With the in-depth study of related substances and the development of consistency evaluation of generic drugs, relative correction factors are gaining increasing attention. By analyzing the domestic and foreign literature on correction factors in recent years, this paper describes the correction factor component, the current measurement method and its application. The rules and key points of use of an impurity correction factor and its determination and application are described, and some problems in its determination and application are discussed, providing a reference and basis for the standardization of research on impurity correction factors in the future.

Objective To investigate the long-term oncological outcomes of laparoscopic radical hysterectomy (LRH) plus lymph node dissection (LND) and abdominal radical hysterectomy (ARH) plus LND for patients with stage Ⅰ a2-Ⅱ a2 cervical cancer.Methods A retrospective review of stage Ⅰ a2-Ⅱ a2 cervical cancer patients who underwent LRH + LND (n=372) and ARH + LND (n=434) at the First Affiliated Hospital of Sun Yat-sen University from Jan.2005 to Aug.2013 was performed.Individual patient matching was performed by the risk factors for recurrence [tumor size,lymph vascular space invasion (LVSI),depth of cervical stromal invasion,lymph node metastasis,parametrialinvolvement,and resection margin involvement] between two groups.After matched,a total of 203 patient pairs (LRH-ARH) were enrolled.The survival data,surgery data,intraoperative and postoperative complications were compared between the two groups.To assess the prognosis factors,the univariate and multivariate Cox's proportional hazards modelanalysis were conducted.Stratified analysis was performed based on the independent prognosis factors to investigate the survival data between the two surgery groups.Results (1) Surgery data:The operating time [(239±44) vs (270±42) minutes],estimated blood loss [(210± 129) vs (428±320) ml],the duration of bowel motility return [(2.0±0.8) vs (3.0± 1.6) days] and hospital stay [(11 ±6) vs (13±6) days] in the LRH group were significantly shorter than those in ARH group (all P＜0.01).(2) Intraoperative and postoperative complications:The intraoperative complications rate was similar betweentwo groups [6.4％(13/203) vs 6.9％(14/203),P=1.000].The rate of postoperative complications (excluded bladder dysfunction) in the LRH group were significantly lower than those in the ARH group [9.4％ (19/203) vs 20.2％ (41/203),P=0.002].While there was no significant difference in the rates of bladder dysfunction between two groups [36.5％ (74/203) vs 37.4％ (76/203),P=0.910].(3) Recurrence and survival data:There was no significant difference in the recurrence rates between the LRH group and ARH groups [7.9％ (16/203) vs 9.4％ (19/203),P=0.850].There were similar 5-year recurrence-free survival (RFS;92.1％ vs 91.1％,P=0.790) and 5-year overall survival (OS;93.7％ vs 96.1％,P=0.900).(4) Prognosis factor:In univariate analysis,the results showed that tumor size,International Federation of Gynecology and Obstetrics (FIGO) stage,adjuvant therapy,LVSI,stromal invasion,parametrium invasion,pelvic lymph node metastasis,and para-aortic lymph node metastasis were significantly associated with poor prognosis (all P＜0.01).However,age,body mass index (BMI),surgery type,histological type,grade were not significantly associated with poor prognosis (all P＞0.05).The multivariate analysis results,showed that tumor size,pelvic lymph node metastasis,and para-aortic lymph node metastasis were significantly associated with poor prognosis (all P＜0.01).Stratified analysis showed that,even in patients with tumor size ＞4 cm,pelvic lymph node metastasis positive,and para-aortic lymph node metastasis positive in all subgroups,there were not significant difference for the estimated 5-year RFS and 5-year OS between LRH and ARH group (all P＞0.05).Conclusion For patients with stage Ⅰ a2-Ⅱ a2 cervical cancer,LRH plus lymph node dissection is an oncologically safe and surgical feasible alternative to ARH.

Research on polymer impurities has always been important in the quality control of cephalosporins. Research on polymers in cephalosporins that lack active amino groups on the C-7 side chain has not been reported. Therefore, our study used cefazolin sodium, which is widely used in the clinic, as an example. The polymer in cefazolin sodium and its product "cefazolin sodium pentahydrate for injection" was analyzed by column switching liquid chromatography-high resolution mass spectrometry. Two polymer impurity peaks were detected and the possible structures of these polymers were suggested. Through two-dimensional liquid chromatography, the chromatographic peaks following Sephadex gel chromatography and high-performance gel chromatography were compared to those obtained by reverse high-performance liquid chromatography (HPLC) for cefazolin sodium as reported in the Chinese Pharmacopoeia. The HPLC method proves more suitable for polymer detection than Sephadex gel chromatography and high-performance gel chromatography. The method of polymer detection for cefazolin sodium was established using the method of related substances HPLC as described in the Chinese Pharmacopoeia.

