Abstract: Objective　To investigate the species distribution and the antifungal susceptibility of fungi originating from positive blood cultures in Guangdong, so as to provide a basis for the rational use of antifungal drugs in clinical fungal bloodstream infections. Methods All data were collected for retrospective study from monitoring units of the Guangdong Fungal Disease Surveillance Network between 2019-2021, including clinical characteristics, species distribution and antifungal susceptibility. Results A total of 3 589 fungi strains were isolated, most of which were Candida spp. (86.5%, 3 105/3 589). The most common species was Candida albicans (36.6%, 1 315/3 589), followed by Candida tropicalis (17.4%, 1 626/3 589) and Candida parapsilosis (14.5%, 520/3 589). There were 42.1%(1 512/3 589) of strains isolated from ICU. The proportions of Candida albicans strains were 40.0%-50.0% among ICU, general surgery, organ transplantation and emergency department. Candida tropicalis (60.0%, 144/240) was the most common species in hematology department. Both Cryptococcus neoformans (35.4%, 69/195) and Talaromyces marneffei (35.9%,70/195) were common in infection department. All of the Candida isolates were of wild-type (WT) phenotype to amphotericin B. Resistance rates of caspofungin and micafungin for Candida spp. ranged from 0.0% to 4.2%. The resistance rates of Candida tropicalis to fluconazole and voriconazole were 42.3% and 38.9%, which were significantly higher than other common Candida spp. The cryptococcus neoformans strains were totally of WT phenotype to fluconazole and voriconazole. Conclusions Candida albicans is the most common species originating from positive blood cultures in Guangdong Province. Common Candida strains are highly sensitive to echinocandins and amphotericin B. Candida tropicalis has a high resistance rate to triazole drugs.

OBJECTIVETo explore the effect of Telbivudine (LDT) Tablet combined with Jianpi Bushen Recipe (JBR) on serum hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL) and HBeAg seroconversion in chronic hepatitis B (CHB) patients.

METHODSTotally 90 HBeAg-positive and human leukocyte antigen (HLA)-A2 positive CHB patients were randomly assigned to the treatment group and the control group, 45 cases in each group. Patients in the treatment group took LDT Tablet (600 mg, once per day) combined with JBR granule (twice per day), while those in the control group took LDT Tablet alone. The therapeutic course for all was one year. HBV DNA negative conversion rate, HBeAg seroconversion rate, and level of HBV specific CTL were compared after 1 year treatment; liver function, drug resistance mutations, and adverse reactions were also compared between the two groups.

RESULTSAfter 1 year treatment, HBV DNA negative conversion rate and HBeAg seroconversion rate were 88.89% (40/45) and 40.00% (18/45) in the treatment group, higher than those of the control group [68.89% (31/45) and 20.00% (9/45)], with statistical difference (P < 0.05). Level of HBV specific CTL in the treatment group was 0.78% +/- 0.09% after treatment, higher than that of the control group after 1 year treatment (0.54% +/- 0.11%) and that before treatment (0.36% +/- 0.07%), with statistical difference (P < 0.01). Level of HBV specific CTL in 27 patients with HBeAg seroconversion was 0.81% 0.10%, higher than that of 63 patients without HBeAg seroconversion (0.60% +/- 0.09%), with statistical difference (P < 0.01). ALT returned to normal in 44 cases of the treatment group (97.78%), while it was 42 cases (93.33%) of the control group, with no statistical difference between the two groups (P > 0.05). Total bilirubin (TBil) in the two groups all turned to normal. rtM204I variation occurred in 1 case (2.22%) of the treatment group and 2 cases (4.44%) in the control group. No obvious adverse reaction occurred in the two groups.

CONCLUSIONLDT Tablet combined with JBR could elevate levels of HBV specific CTL and HBeAg seroconversion in CHB patients.

Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; drug therapy ; Humans ; Seroconversion ; T-Lymphocytes, Cytotoxic ; immunology ; Tablets ; Thymidine ; analogs & derivatives ; therapeutic use

Amino Acids ; analysis ; Animals ; Chromatography, Gas ; methods ; Drug Contamination ; Electrophoresis, Polyacrylamide Gel ; Materia Medica ; chemistry ; Quality Control ; Swallows ; classification

OBJECTIVETo explore the molecular mechanism of exocrine immune inflammatory injury of Sjögren's Syndrome and the intervention of Banxia Qinlian Decoction (BQD).

