Adult ; Female ; Hematometra ; pathology ; Humans ; Uterine Neoplasms ; pathology ; Uterus ; pathology

Objective To compare the anthelmintic effect of albendazole with that of triclabendazole against Fasciola giganti-ca. Methods Two patients infected with Fasciola gigantica were investigated,and one was administered with albendazole orally (200 mg,twice per day for 5 days)and another was administered with triclabendazole[10 mg/(kg?d)for 2 days]. Their total fe-ces were collected daily during the period of whole therapy,and the eggs of the parasite were collected by using the nylon bag method,and incubated at 28℃. Results The parasite eggs were detected from the first patient’s dejecta on the 1st,2nd and 5th day after the end of the treatment,and no miracidiums hatched out as well as no eggs developed during the period of 25 days of the incubation. Meanwhile,her body temperature fluctuated between 37.4℃and 38.3℃,and she still complained bellyache. For the other invalid,the eggs were not detected on the 2nd and 5th day after the end of the treatment. However,the eggs before and dur-ing the treatment developed the miracidiums of Fasciola gigantica on the 13th day after the incubation,but the eggs collected from the 1st day after the termination of the therapy did not develop and no miracidiums hatched out. At the same time,the signs and symptoms of the patient vanished after the 4th day of the end of the therapy. Conclusions Albendazole has no obvious insecticid-al activity on adult Fasciola gigantica in the short term,but may affect the development of eggs. Triclabendazole has the anthelmin-tic effect on the adults as well as eggs of Fasciola gigantica. In addition,triclabendazole has the characteristics of well curative ef-fect,short course of treatment,and no obvious side effects.

BACKGROUND:Currently, there is a lack of efficient, non-invasive way to transplant stem cels to the target organ or tissue. Exploring a way to guide targeting transplantation of stem cels and to improve the efficiency of stem cel homing is now one of focuses in the field of stem cels research.
OBJECTIVE: To establish a simple and feasible method to chemicaly modify the cel surface using biotin-streptavidin reaction system, and to evaluate the efficiency of this method to label bone marrow mesenchymal stem cels (BMSCs) and its effects on cel biological functions.
METHODS: Passage 3 BMSCs were obtained by whole bone marrow culture method and verified by flow cytometry. Biotin, streptavidin, sulfonated biotin-N-hydroxy-succinimide were used to equip the adhesion molecule ligand, sialyated LewisX (SLeX), to the BMSCs surface. The labeling rate of BMSCs was assessed using fluorescence microscope, the vitality of BMSCs was evaluated by trypan blue staining, and the proliferation of BMSCs was evaluated by cel counting kit-8 assay. Adipogenic and osteogenic inductions were used to evaluate the effect of the method on the multi-differentiation function of BMSCs.
RESULTS AND CONCLUSION: After culture for 2 weeks, passage 3 BMSCs were obtained and confirmed by expressing CD90, CD29 and lack of CD34, CD45. Biotin, streptavidin, sulfonated biotin-N-hydroxy-succinimide were successfuly used to equip sialyated LewisX (SLeX) to the BMSCs surface and had minor effects on the vitality, proliferation, and differentiation of BMSCs. This method was simple for surface modification and had a high modification rate of 88%. The homing of BMSCs modified by this method to the target organ or tissue could be greatly enhanced. Therefore, this method potentialy could have extensive and important applications.

