L-amino acid transporter 1 ( LAT1) is a member of L-amino transporter family and an important heterodi?meric amino acid transporter that belongs to subfamily of SLC7. LAT1 mainly mediates trans-membrane transportation of those neutral amino acids that had cyclobenzene or long side chains with high molecular mass such as L-Leu, L-Met and L-Phe as well as some amino acid analogues such as melphalan, L-DOPA and thyroxine in a Na+and ATP-independent diffu?sion. As LAT1 was abnormally overexpressed in various transformed cell lines, it might be related with tumor stage and prog?nosis. It is not only a biomarker that specifically expressed in some tumor cells but also plays an important role in tumor diag?nosis and therapy. Here we demonstrate the structure of LAT1 and its mechanism in transport peculiarity. We also reviewed the development of LAT1 in tumor diagnosis and treatment.

Objective To evaluate 99Tcm-Arg-Glu-Ser (99Tcm-RES) as a potential tumor imaging agent. Methods RES was synthesized using solid phase peptide synthesis. The optimal labeling conditions of RES were determined under different reagents and reacting temperatures using SnC12 as reducing agent.The biodistribution of 99Tcm-RES was studied in nude mice bearing human lung cancer A549. Results The radiochemical purity of 99Tcm-RES was up to 85% and the radiochemical purity was 75% ever after 6 h at room temperature. The tumor uptake of 99Tcm-RES was obvious and the radioactivity ratios of tumor/blood,tumor/heart, tumor/liver, tumor/lung, tumor/spleen and tumor/muscle were 5.31, 1.88, 1.57, 3.58,4. 16 and 5.92, respectively at 6 h after 99Tcm-RES injection. Gamma camera imaging showed that tumor uptake of 99Tcm-RES was negative in rabbits with inflammatory mass but positive in those bearing tumor.The radioactivity ratio of tumor/inflammation was 3.12 at 6 h after injection. Conclusion 99Tcm-RES might possibly become a potential tumor imaging agent.

OBJECTIVESince the outbreak of a highly contagious new pneumonia, atypical pneumonia or severe acute respiratory syndrome (SARS) occurred in Guangzhou area, 33 children with this syndrome were treated in the authors' hospital. The present study aimed to understand clinical characteristics and prognosis of pediatric SARS patients in Guangzhou area.

METHODSClinical manifestations, laboratory and radiologic findings, therapeutic approaches and prognosis of the 33 children with SARS in Guangzhou area were analyzed.

RESULTSOf the 33 cases, 17 were males and 16 were females. The age was between 3 months to 13 years, and 3 - 12 years old patients accounted for 82%. Five (15%) cases had an evident history of contacting SARS patient before the symptoms occurred. Another 5 (15%) cases had a history that contacts of these patients (family members or friends) developed fever and/or cough later. The most common symptoms in this cohort were fever (100%) and cough (91%). Most of the cases had high fever, higher than 39 degrees C. Near half of the cases had nonproductive cough. The initial blood cells count showed that total white blood cell (WBC) count was (2.5 - 9.7) x 10(9)/L. In 22 (67%) cases the WBC count was < 5.0 x 10(9)/L, and in 10 (30%) WBC was (5.0 - 7.0) x 10(9)/L, in 18 cases most of the WBC were lymphocyte count. Chest radiograph showed patchy infiltrates, in 15 cases the changes were unilateral, and in 18 were bilateral. The radiologic changes developed fast, in some cases the changes progressed from one side to both sides. The opacity was absorbed slowly, significant absorption took in average two weeks. Elevated ALT was found in 3 cases and elevated CK-MB in 2 cases. Treatment included isolation, good ventilation of the ward, bed rest, supportive regimens, low volume oxygen inhalation, use of Chinese traditional medicine, antibiotics to prevent bacterial infection, and anti-inflammation therapy. All the patients recovered and discharged from hospital after a mean period of 10.0 +/- 3.8 days.

CONCLUSIONSARS in children may have its own characteristics. The main clinical manifestations were high fever and cough while no severe toxic symptoms, nor respiratory failure was seen; few symptoms or signs suggesting involvement of systems other than respiratory system were seen. Chest radiograph showed uni- or bilateral asymmetric air-space infiltrates which could worsen quickly and were absorbed slowly. Though there were severe changes in the lung, the patients might not have corresponding symptoms or signs. The total white blood cell count in peripheral blood did not increase. All the patients studied had a favorable outcome after the combined treatment.

