Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe3O4@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe3O4@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe3O4@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T2 magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

Clinical analysis of antineutrophil cytoplasmic antibody-associated vasculitis in 13 children / 中华肾脏病杂志

Objective:To investigate the clinical manifestations, pathological characteristics, treatment and prognosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in 13 children.Methods:The clinical and pathological data of 13 cases of AAV in children′s Hospital of Nanjing Medical University from June 2000 to December 2021 were retrospectively analyzed.Results:Among the 13 cases, 12 cases were diagnosed with microscopic polyangiitis (MPA) and 1 case was granulomatosis with polyangiitis (GPA), including 10 females and 3 males. The onset age ranged from 3 years and 11 months to 13 years and 10 months. The most frequently involved organ was the kidney (12 cases, 92.3%), followed by respiratory system (7 cases, 53.8%), skin (5 cases, 38.5%), digestive system (4 cases, 30.8%), nervous system (4 cases, 30.8%) and cardiovascular system (3 cases, 23.1%). There were 10 cases with orthotic anemia, 7 cases with positive antinuclear antibody, and 3 cases with mildly decreased complement C3. Among the 12 children with renal impairment, 9 cases were accompanied by abnormal renal function at the beginning of the disease. Renal biopsy was classified according to the Berden as follows: sclerotic in 5 cases, crescentic 3 cases, focal in 2 cases and mixed in 2 cases. All children were treated with glucocorticoid combined with immunosuppressant. During the follow-up time from 8 months to 128 months, 4 cases acquired complete remission, 8 cases achieved partial remission and 1 case recurred after complete remission, and 7 cases progressed to chronic kidney disease stage 5. Three children with complete remission underwent repeated renal biopsy, including 2 cases of mixed type and 1 case of crescent type initially, and all changed to focal type.Conclusions:AAV in children occurs mainly in school-age female, and most of AAV in children is MPA. The clinical manifestations are various. Most of them have renal damage and anemia, and lung damage is also common. Patients with skin purpura onset may be misdiagnosed as Henoch-Schonlein purpura, and AAV with ANA positive or complement reduction should exclude systemic lupus erythematosus. Once the renal function is abnormal in AAV, especially estimated glomerular filtration rate<60 ml·min -1·(1.73 m 2) -1 and the pathological classification is sclerotic type or crescent type, it is difficult to reverse even after active treatment. Early diagnosis and treatment are very important for AAV.

Progress of diagnosis and treatment of Fabry disease / 中华实用儿科临床杂志

Fabry disease is a rare X-linked hereditary lysosomal storage disease, which is caused by GLA gene mutation, reduced or absent activity of α-galactosidase A (α-Gal A), which disturbs the glycosphingolipid metabolism and leads to accumulation of metabolic substrates globotriaosylceramide (GL-3) and its derivative deacetylated GL-3 (Lyso-GL-3), which results in multiple organ diseases.Because the clinical manifestations lack specificity, it is necessary to combine the detection of enzyme activity, biomarker GL-3 and Lyso-GL-3, pathology and gene detection for early diagnosis.At present, the main treatment methods are enzyme replacement therapy and oral chaperone therapy.The purpose of this paper is to update the diagnosis and treatment of Fabry disease.

Role of exosomes in the development, progression, diagnosis, and treatment of liver fibrosis / 临床肝胆病杂志

An increasing number of studies have demonstrated that exosomes are closely associated with liver fibrosis and mediate the process of liver fibrosis by participating in cytokine secretion, macrophage activation, extracellular matrix remodeling, and hepatic stellate cell activation. This article summarizes that the resolution of liver fibrosis requires the reduction of pro-inflammatory and fibrotic cytokines, the reduction of extracellular matrix protein production, the increase of collagenase activity, and finally the loss of activated myofibroblasts. It is believed that exosomes play an important role in the treatment of liver fibrosis and are potential markers for diagnosis and treatment, and in future studies, it is necessary to improve exosome extraction techniques and standardization of treatment quantification.

