Drug transporters are functional membrane proteins located in various tissues, which play vital roles in absorption, distribution and excretion of drugs, especially those located in intestine, liver and kidney. The expression and function of transporters will alter in diseases state, which affects the therapeutic effects of drugs by altering their pharmacokinetics. In this review, we focus on the alterations in related transporters and the effect on the drug therapy in common intestinal diseases, liver diseases, kidney diseases and diabetes mellitus.
Biological Transport ; Diabetes Mellitus ; pathology ; Humans ; Intestinal Diseases ; pathology ; Intestines ; Kidney ; Kidney Diseases ; pathology ; Liver ; Liver Diseases ; pathology ; Membrane Transport Proteins

Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.

Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities ; diagnosis ; Heart Defects, Congenital ; diagnosis ; Humans ; Intellectual Disability ; diagnosis

Objective To evaluate the effects of Achilles tendon lengthening on talipes equinus in children with spastic cerebral palsy. Methods From December, 2013 to June, 2014, seventeen spastic cerebral palsy children with talipes equinus (34 feet) received Achilles ten-don lengthening. Ankle dorsiflexion range of motion (ROM) and surface electromyography from tibialis anterior and medial head of gastroc-nemius were measured before and 8 to 12 months after operation, respectively. ROM of passive and active dorsiflexion, root mean square (RMS) of tibia muscle group and co-contraction ratio (CR) when standing were compared. Results The ROM of ankle passive and active dorsiflexion increased (Z>4.867, P<0.001), while the RMS of gastrocnemius muscle decreased when ankle passively dorsiflex (t=4.31, P<0.001). RMS of tibialis anterior and gastrocnemius muscle changed little when standing (Z<1.291, P>0.05), while CR reduced (t=2.38, P<0.05). Conclusion Achilles tendon lengthening can improve the coordination of tibia muscle group to increase the ROM of ankle for chil-dren with talipes equinus after spastic cerebral palsy.

Background Trans-scleral fixation of intraoculalen(IOL) hamade greaprogress,buthe long-term stability of the implanposition of IOL aftesurgery inoideal.Objective Thistudy wato investigate the relevanfactorof IOL dislocation aftetrans-scleral fixation of IOL.Methodrespective case-observational study wadesigned.The clinical datfrom 321 eyeof 321 patientwho had received trans-scleral fixation of IOL were collected.total of 263 patientcompleted the effeetive follow-up,and 164 patientwith the follow-up fomore than 5 years.No IOL dislocation occurred within 5 yearin all 263 eyes.The relationship between IOL material,IOL implantation location,the time of IOL dislocation and the intraoculapressure with IOL dislocation were analyzed.ResultIOL dislocation appeared 7-10 yearaftesurgery in 9 eyewith an incidence rate of 5.49％.Breakage of IOL suture wafound in all the eyewith IOL dislocation.Dislocation wamore frequently found in IOL performed in the oblique position than thain the horizontal position (10.0％ vs.3.5％).The rate of IOL dislocation wahighesin traumatiretinal detachmeneyes,apercentage of 33.33％.Single piece IOL wamore easily dislocated.ConclusionThe breakage of anchosuturein IOL ileading cause of IOL dislocation aftetrans-scleral fixation of intraoculalens,which may be associated with the weighresulting from the fixation procesin non-level angulaIOL.Iirecommended thaIOL should be fixed in the horizontal position.

Objective To explore clinical characteristics of diagnosis and treatment of solid-cystic papillary tumor(SCPT) of the pancreas in children.Methods There were retrospectively analyzed about the 7 patients treated in our hospital for SCPT,with the ave-rage age of 11.5 years.All patients complained abdominal pain following a trauma(71.4%) or overeating(28.6%).The main presentation was abdominal mass.Of the 7 patients,4 received distal pancreatectomy,2 pancreatico-duodenectomy,and 1 only biopsy.Results The nicks of all patients were primany hed.All patients were pathologically confirmed as SCPT after operation.All patients were followed up for 4 monthes to 4.5 years,the recent result was well.Conclusions SCPT is a low-grade malignant tumor,which is often asymptomatic,but the patients with symptoms generally suffer from an abdominal mass or abdominal pain.The prognosis is excellent after operation.

OBJECTIVETo compare therapeutic effects between surgical and conservative treatment for postoperative lumbar discitis.