Adolescent ; Anti-Bacterial Agents ; therapeutic use ; Bed Rest ; Child ; Child, Preschool ; China ; Cohort Studies ; Cough ; complications ; Female ; Fever ; complications ; Humans ; Infant ; Length of Stay ; Lung ; drug effects ; microbiology ; pathology ; Male ; Prognosis ; Severe Acute Respiratory Syndrome ; complications ; diagnosis ; therapy ; Treatment Outcome

OBJECTIVETo investigate the expressions of stathmin gene and its coding protein in laryngeal squamous cell carcinoma, and to explore the relationship between stathmin gene and the biological behaviors of laryngeal squamous cell carcinoma for understanding the tumorigenicity and development of laryngeal squamous cell carcinoma.

METHODSLaryngeal carcinoma tissues (studying group) in the tumors center and laryngeal normal tissues (control group) parted from 1.0 cm of the safe borderline of the tumors were took from 38 patients with laryngeal squamous cell carcinoma while they were in operation. Semiquantitative method of reverse transcriptase polymerase chain reaction (RT-PCR) was used to analyze the expression level of stathmin mRNA, and immunohistochemical staining (frozen section) was used to detect the expressions of stathmin protein, in laryngeal carcinoma tissues and laryngeal normal tissues of 38 cases, respectively.

RESULTSmRNA of stathmin gene was all positively expressed in laryngeal carcinoma tissues and in laryngeal normal tissues of 38 cases by RT-PCR. However, stathmin mRNA was obviously overexpressed in laryngeal carcinoma tissues than that in laryngeal normal tissues (t = 9.655, P < 0.05). Immunohistochemical staining showed stathmin protein was positively expressed in laryngeal carcinoma tissues of 26 cases (26/38, 68.4%), and mild-positively expressed in laryngeal normal tissues in 13 cases (13/38, 34.2%). There was significant difference between the expression rate of stathmin protein in laryngeal carcinoma tissues and in laryngeal normal tissues (chi2 = 8.901, P < 0.05). Meanwhile, the expression level of stathmin mRNA and the positive-expressed rate of stathmin protein in laryngeal carcinoma tissues of the advanced stage patients group (III stage and IV stage) were significantly higher than these in laryngeal carcinoma tissues of I and II stage patients group (t = 6.284, chi2 = 5.810, P < 0.05), and they were also significantly higher in laryngeal carcinoma tissues of the patients group with cervical lymph node metastasis than in laryngeal carcinoma tissues of the patients group without cervical lymph node metastasis (t = 9.350, chi2 = 6.923, P < 0.05).

CONCLUSIONSThe expression levels of stathmin gene and protein were significantly higher in laryngeal squamous cell carcinoma than these in laryngeal normal tissues, the levels are also significantly higher in advanced stage patients group (III stage and IV stage) than in the early stage patients group (I and II), and they are also related to the cervical lymph node metastasis of carcinoma. Stathmin gene may play an important role in the pathogenesis and development of laryngeal carcinoma and may be related to its prognosis.

Adult ; Aged ; Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; pathology ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Stathmin ; genetics ; metabolism

BACKGROUNDScreening libraries against a molecular target in vitro are idealized models that cannot reflect the real state in vivo where biomolecules coexist and interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a unique noninvasive approach to trace a large number of compounds in vivo.

METHODSThe C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin using iterative and pooling protocol. Technetium (V) oxo core [TcO(3+)] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form a library of 8000 (99m)Tc tripeptoid complexes. The radiocombinatorial screening (RCS) in vivo was carried out on SD rats and A549 tumour bearing mice.

RESULTSSignals of tissue distribution and metabolism of libraries were recorded by counting or imaging and tissue targeting leads identified by both random and directed RCS. Among them, (99m)Tc RPA, (99m)Tc VIG and (99m)Tc RES had specific tissue targeting in kidney, liver and tumour respectively. The percent injected dose per gram tissue of (99m)Tc labelled leads in their target tissue was highly structure dependent. Because the nontarget tissue binding and the metabolism of (99m)Tc tripeptoid sublibraries were simultaneously monitored successfully by RCS, the interference of background activity was limited to the lowest level. Optimization of renal function agent from the labelled libraries was carried out by directed screening. (99m)Tc DSG was finally identified the most promising agent for renal function studies.

CONCLUSIONSRCS in vivo is a powerful tool for the discovery of tissue targeting drugs. The potential screening bias is probably the major limitation of labelled libraries.

