OBJECTIVE: To figure out the balance mechanism between brand-name drugs and generic drugs in American drug review. METHODS: This paper reviewed FDA laws and regulations, domestic and foreign literature to retrospect the basis of generic development and explore the brand-name drug companies' action to prevent generic competition. RESULTS AND CONCLUSION: The abbreviate new drug application, patent challenge and market exclusivity in the Hatch-Waxman Act were the basis of generic development. Brand-name drug companies prevented competition by occupying the market, refusing to provide samples, submitting citizen petitions to extend generic drug review time and extending the patent term and market exclusivity of brand-name drugs. The United States legislated and amended relevant laws and regulations, adjusted the generic drug user fee to maintain the stability of the balance, which is worthy of further research.

Objective: To assess fluid-attenuated inversion recovery (FLAIR) vascular hyper-intensity (FVH) and explore its relationship with CT perfusion (CTP) penumbral/infarct core mismatch ratio and diffusion weighted imaging (DWI) final infarct volume in acute ischemic stroke (AIS) patients with middle cerebral artery occlusion (MCAO). Methods: The CTP and MRI images of 38 AIS patients with MCAO were reviewed. The FVH score (longitudinal direction) [FVH score (L)] and FVH score (transverse direction) [FVH score (T)] were quantified on the FLAIR images. The FVH score (L) (range, 0-16) was based on a rostrocaudal extension of FVH and the FVH score (T) (range, 0-3) was based on FVH supply of the occluded MCA territory. The mismatch ratio was calculated from the ratio of the [mean transit time - cerebral blood volume (CBV)] lesion/CBV lesion on the CTP images. The DWI infarct volume was measured on the DWI images. Results: The mismatch ratio was larger for the group of FVH score (L)=7~8 than those of FVH score (L)=5~6 and FVH score (L)=3~4 (p=0.03), whereas the DWI infarct volume was smaller (p=0.04). Similarly, the mismatch ratio of FVH score (T)=2~3 group was larger than FVH score (T)=1 group (p=0.01), whereas the DWI infarct volume was smaller (p=0.02). Both FVH score (L) and FVH score (T) correlated positively with mismatch ratio (P=0.02, P=0.001, respectively), but negatively with DWI infarct volume (P=0.03, P=0.004, respectively). Conclusions: Higher FVH score is associated with larger mismatch ratio and smaller DWI infarct volume in AIS patients with MCAO. FLAIR vascular hyperintensity may represent collateral arterial circulation, and may play a role in protecting the ischemic penumbra.
Infarction, Middle Cerebral Artery

Background: Approximately 15–20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric?onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult?onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database. Methods: We made a prospective study of 225 cSLE patients (aged <16 years) and 1759 patients aged 16–50 years based on CSTAR registry. We analyzed initial symptoms, clinical presentations, SLE disease activity, damages, and outcomes of cSLE, as well as compared with aSLE patients. Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI ], 0.470–0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512–2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053–2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170–0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log?rank test (0.557, P = 0.455). Conclusions: cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5? year survival between cSLE and aSLE groups.

AIMTo develop high bioavailability preparations without irritation for Panax notoginsenosides.

METHODSThe effects of some additives such as microcrystalline cellulose, beta-cyclodextrin and hydroxypropyl cellulose on drug in the preparations were examined.

RESULTSSaponins of Panax notoginseng (PNS) was absorbed in rabbits more when administered intranasally than through other routines, and the formulations including MCC both gave high bioavailability and low irritation.

CONCLUSIONBioavailability of Panax notoginsenosides can be increased through changing routine of administration and formulations.

Administration, Intranasal ; Animals ; Biological Availability ; Bufo bufo ; Cellulose ; toxicity ; Cyclodextrins ; Drug Carriers ; Drug Delivery Systems ; Female ; Ginsenosides ; administration & dosage ; isolation & purification ; pharmacokinetics ; Male ; Nasal Mucosa ; metabolism ; Panax ; chemistry ; Permeability ; Rabbits ; Rats ; beta-Cyclodextrins

OBJECTIVETo compare lidocaine tincture and microemulsion for their transdermal permeation.

METHODSThe experimental model for percutaneous administration of lidocaine preparations in vitro was prepared using modified Franz diffusion cell.

RESULTSThe accumulated infiltration amount of lidocaine microemulsion in unit area was higher than that in its cream or tincture preparations.

CONCLUSIONThe transdermal permeation of lidocaine microemulsion in vitro can be more efficient than that of the tincture preparation, and the permeation is linearly dependent on the dose administered within a certain range.

Administration, Cutaneous ; Anesthetics, Local ; administration & dosage ; Drug Compounding ; Drug Delivery Systems ; Emulsions ; administration & dosage ; Lidocaine ; administration & dosage ; Skin Absorption

A terminal deoxynucleotidyl transferase ( TdT ) amplification based DNA-copper nanoclusters (CuNCs) sensor was developed for detection of L-histidine ( L-His). Single strand DNA containing poly-thymine ( T) sequences were synthesized by TdT in the presence of dTTP. In blank control, poly-T sequences worked as templates of CuNCs due to the affinity between thymine and copper ions( II) . Fluorescence intensity was enhanced when CuNCs formed with reducing agents. In the presence of L-His, the imidazolyl group of L-His worked as a chelating agent that formed L-His-Cu2+ chelated complex. Thus less copper ions were induced in poly-T sequences, and less CuNCs were obtained to produce week fluorescence signals. A good linear correlation was obtained between fluorescence change and the logarithm of the L-His concentration over the range of 5. 0 ×10-9-5. 0 ×10-4 mol/L. The detection limit was estimated as 3. 4 ×10-9 mol/L. And the recoveries were 97. 4%-104. 6% for the actual urine samples. Compared with other methods of synthetic CuNCs, this method allowed to specifically determining L-histidine without template or labeling, which showed good potential in biomedical and clinical analysis.

