automatic identiifcation system. Disk diffusion susceptibility testing or VITEK-2 Compact automatic identification system was used to determine the susceptibility to antimicrobial agents. All data were analyzed using WHONET 5.6 software.Results Among the total 7 931 clinical isolates in 2014, gram-negative bacteria accounted for 64.2% (5 088/7 931). The top three pathogens wereE. coli,A. baumannii andK. pneumoniae. Notably, during the year 2014, 195 strains of carbapenem-resistantEnterobacteriaceaewere isolated, about 6.9% of all theEnterobacteriaceae isolates. Meanwhile, 613 (66.5%) strains of multiple drug resistantA. baumannii and 197 (28.7%) strains of multiple drug resistantP. aeruginosa were isolated.Conclusion During the year 2014, the resistance of the gram-negative bacteria in this hospital is mainly characterized by carbapenem-resistantEnterobacteriaceae, multiple drug resistant A. baumanniiand multiple drug resistantP. aeruginosa. Surveillance of antimicrobial resistance is beneifcial for rational use of antibiotics.

Female ; Gallbladder Neoplasms ; complications ; Humans ; Middle Aged ; Skin Neoplasms ; secondary