Animals ; Combinatorial Chemistry Techniques ; Drug Design ; Female ; Isotope Labeling ; Kidney Function Tests ; Liver ; diagnostic imaging ; Mice ; Mice, SCID ; Neoplasms, Experimental ; diagnostic imaging ; Peptide Library ; Radionuclide Imaging ; Radiopharmaceuticals ; chemical synthesis ; Rats ; Rats, Sprague-Dawley ; Technetium ; Tissue Distribution

OBJECTIVE: To review the surgical treatment for reconstructing hypopharynx and cervical esophagus after hypopharyngo-oesophagectomy, and to evalue its efficacy. METHODS: Different methods were adopted to reconstruct the hypopharynx and cervical esophagus among 25 cases, including 14 cases of carcinoma of the hypopharynx and 11 of carcinoma of hypopharynx and cervical esophagus. In accordance with the standard of the International Union Against Cancer in 1997, the 25 cases were divided into different clinic stages, among which 5 were in T(2)N(0), 2 in T(2)N(1), 4 in T(3)N(0), 3 in T(3)N(1), 7 in T(4)N(1) and 3 in T(4)N(2). Treatment protocol was as follow: Pure operation for 5 cases, re-operation after radiotherapy for 2 cases, operation plus radiotherapy for 18 cases, laryngeal conservation operation for 8, and neck dissection for 21 cases. Reconstruction was done by using free jejunal transplantation, gastric pull-up, the laryngotracheal flap, and myocutaneous flap. RESULTS: After the reconstruction, 3 cases of free jejunal graft and gastric pull-up, 4 of laryngotracheal flap recovered oral fleeding within 2 weeks. No serious complications occurred. After 18 cases underwent the myocutaneous flap reconstruction, no complications occurred in 10 patients, but there were different complications in 8 cases, including pharyngocutaneous fistula (6 cases), haryngoesphageal stenosis (7 cases), and pectoralis major myocutaneous flap necrotic (1 case). The 3-year survival rate was 38.9% (7/18). CONCLUSION Reconstruction with free jejunal graft, gastric pull-up, and laryngotracheal flap constitutes is a safe and reliable method to restore the continuity of the upper digestive tract after pharyngo-laryngo-oesophagectomy. After the reconstruction with myocutaneous flap, there is high incidence of pharyngocutaneous fistula and haryngoesophageal stenosis.
Adult ; Aged ; Carcinoma, Squamous Cell ; surgery ; Esophageal Neoplasms ; surgery ; Esophagoplasty ; methods ; Esophagus ; surgery ; Female ; Humans ; Hypopharyngeal Neoplasms ; surgery ; Hypopharynx ; surgery ; Jejunum ; transplantation ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps

This research is launched to look for the medication rules and characteristics of Tibetan medicine in the treatment of gZav-Grib( apoplexy sequelae). HIS records of gZav-Grib patients were selected from the Tibetan Hospital of Tibet Autonomous Region and Tibetan Hospital of the city of Naqu. SPSS Modeler,Gephi and other data mining and visualization software were used to study the actual law of drug use in the treatment of gZav-Grib in Tibetan medicine. Finally,479 cases of gZav-Grib patients in Tibetan medicine were included. Their average age is 63 and average hospital stay was 32 days. In total,82 Tibetan medicine prescriptions were used for treating gZav-Grib. The frequency in the front is Twenty-flavor Chenxiang Pills( 338 times),Ruyi Zhenbao Pills( 322 times),and Seventy-flavor Zhenzhu Pills( 315 times). According to the regularity of Tebitan medicine,they were applied in different time periods including the early morning,morning,noon,and evening,for example,in the early morning: Seventy-flavor Zhenzhu Pills,morning: Ruyi Zhenbao Pills,noon: Eighteen-flavor Dujuan Pills,evening: Twenty-flavor Chenxiang Pills. In the clinical joint,18 groups were found in the 10% support and 70% confidence. There are two prescriptions confidence more than 80% which nature focus on Gan,Ruan,Xi,Liang,Dun,Han,Wen. gZav-Grib of Tibetan medicine can be divided into two types: r Lung-Grib type and k Hrag-Grib type,in which the medicine of r Lung-Grib type takes Seventy-flavor Zhenzhu Pills as the core prescription,while the medicine of k Hrag-Grib type takes Ruyi Zhenbao Pills as the core prescription. It is found that the treatment of gZav-Grib by Tibetan medicine is mainly dominated by the treatment idea about " Therapeutic r Lung and blood,Consideration of venous diseases". Treatment functions is promoting the circulation of Qi,clearing blood heat and getting rid of bad blood,achieving the purpose of treating both principal secondary aspect of gZav-Grib. The research methods based on the HIS can't only optimize the Tibetan treating gZav-Grib sequela treatment plan and rule of medication,but also provide the scientific basis for Tibetan medicine treat gZav-Grib.
Data Mining ; Humans ; Medical Records ; Medicine, Tibetan Traditional ; Software ; Stroke ; complications ; drug therapy ; Tibet