The quality of some earlier developed antibiotics is usually ensured by the combination of HPLC purity and microbiological potency measurement in the pharmacopoeias of various countries because the relationship between their purity and potency is not clearly quantified. Due to potency is assessed using certain units of measurement, it can not be directly traced to the international system of units (SI unit). This has become a hotspot in the study of the quantitative relationship between purity and potency of antibiotics. It would be quite an achievement to simultaneously determine both purity and potency using HPLC methods during quality control. This study evaluated a multicomponent antibiotic product, gentamycin, as a test sample. First, pure samples of the C components of gentamycin: C1a, C2, C2a and C1 were prepared, separately. Second, quantitative relationship (theoretical potency) between the purity and potency of each C component of gentamycin were determined using 1H NMR, HPLC-ELSD and microbiological assay method. One milligram of gentamycin C1a, C2, C2a and C1 was equal to 1 286.98, 1 095.74, 1 079.52 and 739.61 gentamycin units, respectively. Finally, a method for the determination of gentamycin potency was established based on the proportion and content of C components of gentamycin. The unification of purity and potency for gentamycin was achieved using only HPLC-ELSD. It is also demonstrated that C components of gentamycin and micronomicin produce the same responses under ELSD, which means that it is not necessary to prepare separate reference standards for each C component of gentamycin and that quantitative testing can be performed accurately using only one micronomicin reference standard. This study simplified the previous method for the determination of the content of C components of gentamycin using HPLC-ELSD. The developed method is suitable for regular use as a part of quality control and can simplify the rigmarole quality control procedures provided in current pharmacopeias.
Chromatography, High Pressure Liquid ; Gentamicins ; chemistry ; pharmacology ; Magnetic Resonance Spectroscopy ; Microbial Sensitivity Tests ; methods ; Molecular Structure ; Quality Control ; Reference Standards

Objective To explore the role of tissue inhibitor of metalloproteinase-1(TIMP-1) during renal senescence by using human TIMP-1 transgenic mice.Methods Renal histological changes of wild type mice and transgenic mice at the age of 3,12,24 months were observed by periodic acid-schiff(PAS)staining of paraffin sections.The numbers of F4/80 positive cells were detected by immunofluoreseence.The protein expressions of TIMP-1,TIMP-2,matrix metalloproteinase(MMP)-9,MMP-2,intercellular adhesion molecule-1(ICAM-1),transforming growth factor?1(TGF-?1),collagenⅢand collagenⅣwere detected by Western blot.The activities of gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography respectively.Results Focal renal fibrosis was found in two genotypes with aging.At the age of 24 months,compared with wild type,in kidneys of transgenic type,the expressions and activities of gelatinases were dowregulated (MMP-2:2.08?0.20 vs.3.39?0.43;MMP-9:4.02?0.82 vs.6.72?1.40,all P＜0.05);the expressions of collagenⅢ,collagenⅣ,ICAM-1,and TGF-?1 were upragulated(0.72+0.11 vs.0.57?0.09;0.84?0.13 vs.0.6?0.11,0.72?0.12 vs.0.53?0.07; 0.69?0.12 vs.0.45?0.09,all P＜0.05),and the numbers of F4/80 positive cells were increased (18.8?4.4 vs.12.7?3.6,P＜0.05)with the upregulated expression and activity of TIMP-1(1.10?0.18 vs.0.62?0.09;50.75?7.25 vs.20.64?3.50,P＜0.05).Conclusions TIMP-1 could promote age-related renal fibrosis through enhancing inflammation reaction by ICAM-1 upregulation.

Objective To explore the effect of histamine on neurons in the hippocampal C1 area of SD rats and the behavior of depressive SD rats. Methods The effect of histamine on the discharge frequency of neurons in hippocampal C1 area was observed by in vitro extracellular recording of brain slices. The effect of endogenous histamine released to hippocampal neurons was observed through in vivo extracellular recording after the hypothalamus was electrically stimulated. In addition, the changes of motor activity and the ability of spatial memory of the rats with depression after microinjection of histamine into the hippocampal C1 area were observed by open-field test and Morris water maze test. Results The results of in vitro extracellular recording of brain slices showed that the hippocampal neurons were excited by histamine via H1 receptors rather than H receptors in a concentration dependent manner. The results of in vivo extracellular recording showed that endogenous histamine had a bidirectional effect, which means a short-term excitatory effect followed by a long-term inhibitory effect on the hippocampal neurons. After injected with histamine in the hippocampal C1 area,

A multicenter blinded randomized controlled trial (RCT) was conducted in accordance with international clinical trial standards to evaluate the efficacy and safety of Xuebijing injection in the treatment of severe community-acquired pneumonia (SCAP) under strict quality control condition. This article aims to illustrate key contents of the design ideas and implementation process of the RCT of Xuebijing injection in the treatment of SCAP, including the selection of research objects, design, implementation, and insights, etc., share experience with researchers of the respiratory and critical care, and provide reference for future studies in critical care.