METHODSFrom January 2004 to January 2009, 41 patients (17 males and 24 females ranging the age from 37 to 68 years with an average of 53.6 years) with postoperative lumbar discitis were retrospectively studied and divided into two groups. There were 19 patients in operation group, 22 patients in conservative group. Clinical data and features,image data, laboratory examinations, antibiotics utilization, hospital stays and sequelae were recorded and analyzed. Visual analogue scales system (VAS) and Oswestry disability index (ODI) were applied to evaluate therapeutic effects.

RESULTSAll patients were followed up over 2 years. Imaging revealed good bone fusion and no occurrence of discitis. VAS score and ODI at 1 month, 1 year and 2 years were significantly improved after treatment (P < 0.01). While VAS and ODI in operation group at 1 month were improved more than that of conservative group (P < 0.01), and there was no significant difference between two groups at 1 year and 2 years (P > 0.01).

CONCLUSIONSurgical and conservative treatment for postoperative lumbar discitis is effective. Surgical treatment is superior to conservative treatment in a short time, while conservative treatment can achieve long-term satisfactory curative effects.

Adult ; Aged ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Discitis ; drug therapy ; surgery ; Female ; Humans ; Lumbar Vertebrae ; drug effects ; surgery ; Male ; Middle Aged ; Postoperative Complications ; drug therapy ; surgery ; Retrospective Studies ; Treatment Outcome

Objective To assess the diagnostic yields of clinical chromosomal microarray ( CMA) testing for patients with neurodevelopmetal disorders ( NDD) , and to characterize the spectrum of pathogenic copy number variation(CNV) in NDD.Methods The study was a cross-sectional study.NDD patients from Shanghai Children′s Medical Center ( SCMC ) from April 2014 to April 2015 were recruited.DNA samples from SCMC cohort were tested on Affymetrix Cytoscan Dx microarray platform.The diagnostic yields of CMA testing were further assessed for the whole NDD cohort and each subgroup.Results A genome-wide genotype-phenotype analysis on a total of 107 NDD cases with CMA testing was conducted.Based on the SCMC clinical cohort, the overall diagnostic yield of CMA testing for NDD patients was 20.6%(22/107). Excluding one case with chromosomal aneuploid, the frequency of non-polymorphic CNVs of the rest NDD cases were 25.5%(27/106).The diagnostic yield for developmental delay/intellectual disorder(DD/ID) and autism spectrum disorder(ASD)were 26.3% (15/57) and 10.2%(4/39) respectively.DD/ID was more likely to be associated with CNV than ASD and attention-deficit/hyperactivity disorder(ADHD).Five recurrent genomic loci were significantly enriched in patients including 1q21.1-q21.2, 15q11.2-q13.1, 22q11.2, 7q11.23 and 17q11.2.Conclusion CNV is an important pathogenesis in NDD.

In order to test the equilibrium solubility of puerarin in different solvents and solubilizer,cilia toxicity and irritation of these excipient, the balance method, toad in the ciliary body toxicity and rat nasal mucosa irritation were used respectively. Results showed that puerarin solubility was 56.44 g x L(-1) in combined solvent of 30% PEG200 and 10% Kolliphor HS 15. With normal saline solution as negative control and sodium deoxycholate as positive control, the effects of 30% PEG200, 30% PEG 400, 10% Kolliphor HS 15 and combination of 30% of PEG200 and 10% Kolliphor HS 15 on toad palate cilium were observed and cilia movement duration was recorded. The results indicated that there was no significant difference in cilia movement duration among 30% PEG200, 10% Kolliphor HS 15 and normal saline group. The rats long-term nasal mucous membrane irritation of 30% PEG 400, 10% Kolliphor HS 15, which had no cilia toxicity, was studied, with normal saline solution as negative control. There were no significant difference revealed on rat nasal mucosa epithelial thickness among 30% PEG 400, 10% Kolliphor HS 15 and normal saline. Above researches showed 30% PEG 400, 10% Kolliphor HS 15 was ideal for solubility of puerarin nasal drops and showed a lower cilia toxicity and irritation, and can be used as the solvent and solubilizer of puerarin nasal drops.
Administration, Intranasal ; methods ; Animals ; Anura ; Cilia ; chemistry ; Female ; Isoflavones ; chemistry ; Male ; Nasal Mucosa ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Solubility ; Solvents ; chemistry