Objective To establish an animal model of high-iodine and low-protein in Wistar rats,and to observe the effect of combined excess-iodine and low-protein diet on growth,metabolism and morphological changes in thyroid.Methods According to body weight[(110 ± 10)g] and sex(half male and half female),one hundred and ninety-two Wistar rats,1 month after weaning,were randomly divided into ① normal iodine control group (NI),② 10-fold excess-iodine group (10HI),③ 50-fold excess-iodine group (50HI),④ 100-fold excess-iodine group (100HI),⑤ low-protein control group (LC),⑥ low-protein and l 0-fold excess-iodine group (L10HI),⑦low-protein and 50-fold excess-iodine group (L50HI),⑧ low-protein and 100-fold excess-iodine group(L100HI).Twenty-four rats were in each group,with the experimental period of 6 months.The iodine content of NI and LC groups was 4.65 μg/d; 10HI,50HI and 100HI groups were 46.50,232.50 and 465.00 μg/d,respectively.The animal's body weight,water and feed consumption were recorded weekly.At the end of 60,120,180 days,urine and blood samples were collected from eight rats in each group.Urinary iodine was tested by arseni cerium catalytic spectrophotometry; serum iodine was tested by the method of chloric acid.Histological change of the thyroid gland was observed by transmission electron microscopy and hematoxylin-eosin (HE) staining at the end of 6 months; apoptosis of thyroid was tested by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method.Results At the end of 4,8,16,18,22 and 24 weeks,the differences of body mass of rats among groups were statistically significant(F =4.26,3.75,4.98,4.09,3.28,3.95,all P ＜ 0.05).At the end of 60,120,180 days,the differences of iodine concentration in urine and blood among groups were statistically significantly (H =5.37,6.03,all P ＜ 0.05).Light microscopy showed that thyroid follicular epithelial cells became flattened,and follicles became distended with colloid following increasing of iodine concentration.Electron microscopy showed increased glial vesicles,condensation of nuclear chromatin,karyopyknosis,and karyolysis with increasing of iodine concentration.The differences of apoptotic indexes among groups were statistically significant (F =4.59,P ＜ 0.01).The apoptotic indexes of L50HI and L100HI groups [(21.50 ± 5.20)‰,(26.70 ± 6.40)‰] were higher than those of 50HI and 100HI groups [(11.20 ± 4.30)‰,(19.40 ± 4.80)‰,P ＜ 0.01 or ＜ 0.05].Conclusion Excessiodine and low-protein can cause growth retardation,abnormal iodine metabolism,and thyroid follicular epithelium damage in Wistar rats.

Aim To study the pharmacokinetics characteristics of galanthamine hydrohromide sustained release tablets and conventional tablets in healthy volunteers after a single and multiple oral doses. MethodsA single and multiple oral doses of galanthamine hydrohromide sustained release tablets and conventional tablets were given to 20 healthy male volunteers in a randomized cross-over study. We developed an LC-MS assay using naloxone as the internal standard to determine the plasma concentrations of galanthamine, calculate the pharmacokinetic parameters and evaluate the relative bioavailability and sustained release characteristics of galanthamine hydrohromide sustained release tablet. Results The pharmacokinetic parameters of the sustained release tablet and conventional tablet obtained from the single-dose study were as follows: the HVD_12 C_max(time span during which the plasma concentration is at least half of the C_max value)were (15.4?1.7) h and (5.4?2.5) h, the retard quotients (R△,the HVD_12 C_max ratio of sustained release tablets to conventional tablets) of sustained release tablet was 3.4?1.4, the T_max were (4.4?1.5) h and (1.3?1.2) h, the C_max were (27.5?2.9) ?g?L-1 and (53.7?12.7) ?g?L-1.Results showed significant sustained release characteristics of the sustained release tablet. The relative bioavailability of the sustained release tablet was (95.9?14.2) %。The pharmacokinetic parameters of the sustained release tablet and conventional tablet obtained from the multi-dose study were as follows: the T_max were (3.0?1.6) h and (0.9?0.3) h,the CSS_max were (58.8?9.4) ?g?L-1 and (52.0?6.9) ?g?L-1,the CSS_min were (16.2?4.0) ?g?L-1 and (22.5?5.0) ?g?L-1,the C_av were (39.0?3.9) ?g?L-1 and (37.1?5.0) ?g?L-1,the DF were 1.1 ?0.3 and 0.8?0.1, respectively. Results of two one-side t test showed that AUC_SS、CSS_max、C_av of two tablets were bioeqivalent. Conclusion Results showed that the sustained release tablet and the regular tablet were bioequivalent in absorbed extent, and the sustained release tablet exhibited a good retarding effect in release.