METHODSTotally 18 female NOD mice were randomly divided into the model group, the positive drug group, and the BQD group, 6 in each group. Six female BALB/c mice were recruited as a blank control group. Mice in the blank control group and the model group were gavaged with deionized water at the daily dose of 0.1 mL/10 g body weight. Tripterygium Tablet was administered by gastrogavage to mice in the positive group at the daily dose of 10 mg/kg. BQD was administered by gastrogavage to mice in the BQD group at the daily dose of 60 g crude drugs/kg. After 12 weeks of medication, mice were sacrificed. Their eyeballs were excised and blood collected. Tissues of bilateral parotids and submandibular glands were kept. mRNA transcriptional levels of IL-17, IL-6, type 3 muscarinic acetylcholine receptors (M3R), aquaporin protein-5 (AQP5) were detected by RT-PCR. Expression levels of M3R and AQP5 protein were detected by Western blot. Protein expression levels of IL-17 and IL-6 were detected by ELISA.

RESULTSCompared with the normal group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly up-regulated in the model group (P < 0.01). Compared with the model group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly down-regulated in the positive drug group and the BQD group with statistical difference (P < 0.01, P < 0.05). Compared with the BQD group, mRNA-transcriptional levels of IL-17, IL-6, and M3R, as well as M3R and AQP5 protein expression levels were significantly down-regulated in the positive drug group (all P < 0.01).

CONCLUSIONThe molecular mechanism of BQD in inhibiting SS exocrine neurotoxic injury might be possibly related to regulating Th17/IL-17 immune inflammatory way.

Animals ; Aquaporin 5 ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Interleukin-17 ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Sjogren's Syndrome ; drug therapy ; immunology ; Submandibular Gland ; Th17 Cells ; Up-Regulation

BACKGROUNDSimultaneous pancreas-kidney transplantation (SPKT) frees the diabetic patient with end-stage nephropathy from dialysis and daily insulin injections. Herein, we review consecutive cases of SPKT with bladder drainage performed at our institution over an 8-year period.

METHODSThe study population included 21 patients (16 males and 5 females) who underwent SPKT between September 2001 and September 2009. Seven patients had type-1 diabetes and 14 had type-2 diabetes. Nineteen patients were on dialysis at the time of transplantation. Donation after cardiac death donors were selected for SPKT. The mean human leukocyte antigen match was 2 (range 0 - 4). SPKT was always performed using bladder drainage and vascular anastomoses to the systemic circulation. Immunosuppressive treatment consisted of anti-lymphocyte globulin induction followed by tacrolimus, mycophenolate mofetil, and prednisone.

RESULTSThe mean hospital stay was 45.43 days. After a mean follow-up of 39.4 months, survival rates for patient, kidney, and pancreas were 76.2%, 76.2%, and 66.7% at 1 year; 76.2%, 59.3%, and 55.6% at 5 years; and 57.1%, 39.5%, and 41.7% at 8 years, respectively. Major complications included anastomotic leaks, reflux pancreatitis, and rejection. Six patients died from septic shock (n = 3), duodenal stump leak (1), cardiac arrest (1), or renal failure (1). Eight kidney grafts were lost due to acute rejection (n = 2), chronic rejection (3), and death with a functioning graft (3). Pancreatic graft failure (9) was caused by thrombosis (n = 1), rejection (2), duodenal stump leak (1), and death with a functioning graft (5).

CONCLUSIONSSPKT is a valid therapeutic option for uremic diabetics although few hospitals in China can undertake SPKT.

Adult ; Diabetes Mellitus, Type 1 ; surgery ; Diabetes Mellitus, Type 2 ; surgery ; Female ; Graft Rejection ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; adverse effects ; mortality ; statistics & numerical data ; Male ; Middle Aged ; Pancreas Transplantation ; adverse effects ; mortality ; statistics & numerical data ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome ; Urinary Catheterization

Epitopes, T-Lymphocyte ; HLA-A2 Antigen ; immunology ; Hepatitis B Core Antigens ; genetics ; Hepatitis B virus ; genetics ; immunology ; Humans ; Mutation

AIMTo construct short hairpin RNA (shRNA) eukaryotic expression vectors targeting TGF-beta1 for further research on the effects of TGF-beta1 on vasculogenesis and angiogenesis.