OBJECTIVETo compare and evaluate the cost and effectiveness of endoscopic variceal ligation (EVL) at emergency plus octreotide versus octreotide alone in the treatment of acute esophageal variceal bleeding in cirrhotic patients.

METHODSSeventy-eight patients with active variceal bleeding under emergency endoscope, were assigned to two groups receiving either combined therapy of EVL at emergency and octreotide ('EVL' group) or a continuous infusion of octreotide alone ('octreotide' group). Both efficacy and cost-effectiveness were observed.

RESULTSThere were no significant differences between the two groups in patients' characteristics, supporting treatment or general treatment. In group EVL, there appeared a significantly higher rate in controlling bleeding and lower complication rate than that of octreotide group(94.4% vs.78.6%, P = 0.045 and 19.4% vs. 42.9%, P = 0.027, respectively). Early rebleeding and mortality rate were also lower in group EVL, but with no significant differences between them (2.9% vs. 7.7%, P = 0.358 and 5.6% vs. 14.3%, P = 0.205, respectively). The combined therapy had a significantly shorter time of hemostasis, less administration of octreoid, fewer units of blood transfusion and shorter hospital stay (P < 0.001). The median costs of the combined therapy and octreotide alone were RMB 9046.5 Yuan and 13 743.6 Yuan,respectively (P = 0.045). The cost-effective ratio of group EVL seemed superior to that of octreoid group.

CONCLUSIONThe therapeutic scheme of emergency EVL plus octreotide was a more cost-effective one for controlling acute esophageal variceal bleeding.

Combined Modality Therapy ; Cost-Benefit Analysis ; Emergency Medical Services ; Endoscopy, Gastrointestinal ; Esophageal and Gastric Varices ; complications ; Gastrointestinal Hemorrhage ; etiology ; therapy ; Humans ; Ligation ; economics ; Liver Cirrhosis ; complications ; Octreotide ; economics ; therapeutic use ; Treatment Outcome

Hepacivirus ; Hepatitis C ; therapy ; Humans

OBJECTIVETo study the effects of four kinds of traditional Chinese herbal compound, Sini powder, Banxiahoupu soup, Ganmaidazao soup and Guizhigancaolonggumuli soup, on the experimental acute stress behaviors and the hypothalamus-pituitary-adrenal gland axis.

METHODRats were divide into 7 groups: normal group, model 1 and 2 groups, Sini powder group, Banxiahoupu soup group, Ganmaidazao soup group, and Guizhigancaolonggumuli soup group. The behaviors of the rats and their CRH of the hypothalamus, ACTH of plasma and CORT of serum (by the means of radio-immunity) were detected.

RESULTSini powder could reduce the crossing times of open-field test( P < 0.01) and the contents of CRH and CORT (P < 0.01, P < 0.05); Banxiahoupu soup could extent the still time of tail-hanging test ( P < 0.05) and the content of CRH (P < 0.05); Ganmaidazao soup could prolong the still time (P < 0.05) and reduce the struggle times (P < 0.01) of tail-hanging test and reduce the contents of CRH, ACTH and CORT (P < 0.01, P < 0.05); Guizhigancaolonggumuli soup could reduce the crossing times of open-field test (P < 0.01) , extent the still time (P < 0.05) and reduce the struggle times ( P < 0.01) of tail-hanging test of tail-hanging test, also reduce the contents of CRH, ACTH and CORT (P < 0.01, P < 0.05).

CONCLUSIONThe four kinds of traditional Chinese herbal compound can increase the ability of anti stress by affect the different taches of the hypothalamus-pituitary-adrenal gland axle and change the stress behaviors, which are based on their respective functions of regulating Qi, dispersing phlegm, tonifying Qi and warming Yang.

Adrenocorticotropic Hormone ; blood ; Animals ; Behavior, Animal ; drug effects ; Corticosterone ; blood ; Corticotropin-Releasing Hormone ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Hypothalamo-Hypophyseal System ; drug effects ; Hypothalamus ; metabolism ; Male ; Materia Medica ; isolation & purification ; pharmacology ; Medicine, Chinese Traditional ; Ostreidae ; chemistry ; Plants, Medicinal ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; physiopathology