Objective To establish the quantitative detection of capsule associated protein 10 (CAP10)and virulence-associated DEAD-box RNA helicase 1(VAD1)genes in Cryptococcus neoformans (CN) and compare the diagnostic values of single gene test and combined gene test in CN meningitis.MethodsTwenty-three CN meningitis patients with fungal culture or ink staining or CN antigen detection positive in cerebrospinal fluid (CSF) were recruited and patients with craniocerebral trauma were recruited as controls.Standard plasmids were constructed using standard CN strain.Real time fluorescent quantitative polymerase chain reaction (RT-FQ-PCR) was established to detect the mRNA expressions of CAP10 and VAD1 genes in the CSF of patients with CN meningitis,which were compared with the results of CSF ink staining,fungal culture and antigen detection.The diagnostic values of single gene test and combined gene test were compared by chi square test.Results Among 23 CN meningitis patients,22 (95.6％) were CAP10 mRNA positive detected by RT-FQ-PCR,which was significantly higher than both ink staining (16/23,69.6％,x2 =4.167,P＜0.05) and fungal culture (15/23,65.2％,x2=5.143,P＜0.05),respectively; but not significant different from antigen detection (21/23,91.3％,x2=0.500,P＞0.05).There were also no statistical significant differences between combined detection of CAP 10 + VAD1 and CAP 10 or VAD1 single gene test (P＞0.05).ConclusionRT-FQ-PCR detection is successfully established using virulence genes as target,which is superior to the conventional methods.

Objective To research the clinical significance of acetated Ringer solution and succinylated gelatin in the fluid resuscitation of sepsis patients.Method Fifty-nine sepsis patients were divided into two groups:lactic acid Ringer solution and hetastarch (group A,27 cases)and acetated Ringer solution and suecinylated gelatin (group B,32 cases),compared the fluid resuscitation and other parameter.Results There were no significant difference in the central venous pressure,mean arterial pressure and the dose of noradrenaline (P ＞ 0.05).The activated partial thrombeplastin time in group A was longer than that in group B[(58±10),(74±13)s vs(48±7),(54 ±11) s in 6,24 hours],fibrinogen concentration was lower than that in group B [(3.3 ±0.8),(1.6±0.3)g/L vs (4.2±1.1),(2.1±0.2)g/L in 6,24 hours] (P＜0.05).Serum lactic acid,creatinine,calcium concentration in group A [(6.9±0.8)retool/L,(289 ~ 27)μ mol/L,(2.1 ±0.3)mmol/L]were higher than those in group B [(3.2 ±1.1)mmol/L, (193 ±42)μmol/L, (1.7±0.2)mmol/L](P＜0.05),there was no difference in APACHE Ⅲ scores on the third day between two groups (P＞0.05).Conclusions Acetated Ringer solution and succinylated gelatin in the fluid resuscitation of sepsis patients has the same effect,but fewer impacts on serum coagulation,serum lactic acid and renal function than lactic acid Ringer solution and hetastareh.They may be more suitable for fluid resuscitation of sepsis patients,but hypecalcemia is easy to happen,and there is no significant evidences proving the prognosis.

Acquired Immunodeficiency Syndrome ; diagnosis ; Adult ; Female ; Humans ; Larynx ; pathology

Adult ; Cranial Nerve Neoplasms ; Female ; Humans ; Hypoglossal Nerve ; Paraganglioma

Small molecule covalent inhibitors, or called as irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity. Nevertheless, these agents may also exhibit larger toxicity once off-target effects arise. This "double-edged swords" property often leads drug researchers to avoid attaching them. In recent years, some problems such as drug resistance are difficult to be solved with reversible inhibitors leading researchers to pay more attention on the covalent inhibitors. In this review, we shall make a short summary to the recent research progress of covalent inhibitors and the interaction modes between covalent inhibitors and their target protein residues.
Amino Acids ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; therapeutic use ; Antiviral Agents ; chemical synthesis ; chemistry ; therapeutic use ; Drug Discovery ; Drug Resistance ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Hepatitis C ; drug therapy ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; Protein Binding ; Protein Kinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Serine Proteinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use