This paper identified misunderstandings of the measures taken in China to overcome the problems incurred by off-label uses (namely reliance on drug makers to modify their medicine specifications,on medical institutions to enhance their regulation and management of off-label uses,and on informed consent to avoid risks).Based on such findings,the paper named defects found with such measures,and puts forward feasible ideas and methods to make such off-label uses legitimate and reasonable.These include clarification of the legal status of the medicine specifications,encouraging authoritative guidance for off-label uses,and determining the subject of evaluation to approve the off-label uses as reasonable.Such efforts aim at helping off-label uses out of the legal difficulties.

Objective:To investigate the supply status of dementia care services in pension agency in Guang zhou,thus to put forward suggestions for improving the service quality of the long-term care for dementia.Methods:Using questionnaire research and individual interview,an interview survey was conducted among managers,dementia and nursing assistant in ten pension agencies in Guangzhou.The data was analyzed by SPSS16.0 statistical method.Results:The dementia had been increasingly paid attention by the pension agencies,but there were still considerable defects in the aspect of the zone set up and service supply;the professional quality of nursing personnel in pension agencies had steadily increased,but shorthanded situation was more obvious.Conclusions:It suggests that we should provide specialized nursing level and the classification standard of care requirements for dementia elders;strengthen the training of mental health worker to enhance the level of medical care and supply ability of nursing assistant;allocate the mental health resources rationally;explore the “combination of medical treatment and endowment” service model which meets the need of dementia elders.

Objective To observe the clinical efficacy of needle warming therapy plus pelvic floor muscle training in treating post-stroke neurogenic bladder.Method A total of 124 patients with post-stroke neurogenic bladder were divided into a treatment group and a control group by random number table, 62 cases in each group. The treatment group was intervened by acupuncture, moxibustion plus pelvic floor muscle training; the control group was intervened by Chinese patent drugs. The intervention was conducted with 2 weeks as a treatment course, for 3 treatment courses in total. The daily voiding frequency test and maximum cystometric capacity (MCC) in the two groups were measured before and after the intervention, and the clinical efficacies were compared between the two groups.Result Each item of the daily voiding frequency test in the two groups was significantly changed after the treatment (P<0.01). Each item of the daily voiding frequency test in the treatment group was significantly different from that in the control group after the treatment (P<0.01). The MCC was significantly changed after the intervention in both groups (P<0.01). The MCC in the treatment group was significantly different from that in the control group after the treatment (P<0.01). The recovery rate and total effective rate were respectively 35.5% and 96.8% in the treatment group versus 19.4% and 77.4% in the control group. There were significant differences in comparing the total effective rate (P<0.01) and the recovery rate between the two groups (P<0.05).Conclusion Needle warming therapy plus pelvic floor muscletraining can produce a significant therapeutic efficacy in treating post-stroke neurogenic bladder, and the therapeutic efficacy is obviously better than that of medication.

Objective To investigate the role of Ca2+/calmodulin-dependent protein kinase Ⅱ on pain behavior in a mouse model of bone cancer pain. Methods 40 male C3H/HeN mice were divided randomly into 5 groups:sham group (S group, n=8) ,control group (C group, n=8) and KN93 treat group (T1, n=8;T2, n=8;T3, n = 8 ). Group C and T were induced mouse models of bone cancer pain by intra-left-femur inoculations of osteolytic NCTC2472 cells while group S were injected only α-MEM. On the 14 d after inoculations,group S and C received intrathecal injection of 20% DMSO 5 μl . While group T1, T2, T3 received intrathecal injection of KN93 15nmol,30nmol,60nmol which dissolved in 5 μl 20% DMSO respectively. Mice received pain behavior tests including quantification of spontaneous flinches, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) before and at 0.5 h,2 h,4 h,8 h after administration. Results Treatment with KN93(15 nmol) have no effect on bone cancer pain,while treatment with KN93(30 nmol,60 nmol) can dose-dependently reverse quantification of spontaneous flinches, mechanical allodynia and thermal hyperalgesia which were induced by bone cancer pain, At 0. 5h after administration, the quantification of spontaneous flinches of the two groups ( (7.25 + 1.49 ), (4. 12 + 1.36 ) ) were decreased when compared with control group ( 11.62 + 1.92 ),PWMT((1.28 +0.14)g;(1.75 +0.46)g),PWTL((14.64 +2.12) s; (16.85 + 1.61)s)were increased when compared with control group ( (0.47 + 0. 16) g, ( 11.32 + 1.68 ) s) (P ＜ 0.05 ＝. The effect lasts for at least 4 h and disappears at 8 h. Conclusion CaMK Ⅱ may play an important role in the mechanism of bone cancer pain. Intrathecal KN93 injection can effectively attenuated bone cancer pain.