METHODSThree pairs of siRNA target sequences coding from the mRNA of TGF-beta1 gene were designed and three pairs of nucleotides were synthesized. After annealing, the double-strand DNA products were ligated into the pEN_mH1c entry vector, and in turn into the shRNA eukaryotic expression vector pDS_hpEy labled by GFP through the LR recombination reaction. After sequencing successfully, the three resulting TGF-beta1 shRNA expression vectors were transfected into the mouse fibroblast cell line (NIH/3T3), and then cell clones stably expressing TGF-beta1 shRNA were screened. Reverse Transcript-Polymerase Chain Reaction (RT-PCR) and Western blot were used to detect the mRNA and protein expression.

RESULTSRT-PCR and Western blot showed that one of the TGF-beta1 shRNA expression vectors pDS_Tc downregulated TGF-pl mRNA and protein expression markedly in NIH/3T3 cells.

CONCLUSIONShRNA eukaryotic expression vectors targeting TGF-beta1 are successfully constructed which can be used for further investigation on the mechanism through which TGF-beta1 regulates vasculogenesis and angiogenesis.

Animals ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; metabolism ; Mice ; NIH 3T3 Cells ; Neovascularization, Physiologic ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Transfection ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVETo study the mechanism of microelement including Cu and Zn on the accumulation of three danshinones in Salviae miltiorrhizae root and build a theory basis for its good quality and high yield.

METHODSand culture experiments were conducted to study the effect of Cu and Zn on the accumulation of three danshinones and oxidase including peroxidase and polyphenol oxidase activity in the plant root. The correlation between available Cu and Zn contents in matrix and oxidase activity in the plant root and, the correlation between available Cu and Zn contents in matrix and contents of tanshinones in the root were discussed.

RESULTContents of danshinones in the root increased with the increasing of Cu and Zn concentration. Dynamic monitoring on contents of dan-shinones of the plant roots growing in the pots with different Cu and Zn concentration in the whole growing season showed that the contents of danshinones for 60 days were the lowest, for 120 days the highest and then dropped for 150 days. In addition, among available Cu and Zn contents of matrix, oxidase including peroxidase and polyphenol oxidase activity and contents of tanshinones in the root,the correlation between two factors were significant difference (P < 0.05 or P < 0.01).

CONCLUSIONThe mechanism of Cu and Zn on the accumulation of danshinones may be that Cu and Zn improve the activity of peroxidase and polyphenol oxidase, which promote transformation of phenolic compounds to terpenes and therefore to increase contents of danshinones.

Catechol Oxidase ; metabolism ; Copper ; metabolism ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; analysis ; metabolism ; Peroxidase ; metabolism ; Phenanthrenes ; metabolism ; Plant Proteins ; metabolism ; Salvia miltiorrhiza ; enzymology ; metabolism ; Zinc ; metabolism

AIM To study the effects of baicalin and gardenoside pairing on 5-lox/CysLTs/CysLT pathway of rats with cerebral ischemia injury.METHODS SD rats randomly assigned into control group,model group,baicalin and gardenoside pairing groups (7 ∶ 3,dosed at 30,45,60 mg/kg,respectively) in their cerebral ischemia recovery period were simulated with permanent middle cerebral artery occlusion (pMCAO) if necessary.After a week of natural recovery,the drugs' pharmacodynamic effects were evaluated by the neurofunctional scoring and HE staining,their impact on the content of CysLTs was determined by ELISA,and the influence on the expression of 5-lox,CysLT1 and CysLT2 was detected by western blot.RESULTS One-week consecutive administration of baicalin and gardenoside pairing contributed to a reduction in infiltration and tissue edema of ischemic cells.If compared with pMCAO group,the baicalin and gardenoside pairing groups were observed with significantly lowered scores of neurologic functioning,inhibited microglia activation,decreased content of CysLTs and down-regulated expression of 5-LOX,CysLT1 and CysLT2 (P ＜ 0.01).CONCLUSION Baicalin and gardenia pairing's alleviating effect to the damage of cerebral ischemia may be associated with its inhibition on microglia activation and 5-lox/CysLTs/CysLT signaling pathway,and thus an inflammatory impairment reduction.

