Small molecule antibodies are naturally existed and well functioned but not structurally related to the conventional antibodies. They are only composed of heavy protein chains or light chains, much smaller than common antibody. The first small molecule antibody, called Nanobody was engineered from heavy-chain antibodies found in camelids. Cartilaginous fishes also have heavy-chain antibodies (IgNAR, "immunoglobulin new antigen receptor"), from which single-domain antibodies called Vnar fragments can be obtained. In addition, free light chain (FLC) antibodies in human bodies are being developed as therapeutic and diagnostic agents. Comparing to intact antibodies, common advantages of small molecule antibodies are with better solubility, tissue penetration, stability towards heat and enzymes, and comparatively low production costs. This article reviews the structural characteristics and mechanism of action of the Nanobody, IgNAR and FLC.
Animals ; Camelids, New World ; immunology ; Humans ; Immunoglobulin Light Chains ; chemistry ; immunology ; Receptors, Antigen ; immunology ; Sharks ; immunology ; Single-Chain Antibodies ; chemistry ; immunology ; therapeutic use ; Single-Domain Antibodies ; chemistry ; immunology ; therapeutic use

OBJECTIVETo analyse the diagnostic and therapeutic aspects of carotid body tumor (CBT).

METHODSSeven patients with CBT had been hospitalized between 2003 and 2006. The clinical data was analyzed retrospectively. The preoperative evaluation included angiography in 7 patients. Most of them had an asymptomatic cervical lateral mass. Only one patient had the hoarseness and buckling and was given radiation therapy alone. Six of seven patients with carotid body tumour underwent surgery. Simple tumor excision was accomplished in 4. Carotid artery resection with the tumor was required in 2 patients and in the both, interposition of a 7 mm polytetrafluoroethylene graft was performed . During the resection, temporary carotid shunt was required in the two patients.

RESULTSAll tumors by surgery were identified as carotid paragangliomas without evidence of malignancy. There was no mortality and no hemiplegia. After surgery, temporary cranial nerve dysfunction was noted in one case. In the follow-up period of 2 months to 2 years, no recurrent disease occurred. The patient's tumor who accepted radiotherapy was in the stable stage under the half year follow up, and the follow up would be further continued.

CONCLUSIONSWith non-invasive investigation and arteriography it was possible to obtain an early and precise diagnosis. The surgical management was the major treatment of these tumors. The pattern of operation should be chosen according to the relation of tumor and carotid. The decision to perform simple tumor excision or additional arterial resection was based on diagnostic preoperative and after the arterial resection the polytetrafluoroethylene graft would be used for carotid reconstruction.

Adult ; Blood Vessel Prosthesis ; Blood Vessel Prosthesis Implantation ; Carotid Body Tumor ; diagnosis ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo study the feasibility and effect of substituting esophagus with stomach or colon without thoracotomy in the treatment of cervical esophageal carcinoma with laryngeal function preserved.

METHODSTwenty-four patients with cervical esophageal carcinoma were retrospectively reviewed. The esophagus was resected and substituted with 19 gastric pull-up and 5 colon interposition. Nineteen patients received radiotherapy postoperatively (dose 50 - 70 Gy).

RESULTSTwenty two patients were follow up over 3 years. The 3- and 5-year survival rates for T2 were 3 and 1, for T3, T4 8 and 3, respectively. The laryngeal function preservation rate was 77% (17/24) and the decannulation rate was 75% (12/16). The complication rate was 29%.

CONCLUSIONSurgical resection of cervical esophageal carcinoma with removal of the extraesophageal invaded tissues while preserving the laryngeal function is possible. The continuity of the esophagus is restored by stomach transposition and colon interposition. Combined with radiotherapy, the survival rate and life quality of the patient might be improved.

Adult ; Aged ; Esophageal Neoplasms ; mortality ; physiopathology ; surgery ; Esophagoplasty ; methods ; Female ; Follow-Up Studies ; Humans ; Larynx ; physiopathology ; Male ; Middle Aged ; Quality of Life ; Survival Rate ; Thoracotomy

OBJECTIVETo review the experience of different surgical construction methods and comprehensive treatments for hypopharyngeal cancer.