The unsatisfactory operation of the existing mechanism for resolving medical disputes by doctors and patients may be contributed to the instability of this mechanism, as lack of regulation constraints results in huge discrepancies of outcomes between identical cases. Specifically, the uncertainty for doctor-patient consultation in the guidelines, evaluation and decision mechanism,consultation process, and compensation calculation. In this consideration, it is recommended to elevate the mechanism stability of this consultation by means of uniform guidelines, third-party evaluation and decision, standardized consultation process, and unified compensation standard.

Objective:To optimize the formula of aprepitant nanocapsules. Methods: The central composite design–response surface methodology was used. The amounts of hydroxg propyl cellulose(HPC-SL) and sodium dodecyl sulfate(SDS) were set as the independent variables;the dissolution of aprepitant capsules at 15min and 30min, and the dissolution after accelerated at 40℃ and 75% RH for 6 months were set as the dependent variables. Quadratic polynomial mathematic models were used to evaluate the relation-ship between the independent and the dependent variables. According to the mathematic models,an effect graph was drawn. The opti-mized formula was chosen from the overlap of the contour graphs of the dependent variables. The similarity of in vitro dissolution curve was evaluated by using f2factor. Results:The correlation coefficient of quadratic polynomial mathematic model and the reliability was high. The measured values of the optimized formula were within the expected ranges. Conclusion: Aprepitant nanocapsules with the optimized formula by central composite design-response surface methodology meet the requirements. The results can provide evidence for the next industrial production.

Objective To learn the comments on the practice of "Management Regulations of Medical Institutions(Regulations below)" by those related to such Regulations. And to identify problems found in the application. Methods A questionnaire was designed by means of literature review and expert brainstorming, to learn the awareness of the respondents on the Regulations, and their comments on regional planning of medical institutions, setup approval authority, classification of medical institutions, and regulators of these institutions. A total of 1 000 questionnaires were delivered to medical institutions, health administrative authorities and patients at large 854 valid questionnaires were recovered, with the data analyzed in descriptive statistics. Results 90.7% of the respondents supported the revision of the main contents of the Regulations. 54.3% of them held that not all types of medical institutions need to be limited by regional planning; 69.1% of them held that the regulatory powers of different rankings on the business approval need to be revised; 56.9% of them held that the Regulations should clarify the legal status of other regulatory authorizes over medical institutions. The respondents also named 11 articles of the Regulations to be added. Conclusions A number of articles of the Regulations need to be revised, such as those on setup approval and classified administration, to meet administrative needs and medical institutions' development needs. In the meantime, interest relationship of health administrators, medical institutions and patients should be taken care of as well.

Objective To analyze the methods and effects for treating unstable posterior pelvic ring fracture combined with sacral nerve injury and further identify the relationships among the diagnostic methods,surgical approaches and clinical outcomes.Methods A total of 38 patients with posterior pelvic ring fracture combined with sacral plexus injury treated from January 2000 to January 2010 were enrolled in the study.There were 20 males and 18 females at an average age of 35 years (range,10 to 59 years).The causes of fractures included traffic injury in 20 patients,fall injury in 12,weighty object impingement injury in five,and stabbing injury in one.Classification of posterior pelvic ring fractures included fracture and dislocation of sacroiliac joints in eight patients,fracture of ilium wing in two and sacrum fracture in 28.According to the Denis typing of sacrum fractures,there was one patient with type Ⅰ fracture,14 with type Ⅱ fracture and 13 with type Ⅲ fracture.All 38 patients presented the decrease or loss of skin sensation around the lower extremities,perineal region and crissum.Simultaneously,30 patients suffered motor dysfunction of the lower extremities,while 20 patients had bladder and anus sphincter dysfunction or sexual disorder.Thirteen patients were suspected of sacral plexus avulsion and four of them were confirmed by myelography or MRI examination.All patients had at least one associated injury.The average ISS was 21.9 points ( range,9 to 47 points).Therapeutic methods were fracture reduction and fixation in the absence of nerve decompression for eight patients and nerve decompression for 30 patients including 26 patients being also managed by fracture reduction and fixation.Operation time ranged from 6 days to 6 months.The clinical outcomes were evaluated according to the British Medical Research Council (BMRC) evaluation criteria of sensation and movement function.Results Thirty-four patients were followed up for average 4.9 years ( range,1 to 10 years),during which their pelvis obtained stable recovery.The neurological outcome was excellent in two patients,good in four and unchanged in two in the nondecompression group and was excellent in 16 patients,good in nine and unchanged in one in the decompression group,with the decompression group superior to the non-decompression group ( P ＜ O.05 ).Conclusions For unstable posterior pelvic ring fracture combined with sacral nerve injury,nerve decompression and release combined with internal fixation can better improve the sacral nerve function and obtain good pelvic ring stability and is worth of clinical application.