We conducted in-depth analysis on the use of a popular Chinese social networking and microblogging site, Sina Weibo, to monitor an avian influenza A(H7N9) outbreak in China and to assess the value of social networking sites in the surveillance of disease outbreaks that occur overseas. Two data sets were employed for our analysis: a line listing of confirmed cases obtained from conventional public health information channels and case information from Weibo posts. Our findings showed that the level of activity on Weibo corresponded with the number of new cases reported. In addition, the reporting of new cases on Weibo was significantly faster than those of conventional reporting sites and non-local news media. A qualitative review of the functions of Weibo also revealed that Weibo enabled timely monitoring of other outbreak-relevant information, provided access to additional crowd-sourced epidemiological information and was leveraged by the local government as an interactive platform for risk communication and monitoring public sentiment on the policy response. Our analysis demonstrated the potential for social networking sites to be used by public health agencies to enhance traditional communicable disease surveillance systems for the global surveillance of overseas public health threats. Social networking sites also can be used by governments for calibration of response policies and measures and for risk communication.

OBJECTIVETo observe the clinical efficacy and benefit response of extracorporeal high frequency thermotherapy (EHFT) combined with Chinese medicine (CM) in the treatment of patients with advanced nonsmall cell lung cancer.

METHODSThe study adopted a prospective, small sample and randomized controlled method, and the advanced non-small cell lung cancer patients were assigned to two groups according to the table of random digits, one having the treatment of EHFT combined with CM (the treatment group), the other only with CM (the control group). The patients in the treatment group were treated with EHFT one hour once per day, together with CM differentiation decoction, 250 mL orally taken, twice daily for 14 days as one cycle, and 3-4 cycles was performed. The patients in the control group were treated only with CM differentiation decoction using the same dose as the treatment group. The efficacies were evaluated after three to four cycles of treatment. Primary endpoints were disease control rate (DCR) and time to progression (TTP). Secondary endpoints were overall survival time and 1-year survival rate.

RESULTSSixty-six patients accomplished the study. After the patients underwent different treatments, none of the patients got a complete response or partial response in both groups. In the treatment group, DCR was 72.2%, and 10 had progression of disease (28.8%), while the DCR of the control group was 63.3%, and 11 had progression of disease (36.7%); there was a significant statistical difference (P <0.05), suggesting that the combined regimen had superiority on the DCR. As for long-term efficacy, the median survival time (MST) of the treatment group was 7.5 months, TTP was 5.5 months, and 1-year survival rate was 21.4 %; in the control group, the results were 6.8 months, 4.5 months and 16.6% respectively. There was significant statistical difference on TTP (P <0.05), but no difference on MST or 1-year survival rate.

CONCLUSIONEHFT combined with CM differentiation has better tolerance and short-term efficacy in the treatment of patients with advanced NSCLC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; therapy ; Combined Modality Therapy ; Disease Progression ; Female ; Humans ; Hyperthermia, Induced ; Lung Neoplasms ; therapy ; Male ; Medicine, Chinese Traditional ; Middle Aged

Phenolic compounds have multiple bioactivities, such as anti-oxidant, anti-tumor, anti-bacterial, and anti-inflammatory activities. Recent literatures have demonstrated that flavonoids have a significant anti-anxiety effect on the central nervous system. In addition, studies showed that flavonoids acted as pro-drugs, which were transformed into smaller phenols through intestinal microflora. The small phenolic metabolites were crucial for the anxiolytic effects of these flavonoids, indicating that natural small-molecule phenols(NSMP) generally have anxiolytic activities. In this paper, the supporting evidences (before June 2016) from SciFinder database have been summarized. Furthermore, NSMPs were classified according to chemical structures; their anxiolytic effects, mechanisms, and the structure-activity relationships were also discussed.

At present, METH has surpassed the traditional illegal psychoactive substances and become the most widely abused illegal psychostimulant in China.Endoplasmic reticulum ( ER) plays an important role in regulating the normal physiological functions of various cells by virtue of its strong membrane strnc- ture and a large number of enzymes on the membrane.Endoplasmic reticulum stress ( ERS) is a series of adaptive responses made by cells when ER homeostasis is destroyed.When ERS occurs, it will drive the activation of unfolded protein response (I PR ) , which aims to protect cells from stress, reduce biosyn- thetic load and help to rebuild cell homeostasis.Persistent ERS will further aggravate the pressure of ER and induce cell death by using UPR signaling pathway.'Hie neurotoxicity induced by METH is closely related to ERS.This paper elaborates on ERS and UPR signaling pathway, and summarizes the relationship between ERS.apoptosis and autophagy, so as to provide new ideas and potential therapeutic targets for the basic research and prevention of METH induced neurotoxicity mechanism.