ABSTRACT
Adolescent idiopathic scoliosis (AIS) is a common disease with the age of 10 to 18 years, the Cobb angle more than 10 ° on the coronal plane and combined with the rotation of the vertebral body without other organic lesions. The disease can lead to deformity, pain and even damage of cardiopulmonary function, which seriously affects the physical and mental health and quality of life of patients. For mild to moderate AIS patients, regular observation, braces and other conservative treatment methods can effectively delay the progress of scoliosis. For AIS patients whose conservative treatment is ineffective and reaches the surgical threshold, surgery is recommended. Currently, the prevalent surgical method is posterior vertebral body fusion represented by the pedicle screw internal fixation system, which can often achieve good clinical efficacy. In recent years, Physical Therapeutic Scoliosis Specific Exercise (PSSE) has become more and more popular because of its safety and effectiveness. At present, the specific indications for the treatment of AIS patients are gradually improving, the concept and technology of treatment are constantly updated, and the clinical efficacy is constantly improved. This article will start from two aspects of conservative treatment and surgical treatment, mainly describes the commonly used treatment methods in clinical progress and application as well as the problems faced, in order to provide a reference for the selection of clinical treatment.
ABSTRACT
Objective To analyze the evolution of rtI233V mutation in the reverse transcriptase domain of hepatitis B virus (HBV) and its association with adefovir dipivoxil (ADV) resistance. Methods The rate of detection of rtI233V mutation in 9830 patients with chronic HBV infection was analyzed. HBV reverse transcriptase genes isolated from serial serum samples of two patients were amplified by nested PCR, and clonal sequencing (>20 clones/sample) was performed to analyze the evolution of rtI233V mutations. The replica of pTriEx-HBV1.1 vectors harboring wild-type and mutant strains (rtI233V, rtN236T, rtI233V+rtN236T) were respectively constructed and transiently transfected into HepG2 cells. Media containing serial concentrations of lamivudine (LAM), ADV, entecavir (ETV), or tenofovir (TDF) were used to treat the cells. Then HBV DNA in the supernatants was quantitatively determined by real-time PCR in order to analyze HBV mutants' replication competence and phenotypic characteristics under the drug pressures. Results The detection rate of rtI233V mutation in 9830 nucleos(t)ide analogues-treated patients was 0.28% (28/9830), including 0.19% (19 patients) with rtI233V individual mutation and 0.09% (9 patients) with rtI233V mutation combining with rtN236T or other mutations. All of the patients had rtI233V had ADV exposure history: 16 (57.1%) of them received ADV monotherapy for over six months, and 12(42.9%) of them received ADV combined sequential therapy for over 12 months. Replication competence and phenotypic resistance analysis showed rtI233V and wild-type strains had similar viral replication competence, while rtN236T exhibited significantly lower replication competence compared with wild-type strains. rtI233V strains remained sensitive to LAM, ADV, ETV, and TDF and showed little influence on drug resistance when combined with rtN236T, but it showed ability to restore the defected replication capacity of rtN236T strains. Conclusions The rtI233V mutation is associated with sub-optimal response to ADV. Though it does not directly reduce virus sensitivity to ADV, rtI233V mutation enhances replication competence of ADV resistant strains, and it is a complementary mutation.