OBJECTIVE Based on the methods of microdialysis,HPLC-MS/MS and gene chip tech-nology,the mechanism of Baicalin and Geniposide(BC/GP)against excitatory amino acid toxicity in ce-rebral ischemia was studied. This will provide guidance for the clinical application of BC/GP and the study of excitatory amino acid toxicity in cerebral ischemia.METHODS (1)Microdialysis technique and HPLC-MS/MS was performed to study the pharmacodynamics of BC/GP against cerebral ischemia. ①18 SD rats with body weight of(280±20)g were randomly divided into control group,treatment groups with BC/CP at low dose,medium dose and high dose(equal to the dosage of crude drugs for 30 mg·kg-1, 45 mg·kg-1and 60 mg·kg-1respectively).Rats in each group were given intragastric administration for seven days to establish cerebral ischemia model. Then, microdialysis probe was applied to collect cerebrospinal fluid from hippocampus before and after cerebral ischemia. ② First, we established the HPLC-MS/MS method for measuring drugs and excitatory amino acids.Then we detected the microdi-alysis samples and observed their changes in animals.(2)The mechanism of BC/GP against excitatory toxicity of cerebral ischemia were observed at gene level by chip technique. ① 16 SD rats with body weight of 240±20 g were randomly divided into sham group, model group, treatment group of BC(60 mg·kg-1),treatment group of GP(60 mg·kg-1)and treatment group of BC/GP(7:3)(60 mg·kg-1).Rats in eachgroup were given intragastric administration for seven days to establish cerebral ischemia model. Then the rats were sacrificed,and the hippocampus were rapidly harvested and stored at-80℃for further detection. ②After the quality inspection of the hippocampal,the qualified samples were subjected to detect the levels of neurotransmitter receptor gene in the ischemic of rats by gene chip technology.Finally,the results were analyzed by the method of Δ ΔCt.RESULTS (1)Only three compounds includ-ed GP,glutamic acid and aspartic acid were detected in microdialysis samples by HPLC-MS/MS.The concentration of GP increased and lasted for 120 min with a significant dose-dependent after cerebral ischemia.Compared with low dose group,the AUC(0-t),MRT(0-∞),Cmaxand t1/2zin high-dose group showed significant difference(P<0.01).Compared with the model group,the levels of glutamic acid and aspartic acid in the treatment groups decreased significantly,especially in the middle and high dose groups.(2) 89 genes in the neurotransmitter receptor gene signaling pathway were detected by gene chip technol-ogy. There were 22 genes with |Fold Regulation|>1.5 in the model group, compared with the sham group.Five of the 22 genes showed statistically significant differences,including Grin2c(2.9026),Chrna7 (-1.5877), and Tacr2 (-1.7695). Htr3a (-1.8172) and Grm6 (-2.3527). There were 5 genes with |Fold Regulation|>1.5 in the BC group, compared with the model group, Two of them exhibited statistically significant differences,including Brs3(1.797)and Grin2c(-1.7979).There were 14 genes with|Fold Reg-ulation|>1.5 in the GP group, compared with the model group. Three of them displayed statistically significant differences,including Hcrtr2 (-1.6584), Sctr (-3.8524) and Grin2c (-4.8408). Compared with model group, the genes of |Fold Regulation|>1.5 in BC/GP (7:3) group are 5, and only one of them showed a significant differences. CONCLUSION (1)After administration of BC and GP,GP can cross the blood-brain barrier and reduce the release of excitatory amino acids in the hippocampus. (2) BC/GP can inhibit the interaction between excitatory amino acids and excitatory amino acid receptors and attenuate the toxicity of excitatory amino acids by down-regulating the expression of glutamic acid receptor Grin2c gene.(3)BC/GP may exert their brain protection effect by reducing the release of excit-atory amino acids and inhibiting the expression of excitatory amino acid receptors.