Clinical features and genetic variants of Dent disease in 10 children / 中华儿科杂志

Objective@#To summarize the clinical features and genetic analysis results of 10 children with Dent disease.@*Methods@#The clinical data and gene test results of 10 boys aged from 8 months to 12 years with Dent disease diagnosed in Children's Hospital of Nanjing Medical University from January 2014 to July 2017 were analyzed retrospectively.@*Results@#All patients had insidious onset, 5 cases were found to have proteinuria on routine urine examination after hospitalization duo to other diseases, 4 cases were admitted to hospital because increased foams in the urine, and 1 case was found to have proteinuria on health checkup. All cases presented with low molecular weight proteinuria, urine protein electrophoresis showed that the proportion of low molecular weight protein was greater than 50%, 7 cases had nephrotic-range proteinuria, but none had hypoproteinemia. Six cases had hypercalciuria, 3 cases had nephrocalcinosis, 1 case had nephrolithiasis, 2 cases had glomerular microscopic hematuria, in 1 case urine glucose wa weakly positive but blood glucose was normal. All patients had normal renal function, normal serum calcium, no hypophosphoremia and none had rickets. Genetic analysis results showed that 7 patients with variants in the CLCN5 gene, including 2 nonsense variants (p.R637X, p.Y143X), 3 missense variants (p.A540D, p.G135E, p.G703V), 1 deletion variant (exons 9, 10, 11, 12, 13, 1 missing), and 1 frameshift variant (p.T260Tfs*10). Three cases had missense variants of OCRL gene (p.I274T, p.I371T, p.F399S). Except for p.R637X and p.I274T, the other 8 cases had newly discovered variants. Five patients underwent a renal biopsy, the biopsy revealed focal global glomerulosclerosis in 3 patients, mild mesangial proliferative glomerulonephritis in 1 patient and renal minimal change in 1 patient. Mild focal tubular atrophy and interstitial fibrosis were noted in three cases. Mild segmental foot process effacement was noted under electron microscope in all five cases.@*Conclusions@#All the children with Dent disease had insidious onset, low molecular weight proteinuria is the main clinical manifestation, most cases presented with nephrotic-range proteinuria, but there was no hypoalbuminemia, some cases were not associated with hypercalciuria. The pathogenic genes in most cases were CLCN5 and a few were OCRL. The types of genetic variation include missense variant, nonsense variant, deletion variant and frameshift variant. Although Dent disease is a renal tubular disease, renal biopsy suggests that most cases are associated with glomerular lesions.

Analysis of clinical diagnosis and treatment of 20 children with hypophosphatemic tickets / 中华实用儿科临床杂志

Objective To analyze the clinical diagnosis and treatment data of 20 children with hypophosphatemic rickets (HR) in order to improve the clinical diagnosis and treatment of HR.Methods The retrospective analysis of clinical data of 20 cases with HR who were hospitalized at Children's Hospital of Nanjing Medical University from May,2010 to April,2016 was performed to summarize the clinical characteristics.All patients were analyzed for the phosphate regulating gene with homologies to endopeptidase on the X chromosome(PHEX) gene by direct sequencing.If no mutations were detected,multiplex ligation-dependent probe amplification analysis was performed.Results All of the 20 cases with HR showed different degrees of growth retardation and typical X-ray rickets.After treatment,the clinical features were improved.Height standard deviation score (HSDS) was improved significantly with longer treatment time,and the difference was statistically significant(P =0.027).There was a correlation between the blood phosphorus fluctuation and secondary hyperparathyroidism(P ＜ 0.05).Nineteen cases had PHEX gene mutations.Truncating mutations was the most frequent mutation type,and 4 new mutations were found.Conclusions Clinical characteristics,laboratory test results and X-ray examination are important clinical index for the diagnosis of HR,and PHEX gene test can be used as an important auxiliary diagnostic tool.Early diagnosis and treatment can significantly improve the clinical manifestations of the patients.

Clinical Observation of Berberine in Intervening Insulin Resistance of Polycystic Ovary Syndrome / 广州中医药大学学报