METHODSThree hundred and fifty-two cases (According to UICC 2002 criteria, stage I, 3; II, 31; III, 134; IV, 184) with hypopharyngeal cancer were retrospectively reviewed from 1999 to 2005 in the Department of Otorhinolaryngology of Qilu Hospital of Shandong University, including 321 males and 31 females. The median age was 58 years old, ranged from 26 to 82 years old. All the tumors originated from the pyriform sinus (272), posterior pharyngeal wall (61), postcricoid area (19). There were no distant metastasis. Two hundred and fourty-one cases were surgically treated with laryngeal functions preserved and 111 cases without laryngeal functions preserved. All the patients received modified neck dissection, including both unilateral (247 patients) and bilateral (105 patients). Pharyngoesophageal defect reconstruction methods in cases with laryngeal functions preserved were: direct suture in 137, pectoralis major musculocutaneous flap in 62, split graft in 2, pectoralis major musculocutaneous flap combined with the split graft in 5, stomach pulling-up in 12, colon interposition in 23 patients. While in cases without laryngeal functions preserved the methods includes: direct suture in 54, laryngotracheal flap in 54 patients, pectoralis major musculocutaneous flap in 7, laryngotracheal flap combined with pectoralis major musculocutaneous flap in 8, stomach pulling-up in 22, colon interposition in 3 patients. All patients received radiotherapy postoperatively (dose 55 - 75 Gy).

RESULTSThe overall 3 and 5 year survival rates were 65.1% (229/352) and 53.6% (142/265), respectively. For stage I, the 5 year survival rate was 3/3, stage II, 80.6%(25/31), stage III, 65.0% (67/103), stage IV, 36.7% (47/128). The 3 and 5 year survival rates in functionally preserved group were 68.0% (164/241) and 59.7% (114/191), respectively, while in non-functionally preserved group were 58.6% (65/111) and 37.8% (28/74), respectively. The cervical lymph node metastasis was found in 239 sides. Pathologic findings showed that well, moderately and lower differentiated squamous cell carcinomas were 84, 163, 105 cases, respectively. Laryngeal functions (voice, respiration and deglutition) were completely restored in 169 patients and partially restored (voice and deglutition) in 72 patients.

CONCLUSIONSCombined surgery and radiotherapy are the best choice for hypopharyngeal cancer. The continuity of the pharyngoesophagus is restored and the laryngeal function is preserved as far as possible. The preservation of laryngeal function and the laryngeal and pharyngeal reconstruction are based on the premise that the tumor was excised completely.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; therapy ; Combined Modality Therapy ; Female ; Humans ; Hypopharyngeal Neoplasms ; therapy ; Laryngectomy ; Male ; Middle Aged ; Pharyngectomy ; Retrospective Studies

OBJECTIVECanine model established for tracheal defect reconstruction, to investigate the outcome of tracheal reconstruction with combination of polypropylene and flap.

METHODSAbout 3.5 to 4 centimeter cervical trachea was resected and replaced with artificial trachea made from monofilament knitted polypropylene and surgical flap. Covered stent was implanted postoperatively. Survival period and quality of life were recorded, bronchofibroscopy, X-ray films and HE sections were performed.

RESULTSSix dogs survived well and another two died. The causes of death were respiratory failure in 1 and infection in another. Stenosis of anastomosis in 1 was recorded during survival period. The dogs started drinking and eating on the second postoperative day, no dyspnea was found. The animals were sacrificed at 2, 4, 8 weeks and 6 months after surgery. Soft tissue growth was found in polypropylene net 2 weeks after surgery and more at 4 weeks. The polypropylene net was covered completely with soft tissue at 8 weeks and 6 months postoperatively, the hardness and sustentation degree were enhanced following the growth and fibrosis of soft tissue. The squamous epithelium and columnar epithelium were observed healing well by HE staining method.

CONCLUSIONSOne-stage operative artificial trachea made from monofilament knitted polypropylene which has good histocompatibility and surgical flap is the closer artificial trachea to native trachea. It has a promising prospect in clinical use.

Animals ; Dogs ; Polypropylenes ; Prostheses and Implants ; Reconstructive Surgical Procedures ; instrumentation ; methods ; Skin Transplantation ; Surgical Flaps ; Trachea ; surgery

OBJECTIVETo review the experience of different surgical construction methods for hypopharyngeal cancer with cervical esophageal invasion.

METHODSFrom 1989 to 2000,forty-eight patients with advanced hypopharyngeal cancer and cervical esophageal invasion were retrospectively reviewed, including 38 males and 10 females. The median age was 54. 3 years old, ranged from 26 to 71 years old. According to UICC 1997 criteria, all the tumors were T4 stage and originated from the pyriform sinus (33), posterior pharyngeal wall (14), postcricoid area (1), there were 28 patients in cN0, 15 in cN1, 5 in cN2 and no distant metastasis. Precise preoperative evaluation was performed with computed tomography scan, barium swallow perspective and biopsy. All the patients received modified neck dissection, including both unilateral (38 patients) and bilateral (10 patients). Pharyngoesophageal defect reconstruction methods were: laryngotracheal flap in 11 patients, pectoralis major musculocutaneous flap in 13, laryngotracheal flap combined with pectoralis major musculocutaneous flap in 6, pectoralis major musculocutaneous flap combined with the split graft in 10, stomach pulling-up in 3, colon interposition in 5 patients. Total laryngectomy was carried out in 8 patients. All patients received radiotherapy postoperatively (dose 55 - 75 Gy).