Bentysrepinine (Y101), a derivative of phenylalanine dipeptide, is a novel drug candidate for the treatment of hepatitis B virus (HBV) infection. Our previous preclinical pharmacokinetic study showed that its in vivo absorption and distribution characteristics were probably related to transmembrane transport after Y101 was administered intragastically in rats. In this study, Caco-2 and MDCK-MDR1 cell models were used to investigate interactions between Y101 and P-gp through the apparent permeation coefficient (P_app) and efflux ratio (R_E); the results showed that Y101 was a substrate of P-gp. In addition, gene-transfected cell models, HEK293-hOATP1B1, HEK293-hOATP2B1 and CHO-PEPT1 were used to evaluate the affinity to OATP1B1,

Objective: To analyze the clinical characteristics, treatment and prognosis of Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in children. Methods: A retrospective analysis was performed on the clinical features, laboratory tests, neuroelectrophysiological examination, imaging, treatment and outcomes of 13 patients with Hashimoto's encephalopathy presenting with isolated cerebellar ataxia, who were admitted to the Department of Pediatric Neurology of Guangzhou Women and Children's Medical Center from January 2016 to May 2021. Results: Among the 13 cases, 6 were males and 7 were females. The onset age was 2.6 (2.0,3.3) years, 9 children had precursor infection or vaccination before the first course of disease. All the 13 children had gait abnormalities or unsteady sitting, 10 had intentional tremor, 6 had dysarthria, 3 had body tremor, 2 had nystagmus, 3 had fatigue, 3 had hypotonia, 2 had vomiting and 1 had irritability. Thyroglobulin antibody (TgAb) was 500.0 (298.9,587.2) kU/L and thyroid peroxidase antibody (TPOAb) was 621.9 (449.6,869.4) kU/L in 13 cases. Autoantibodies were positive in 9 cases, and cerebrospinal fluid leukocytosis was seen in 4 cases. Regarding electroencephalography result, 4 cases had background slowing and 1 case had occasional sharp waves. Among the 3 patients who had relapses, 1 had cerebellar atrophy shown on cranial magnetic resonance imaging (MRI) during the recurrence. All the patients received intravenous immunoglobulin (IVIG) and intensive methylprednisolone therapy during the first onset, followed by the disappearance of the symptoms, 1 patient had repeated episodes which was decreased after immunosuppressive treatment with Rituximab.Followed up for 25.0 (22.5,33.3) months after the last episode, 12 achieved complete remission and 1 had a wide base gait. Conclusions: Trunk ataxia is the common symptom of Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in children.Children with cerebellar ataxia should be tested for TgAb and TPOAb to detect Hashimoto's encephalopathy, avoiding missed diagnosis and treatment delays; IVIG and intensive steroid therapy is effective, and immunosuppressive therapy for patients with multiple relapses could reduce the recurrence.
Autoantibodies ; Cerebellar Ataxia ; Child ; Encephalitis ; Female ; Hashimoto Disease ; Humans ; Male ; Retrospective Studies

Bentysrepinine (Y101), a derivative of phenyalanine dipeptide, has a novel mechanism in the treatment of hepatitis B virus (HBV) infection with a good anti-HBV effect. In the present study, a fluorometric-based high throughput method using cytochrome P450 (CYP) screening kit was adopted to evaluate in vitro inhibition potential of Y101 on CYP isoenzymes by calculating remaining enzyme activities and inhibitory potential (IC₅₀ values) using the determined values of fluorescence intensity. The result showed that Y101 exhibited little activity in the inhibition of CYP1A2, CYP3A4, CYP2C9, CYP2C19 and CYP2D6 (IC₅₀ > 100 μmol·L^-1). Y101 was used to treat human primary hepotocytes for 72 h, and the enzyme activities of CYP1A2, CYP2B6 and CYP3A4 were determined with a cocktail of probe substrates for the three CYP isoforms. The metabolites were simultaneously determined using a LC-MS/MS method. Y101 had no activity in the induction of CYP1A2, CYP2B6 and CYP3A4 on the basis of the following results:① The ratio of enzyme activities between test and control groups were all below than 1 (varied from 0.662 to 0.928); ② The induction potential of Y101 were lower than forty percent compared with that of positive groups. The above results suggest that Y101 has little activity in the regulation of metabolic drug-drug interactions based on the CYP isoform changes following co-administration of drugs.