Objective To evaluate the clinical efficacy of berberine for the treatment of insulin resistance (IR) in women with polycystic ovary syndrome (PCOS).Methods Sixty PCOS-IR women were randomized into treatment group and control group,30 cases in each group.At the end of the trial,26 cases in the treatment group (4 cases dropped out) and 29 cases in the control group (one case dropped out) completed the trial.The treatment group was treated with berberine orally,and the control group was treated with metformin orally,the treatment for the two groups lasting 3 months.Before and after treatment,we observed the parameters of body mass index (BMI),homeostasis model of assessment for insulin resistance index (HOMA-IR),fasting plasma glucose (FPG),fasting insulin (FINS),2-hour postprandial glucose after oral glucose tolerance test (OGTT2hPG) and 2-hour postprandial insulin after OGTT (OGTT2hINS),blood lipid levels of total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C),and sexual hormones of follicle-stimulating hormone (FSH),luteotropic hormone (LH),testosterone (T) and LH/FSH ratio.Results BMI,HOMA-IR,TC,TG and LDL-C of the two groups were decreased after treatment (P ＜ 0.05 or P ＜ 0.01 compared with those before treatment),but the differences between the two groups were insignificant(P ＞ 0.05).Serum levels of T and LH as well as LH/FSH ratio in the treatment group were also decreased (P ＜ 0.05 or P ＜ 0.01 compared with those before treatment and those in the control group after treatment).Conclusion Berberine can improve HOMA-IR,decrease serum sexual hormones levels,and regulate the blood metabolism in PCOS-IR women,and its effect is similar to that of metformin.

Effects of Xuebijing Injection on serum CRP, TNF-α and IL-6 levels in patients with severe acute organophosphorus pesticide poisoning / 中成药

AIM To explore the effects of Xuebijing Injection (Carthami Flos,Salviae miltiorrhizae Radix et Rhizoma,Paeoniae Radix Rubra,etc.) on serum CRP,TNF-α and IL-6 levels in patients with severe acute organophosphorus pesticide poisoning (AOPP).METHODS Seventy-two cases of patients with AOPP treated from Jan 2014 to Mar 2016 in the emergency department of our hospital were randomly divided into two groups,the control group treated with atropine,pralidoxime chloride and conventional treatment,and the observation group combined with Xuebijing Injection.The dynamic changes of serum CRP,TNF-α and IL-6 levels,and clinical curative effects were compared between the two groups.RESULTS The serum CRP,TNF-α and IL-6 levels in the two groups were decreased in turn before the treatment,at the 3rd,7th days after the treatment,and the serum CRP,TNF-α and IL-6 levels in the observation group were significantly lower than those in the control group;the dosage of atropine,time of cholinesterase activity recovered 60％ and hospital stay in the observation group were significantly less than those in the control group;the rebound rate of the observation group was lower than that of the control group.The acute respiratory distress syndrome (ARDS) rate in the observation group was significantly lower than that in the control group.All the differences had statistical significances (P ＜ 0.05).CONCLUSION Xuebijing Injection can effectively inhibit the inflammatory response,reduce the incidence of complications,shorten the course,and improve the clinical efficacy in the treatment of patients with AOPP.

Epidemic condition and molecular subtyping of ciprofloxacin and cefotaxime co-resistant Salmonella Indiana isolated from retail chicken carcasses in six provinces, China / 中华预防医学杂志

<p><b>OBJECTIVE</b>To elucidate the epidemic condition and molecular subtyping of ciprofloxacin and cefotaxime co-resistant Salmonella Indiana (S. Indiana) isolated from retail chicken carcasses in six provinces of China.</p><p><b>METHODS</b>A total of 2 647 Salmonella strains isolated from retail chicken carcasses collected from six provinces of China were subjected to antimicrobial susceptibility testing. All Salmonella isolates co-resistant to ciprofloxacin and cefotaxime were further characterized by serotyping, extended-spectrum beta-lactamases (ESBLs) producing strains screening and pulsed field gel electrophoresis (PFGE) typing.</p><p><b>RESULTS</b>Among 2 629 Salmonella isolates tested, 227 (8.52%) isolates were co-resistant to ciprofloxacin and ceftazidime/cefotaxime (Beijing: 11.67% (99/874), Jilin: 8.20% (60/726), Guangdong: 1.39% (7/502), Jiangsu: 15.61% (42/260), Shaanxi: 8.56% (16/186), Inner Mongolia: 0 (0/81)), and 224 of them were identified as S. Indiana. 213 (95.10%) isolates of S. Indiana were ESBLs producing strains. All ciprofloxacin and cefotaxime co-resistant S. Indiana isolates developed a multi-drug resistant profile and 17.86% (40/224) of them were resistant to all antibiotics tested except carbapenems, and 50.89% (114/224) of them resistant to 9 antibiotics, additionally, 25.45% (57/224) of them showed multi-drug resistance to 8 antibiotics. All ciprofloxacin and cefotaxime co-resistant S. Indiana isolates were divided into 32 PFGE clusters and 150 PFGE patterns. Strains of S. Indiana from same or different sampling site and time seemed to either share the same PFGE patterns or be differential to each other in different regions.</p><p><b>CONCLUSION</b>The results indicated that chicken carcasses collected from parts of China were heavily contaminated by ciprofloxacin and cefotaxime co-resistant S. Indiana and could serve as an important reservoir of ciprofloxacin and cefotaxime co-resistant Salmonella. Molecular subtyping results indicated that cross contamination or common pollution source might be in these strains.</p>