RESULTSThe cervical lymph node metastasis was found in 20 patients. Pathologic findings showed that well, moderately and lower differentiated squamous cell carcinomas were 18, 24, 6 cases, respectively. The overall 3 and 5 year survival rates were 52.1% (25/48) and 27.3% (12/44), respectively. The 3 and 5 year survival rates in functionally preserved group were 65.2% (15/23) and 33.3% (7/21), while in non functionally preserved group were 40.0% (10/25) and 21.7% (5/23), respectively. Fifteen patients laryngeal functions (voice, respiration and deglutition) were completely restored and 8 patients partially restored (voice and deglutition). The decannulation rate was 65% (15/23). The complication included pharyngeal fistulas in 10 cases and splitting of chest wall in 1 cases.

CONCLUSIONSCombined therapy was the best choice for hypopharyngeal cancer with cervical esophageal invasion. The laryngeal function is preserved as far as possible. The continuity of the pharyngoesophagus was restored by pectoralis major musculocutaneous flap, laryngotracheal flap, or combined with the split graft. Stomach transposition or colon interposition was used while the defect of the esophagus was greater.

Adult ; Aged ; Carcinoma, Squamous Cell ; mortality ; pathology ; surgery ; Esophageal Neoplasms ; mortality ; secondary ; surgery ; Esophagus ; pathology ; Female ; Humans ; Hypopharyngeal Neoplasms ; mortality ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate

OBJECTIVEBrugada syndrome is an inherited channelopathy that characterized by ST-segment elevation in the right precordial lead (V(1)-V(3)) on the electrocardiogram with or without right bundle branch block and related with high risk of sudden cardiac death and structurally normal hearts. The first and only gene linked to this disease is SCN5A, a gene encodes for alpha subunit of the cardiac sodium channel. The objective of this study is to explore SCN5A gene mutations in Chinese patients with Brugada syndrome.

METHODSFour patients diagnosed as Brugada syndrome and nine patients with suspected Brugada syndrome were chosen for the study. The exons in the functional regions of SCN5A gene were amplified with polymerase chain reaction and the amplified products were sequenced with Sanger method. If a mutation was identified, patient's family members were also screened.

RESULTSTwo heterozygous mutations were found in one family diagnosed as Brugada syndrome. One missense mutation was a G-->A transition in the first nucleotide of codon 95 in SCN5A gene exon 3, which was predicted to result in substitution of Valine with Isoleucine (V95I). The other missense mutation was a C-->T transition in the second nucleotide of codon 1649 in SCN5A gene exon 28, which was predicted to result in substitution of Alanine with Valine (A1649V). A heterozygous mutation was identified in one family suspected to have the disease. The mutation was a three nucleotides (TCT) deletion that caused Phenylalanine deletion in codon 1617 in SCN5A gene exon 28. The three mutations were not detected in 100 control chromosomes.

CONCLUSIONSMutation in SCN5A gene is one of the causes of Brugada syndrome in Chinese. Three novel SCN5A gene mutations were identified in Chinese with Brugada syndrome, which expands the spectrum of SCN5A mutations associated with the disease.

Adolescent ; Adult ; Aged ; Brugada Syndrome ; genetics ; Case-Control Studies ; Exons ; genetics ; Humans ; Male ; Middle Aged ; Muscle Proteins ; genetics ; Mutation ; NAV1.5 Voltage-Gated Sodium Channel ; Sodium Channels ; genetics

OBJECTIVETo evaluate the mechanism of increased invasion and migration of hepatocellular carcinoma (HCC) cells induced by vascular endothelial growth factor receptor-1 (VEGFR-1) activation.

METHODSVascular endothelial growth factor-B (VEGF-B) was used to induce and stimulate hepatocellular carcinoma cell line MHCC97-H. Morphologic changes of MHCC97-H were investigated. The expression of E-cadherin and alpha-catenin (two epithelial markers) and Vimentin and N-cadherin (two mesenchymal markers) was detected by reverse transcriptase polymerase chain reaction (RT- PCR), western blotting, and immunofluorescence staining. Cell invasion and migration test was performed.