The disability and mortality of acute ischemic stroke are very high,which brings great burden to family and society.Timely and effective vascular recanalization is possible to make a good prognosis for patients.Since 2008,the intravenous thrombolytic therapy for patients with acute ischemic stroke within the time window has become the recommended treatment scheme of the guidelines in different countries.However,intravenous thrombolysis has the disadvantages of low vascular recanalization rate,narrow treatment time window,and relatively more contraindications,which limits its clinical application.In recent years,with the appearance of stent-like thrombectomy devices,mechanical thrombectomy within the time window has gradually become the mainstream treatment scheme for acute ischemic stroke.The latest guidelines for stroke treatment recommend the use of intravenous thrombolytic bridging endovascular thrombectomy within the time window.However,it is still unclear whether intravenous thrombolysis will increase the rate of vascular recanalization,improve clinical outcome,and increase the risk of intracranial hemorrhage before thrombectomy.This article reviews the vascular recanalization rate,clinical outcome,and intracranial hemorrhage risk of bridging therapy and direct mechanical thrombectomy.

Objective:To compare the differences of reference intervals (RI) established by two types of indirect methods for 34 biochemical analytes, and to explore the possible factors that affect the consistency of the two methods.Methods:This was a retrospective study. Based on data of albumin (Alb), alkaline phosphatase (ALP), alanine aminotransferase (ALT), apolipoprotein A1(ApoA1), ApolipoproteinB (ApoB), aspartate aminotransferase (AST), calcium (Ca), cholinesterase (ChE), chloride (Cl), creatinine (Cr), high-sensitivity C-reactive protein (hsCRP), Cystatin (CysC), direct bilirubin (DBil), free fatty acid (FFA), glycated albumin(GA), gamma-glutamyltransferase (GGT), glucose (Glu), high density lipoprotein cholesterol (HDL-C), potassium (K), lactate dehydrogenase (LD), low density lipoprotein cholesterol (LDL-C), lipoprotein a [Lp (a)], sodium (Na), phosphorus (P), prealbumin (PA), superoxide dismutase (SOD), total bile acid (TBA), total bilirubin (TBil), total cholesterol (TC), total carbon dioxide (TCO 2), triglyceride (TG), total protein (TP), uric acid (UA) and urea (UR) of individuals who underwent physical examination at Peking Union Medical College Hospital from January 1, 2018 to December 31, 2019, Box-Cox algorithm was used to improve the data distribution and Tukey method was used to identify outliers. Variance component model was established, and standard deviation ratio (SDR) was calculated to determine whether the RIs of 34 biochemical analytes should be established according to age or sex The non-parametric method and kosmic algorithm were used to establish the RIs and 90% confidence intervals (CIs) of 34 biochemical analytes, and the coincidence of the 90% CIs of the reference limits for two methods was compared. Results:The skewness coefficients of ALP(male, female18-59), ALT, AST, hsCRP, DBil, GGT, Lp (a), TBA, TBil, TG, Glu, HDL-C(male) and CysC, GA, UR in the elderly group deviated from 0, and their kurtosis coefficients also deviated from 3. For these biochemical analytes, the point estimates of the RIs established by the two methods differed greatly and the 90% CIs did not overlap. The analytes with good normality were Alb, ApoA1, ApoB, Ca, ChE, Cl, Cr(E), CysC(18-59), FFA, GA(18-59), HDL-C(female), K, LDL-C, Na, P, PA, SOD, TC, TCO 2, TP and UR. The consistency is good. Except for Ca, 90% CIs of reference limits for some analyte between the two methods coincide with each other. Conclusions:The consistency of different indirect methods is affected by the normality of data.