Clinical Observation of Mass-dissipating Acupuncture Therapy in Relieving Gynecologic Chronic Pelvic Pain / 广州中医药大学学报

Objective To observe the clinical effect of mass-dissipating acupuncture therapy for relieving gynecologic chronic pelvic pain. Methods Sixty gynecologic chronic pelvic pain patients were equally randomized divided into treatment group and control group. Both groups were treated with enema and oral use of Chinese medicine, and the treatment group received mass-dissipating acupuncture therapy additionally. Seven days constituted one period of treatment, and the treatment lasted 2 periods. After treatment, the patients were followed up for one month. The visual analog scale ( VAS) was used for the scoring of pain before and after treatment and during the follow-up. The quality of life ( QOL) was evaluated with 36-item short-form health survey (SF-36) before treatment and during the follow-up. Results (1) At the end of the treatment, the VAS scores of the two groups were decreased significantly, the difference being significant compared with those before treatment ( P<0.01) . The difference of pre- and post-treatment VAS scores between the two groups had statistic significance ( P<0.01) . The results of follow-up showed that pain VAS scores were still decreased in both groups as compared those at the end of treatment, the difference being significant (P<0.01). (2) The results of follow-up showed that the scores of each dimension of SF-36 were obviously increased in both groups as compared those before treatment (P<0.01), and the increase was obvious in the treatment group (P<0.05 or P<0.01). Conclusion Mass-dissipating acupuncture therapy combined with enema and oral use of Chinese medicine is effective in relieving gynecologic chronic pelvic pain, enhancing therapeutic effect and improving QOL.

Morphologic and texture features in classifying the malignant and benign breast nodules in ultrasonography / 重庆医学

Objective To develop a computer-aided diagnosis(CAD)system with automatic contouring and morphologic and tex-tural analysis to aid on the classification of breast nodules on ultrasound images .Methods A modified Level Set method was pro-posed to automatically segment the breast nodules(46 malignant and 60 benign nodules) .Following ,16 morphologic features and 17 texture features from the extracted contour were calculated and principal component analysis(PCA)was applied to find the optimal feature vector dimensions .Fuzzy C-means classifier was utilized to identify the breast nodule as benign or malignant with selected principal vectors .Results The performance of morphologic features was 78 .30% for accuracy ,67 .39% for sensitivity and 86 .67%for specificity ,while the latter was 72 .64% ,58 .70% and 83 .33% ,respectively .After the combination of the two features ,the re-sult was exactly the same with the morphologic performance .Conclusion This system performs well in classifying the malignant breast nodule from the benign breast nodule .

Relevance of the expression of CTNNAL1 and the resistance of respiratory tract in rat with airway hyperresponsiveness / 中南大学学报(医学版)

OBJECTIVE@#To observe the relation between the expression of CTNNAL1 and the airway resistance in rats with airway hyperresponsiveness.@*METHODS@#Thirty Wister rats were randomly divided into 5 groups: a normal control group, a 2 d ozone attack group, a 4 d ozone attack group, a 6 d ozone attack group, and a 6 d ozone attack+2 d dexamethasone treatment group (6 rats in each group). The distribution of CTNNAL1 was observed by in situ hybridization; the expression of CTNNAL1 was detected by fluorescence quantitative RT-PCR; the airway resistance was detected in by Buxco pulmonary function analysis system; and the relevance of the expression of CTNNAL1 and the resistance of respiratory tract in rat with airway hyperresponsiveness were analyzed.@*RESULTS@#CTNNAL1 was distributed in bronchial epithelial cells, goblet cells, endothelial cells, and the alveolar wall. With the increase of the ozone attack, the expression of CTNNAL1 mRNA gradually reduced, the airway hyperresponsiveness was aggravated, and the airway resistance was increased.@*CONCLUSION@#During airway hyperresponse, the reduction of CTNNAL1 mRNA can increase the airway resistance. There is a negative correlation between the reduction of CTNNAL1 mRNA and the airway hyperresponsiveness. CTNNAL1 is an adhesion molecule related to airway hyperresponsiveness susceptibility.