RESULTSTreatment of MHCC97-H cells with VEGF-B led to morphologic changes characteristic of epithelial to mesenchymal transition (EMT), including loss of polarity, increased intercellular separation, and the presence of pseudopodia. Expression of the epithelial adhesion molecules, including E-cadherin and alpha-catenin, was decreased after VEGF-B treatment. Conversely, an increase in the expression of the mesenchymal cell markers, including N-cadherin and vimentin, was observed after VEGF-B treatment (P less than 0.05). VEGF-B-treated cells exhibited a change in E-cadherin from an organized, membrane-bound structure to a disorganized state in which it was noted to be dispersed throughout the cytoplasm. Pretreatment with VEGFR-1 blocking antibody 18F1 inhibited the change in localization of E-cadherin induced by VEGF-B treatment. The ability of invasion and migration of MHCC97-H was enhanced by VEGF-B reatment (P less alpha 0.05).

CONCLUSIONIncreased invasion and migration of HCC cells induced by VEGFR-1 activation was mediated by epithelial to mesenchymal transition.

Carcinoma, Hepatocellular ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo analyze the impact of efforts of community-based organizations (CBO) in HIV testing mobilization and case finding among men who have sex with men(MSM).

METHODSResults of HIV testing mobilization among MSM through CBOs in 15 program areas were collected and compared with corresponding HIV case reporting data to demonstrate the contribution of CBO-based HIV testing in HIV case finding among MSM from July 2008 to December 2011. Meanwhile,the proportion of screened HIV positives who received testing results notification,confirmatory test, following up and CD4 cell tests were analyzed and compared with those identified in medical institutions.

RESULTSA total of 196 075 HIV tests were performed for MSM, as a result of mobilization efforts of CBOs. Cumulatively 7704 new HIV cases were identified, accounting for 51.7% (7704/14 914) of all newly diagnosed HIV cases infected via homosexual sex in the program areas.Among the newly diagnosed MSM HIV infections in the program areas,the proportion of infections detected through the mobilization of CBOs increased from 35.4% (609/1722) in 2008 to 63.7% (2371/3722) in 2010, and 58.3% (3024/5189) in 2011. Compared with those identified through medical institutions, newly diagnosed MSM infections detected though CBOs testing mobilization have higher rates of receiving screening testing results notification (97.3% (4441/4563) vs 92.8% (13 140/14 153)) , (84.6% (2559/3024) vs 79.8% (5589/7002)) and CD4 cell tests (66.1% (1999/3024) vs 52.9% (3705/7002)), and a lower rate of receiving confirmatory test (78.6% (3588/4563) vs 85.6% (12 115/14 153)).

CONCLUSIONCBOs can take their advantages in mobilizing MSM to receive HIV test, and MSM HIV cases detected through CBOs have become the main source of MSM HIV case finding in program areas.

Community Health Services ; HIV Infections ; prevention & control ; HIV Seropositivity ; Health Promotion ; Homosexuality, Male ; Humans ; Male ; Mass Screening

OBJECTIVETo study the transmission route and epidemiological features of Clonorchis sinensis infection in Shenzhen area--the biggest immigration city of Southern China.

METHODSIn this study, we examined 1473 individuals (710 males and 763 females) to determine the current status of C. sinensis infection among the people in one village in Zhujiang river region, Guangdong province, China. Blood samples were detected on antibody of C. sinensis with enzyme linked immunosorbent assay,and stool specimens from sera positive cases were examined by modified Kato-Katz thick smear to confirm the density of infection. People were interviewed on their life styles under the structured questionnaire which was administered by trained staff members. Major content of the questionnaire included eating raw fish, using the same utensils for both raw fish and cooked food, using feces of domestic animals and human feces to feed fish and so on.

RESULTSAmong 1473 people examined, 70 (4.75%) were found infected with C. sinensis. By counting eggs per gram feces (EPG), it was found that heavy intensities of infection in males was stronger than that of females,and the overall average EPG was 41.87. Of 1473 interviewees, 54% of them did not know about fluke disease or its transmission route, 12% of those who knew about the fluke but believed that the infection caused no harm or only slight harm to their health. 27% of the interviewees ate raw fish at least 1-2 times per months with 5% of the families using the same utensils for both raw fish and cooked food. 40% of the fish ponds owners fed their fish with the feces of domestic animals and human feces.

CONCLUSIONTogether with these results, unhealthy behaviors, poor knowledge, inappropriate farming/fishery practices, eating raw fish were important factors influencing the C. sinensis prevalence in humans.

Adolescent ; Adult ; Animals ; Child ; China ; epidemiology ; Clonorchiasis ; epidemiology ; parasitology ; transmission ; Clonorchis sinensis ; pathogenicity ; Feces ; parasitology ; Female ; Humans ; Male ; Middle Aged ; Parasite Egg Count ; Reverse Transcriptase Polymerase Chain Reaction ; Sex Factors ; Surveys and Questionnaires ; Young Adult