Research progress of zebrafish used in drug metabolism / 药学学报

Zebrafish is widely used as a model organism in the process of drug discovery. It expresses drug metabolizing enzymes like cytochrome P450 (CYP450), uridine 5'-diphospho-glucuronosyltransferase (UGT) and nuclear receptors like pregnane X receptor (PXR), aryl hydrocarbon receptor (AHR), etc. This article summarized the profiles of main drug metabolizing enzymes and nuclear receptors, and reviewed the advances on xenobiotics metabolism in zebrafish.

Phaeohyphomycosis caused by Cladosporium sphaerospermum: a case report / 中华皮肤科杂志

A 53-year-old male patient was admitted to the hospital on March 26, 2006. Ten years prior to the presentation, a small furuncle developed on the dorsum of his right hand, and subsided after 2-week treatment with erythromycin ointment; one month later, a broadbean-sized cutaneous ulcer developed on the dorsum of the same hand. After anti-infective treatment, the ulcer healed while the lesional skin thickened, and long-term topical treatment with compound dexamethasone acetate cream showed no obvious effect Dermatological examination revealed an irregular verrucous plaque measuring 2.5 cm × 4 cm with little exudation on the dorsum of the right hand. KOH preparation of the skin lesion revealed brown spores. Sabouraud's dextrose agar culture grew restricted, velvety and dark green colony, and microscopy revealed branched, globular conidiophores generated by cladospores. DNA sequencing showed that the isolate was different from Cladosporium sphaerospermum (AB100654) by 2 bases in the sequence of D1/D2 region of 26S rDNA, from Cladosporium sphaerospermum (AY625063) by 5 bases in the sequence of internal transcribed spacer 1 and 2 (ITS 1 and ITS 2), but fully consistent with Cladosporium sphaerospermum (AM 176719) in the sequence of ITS region. The isolate was identified as Cladosporium sphaerospermum. Hematoxylin-eosin stain of the lesional tissue revealed granulomatous changes,and PAS stain demonstrated brown spores. A diagnosis of phaeohyphomycosis was made. Antifungal susceptibility testing indicated that the isolate was highly sensitive to itraconazole. The lesion obviously subsided after treatment with oral itraconazole 0.2 g once daily for 8 weeks, but the patient was lost to follow up 2 months later.

Progress of zebrafish applied to kidney research / 国际儿科学杂志

As a kind of new model organisms,zebrafish attracts more and more scientists'attention.Because the nephrogenesis and much of kidney disease in zebrafish are similar to those in mammalian,many genes in both kidneys are conserved,and zebrafish has the more simple pronephron,which is convenient to operation and observation.The fish pronephron has been generally applied to study the development and disease of mammalian kidney.This review will focus on recent progress in applying the zebrafish pronephrons to issues of human health and development.

Multiplex RT-PCR assay for the detection of 8 kinds of respiratory viruses / 中华检验医学杂志

. Conclusions Two multiplex RT-PCR assays show high consistency with common RT-PCR. The multiplex RT-PCR assays were initially established.

Laboratory detection on severe acute respiratory syndrome / 中华检验医学杂志

Objective To provide scientific evidence to identify and confirm severe acute respiratory syndrome (SARS) by laboratory detection.Methods Multiple clinical specimens were collected serially and systematically from the 4 suspected SARS patients, which occurred between Dec.2003 to Jan.2004 in Guangdong Province. The samples were tested by serologic and molecular methods.Results IgM or IgG antibodies against SARS-CoV were detectable after 6—8 days of the onset in four patients. The four-fold or greater rising in antibodies was clearly detected in three of the four patients, while the fourth patient’s seroconversion was from negative to positive. The results analysed by enzyme-linked immunosorbent assay( ELISA), immunoflourescence assay (IFA), and neutralization test were highly correlated. SARS-CoV RNA was just detected in 3 throat swab specimens from case 1 by real-time PCR. M, N and S genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR) from the positive samples. Sequencing results showed that they were SARS-CoV gene segments, and most closely matched SARS-CoV gene sequences were isolated from civet cats in Guangdong Province. Nevertheless, SARS-CoV was not isolated from any samples of the 4 patients.Conclusion Based on these results, the 4 reported cases were laboratorily confirmed as SARS cases.