Objective To probe into the strategies for improving the accessibility to orphan drugs for patients of rare diseases in China. Methods Analysis of typical cases of orphan drug use in recent years in China, interviews of hospital administrators and clinical doctors, and analysis of the present health insurance policies in China for orphan drugs, definition of the concept of drug accessibility, clarification of the factors hindering orphan drug accessibility. Results Four factors are found to hinder orphan drug accessibility in such aspects of science and technology, supply, information transfer and medical assurance in China's medicine and healthcare system. These subjective and objective factors affect drug accessibility of the patients of rare diseases, denying them of drug accessibility, of drug use in time, and of affordability of such drugs. Conclusion To raise the orphan drug accessibility in China, it is necessary to define basic concepts and incentive mechanism of rare diseases and orphan drug, design and raise the response mechanism of the medicine and health system in orphan drug supply, build a three dimensional cooperation model between such parties as the government, enterprise and patient, and reduce patients' economic burdern.

The first metatarsophalangeal joint bending plays an important role in the foot movement. However, the existing researches mainly focused on the movement scope of the joint and the clinical treatments of related foot diseases. In order to investigate the effects of the first metatarsophalangeal joint bending on human walking gait stability, the present researchers recruited 6 healthy young men to perform the first metatarsophalangeal joint constraint (FMJC) and barefoot (BF) walking tests. Data of the temporal and spatial parameters, the joint angles of lower limbs, the ground reaction forces (GRF) and utilized coefficients of friction (UCOF) were collected and analyzed. The results showed that, since hip and knee could produce compensation motions, the FMJC had no significant effects on waking gait, but the slip and fall probability increased significantly.
Friction ; Gait ; Humans ; Male ; Metatarsophalangeal Joint ; physiology ; Walking

In order to explore new ways in restraining the ascending blood pressure, this paper reports a research on the effects of multi-mode audio frequency pulse modulating laser irradiation with electrical stimulation on the hemorrheology and blood pressure of the spontaneously hypertensive rats (SHR). Forty male SHR were randomly divided into four groups: Group A (control), Group B (treated with electrical stimulation on stomach 36 point (ST-36)), Group C (treated with low level pulse laser irradiation on Erjian acupuncture point), Group D (low level laser irradiation together with electrical stimulation on Erjian acupuncture point and ST-36). Laser irradiation lasted for 45 min/ day, while electrical stimulation lasted for 30 min/day. After 10 days' treatment, we compared the hemorrheology and blood pressure of the rats in the four groups. The results were that values of hemorrheology in group A and group C were obviously improved compared with those in the other two groups. Meanwhile, the blood pressures in the three treated groups (B, C, and D) were lower than in the control group after the treatment, and the value of the rats in group A was the lowest. In conclusion, the treatment the laser irradiation combined with electrodes stimulation on spontaneously hypertensive rats brought better results of hemorrheology and blood pressure in the tested rats.
Acupuncture Points ; Animals ; Blood Pressure ; physiology ; Blood Viscosity ; Electric Stimulation ; Electroacupuncture ; Hemorheology ; physiology ; Hypertension ; blood ; physiopathology ; therapy ; Laser Therapy ; Male ; Rats ; Rats, Inbred SHR

OBJECTIVETo evaluate the clinical efficacy of domestic sevoflurane by comparing the pharmacokinetic and pharmacodynamic characteristics of domestic sevoflurane and an imported product.

METHODSEighty patients undergoing general anesthesia for transabdominal hysterectomy were equally randomized into domestic sevoflurane group and imported sevoflurane group. The following data were recorded and compared: vital signs; change of sevoflurane concentrations in the induction period and recovery period; the time when inhaled sevoflurane concentration reached half of the pre-set concentration of the vaporizer; the time when the end-tidal sevoflurane concentration reached half of the pre-set concentration of the vaporizer; the time when the end-tidal sevoflurane concentration reached half of inhaled sevoflurane concentration; the time of the end-tidal sevoflurane concentration reached 0. 8 MAC in the induction period; the recovery time; the extubation time; and time to recovery of consciousness.

RESULTSThe general conditions of the two groups were not significantly different. The pharmacokinetic and pharmacodynamic parameters at the intra-operative time points as well as the minimal alveolar concentration, the inspired and end-tidal sevoflurane concentrations, and the time to recovery of consciousness also showed no significant differences between the two groups.

CONCLUSIONThe domestic sevoflurane has similar pharmacokinetic and pharmacodynamic characteristics as the imported products. It can serve as a cost-effective product for transabdominal hysterectomy.

Adolescent ; Adult ; Aged ; Anesthesia, Inhalation ; Anesthetics, Inhalation ; pharmacokinetics ; Double-Blind Method ; Female ; Humans ; Hysterectomy ; Methyl Ethers ; pharmacokinetics ; Middle Aged ; Young Adult

Objective:The effect of serum thyrotropin receptor antibody (TRAb) on permanent hypothyroidism (HT) after 131I treatment in Graves disease patients and its predictive value Methods:479 Graves' disease patients who underwent 131I treatment at the Nuclear Medicine Department of North China University of Technology Affiliated Hospital from October 2013 to October 2021 were selected. Among them, 350 cases (permanent HT group) had permanent HT during follow-up, while 129 cases (non permanent HT group) did not. Collect general clinical data such as gender, age, degree of thyroid enlargement, as well as indicators such as iodine intake rate, thyroid function, and treatment dose 24 hours before treatment, from two groups of patients. Compare the general clinical data and pre treatment levels of various detection indicators between two groups of patients, analyze the risk factors for permanent HT in Graves disease patients after 131I treatment, and evaluate the predictive value of pre treatment serum TRAb levels, and evaluate the consistency between the predicted results and clinical diagnosis. The econometric data with a normal distribution is represented by xˉ± s, and two independent sample t-tests are used for comparison between the two groups; The econometric data that do not conform to the normal distribution are represented by M（ Q1， Q3）, and the Wilcoxon rank sum test is used for comparison between the two groups; The counting data is represented as an example (%), and the comparison between the two groups is conducted using the four grid χ 2 test, while the comparison of grade data is conducted using the Willcoxon rank sum test; The logistic regression model was used for multivariate analysis. Draw a subject work characteristic curve to evaluate the predictive efficacy of TRAb, and screen the predictive threshold based on the Chayoden index; Calculate sensitivity and specificity, and evaluate the consistency between the predicted results and clinical diagnosis by calculating Kappa values. Results:There were no statistically significant differences in gender, age, degree of thyroid enlargement, 24-hour iodine uptake rate, serum thyroid stimulating hormone, free triiodothyronine, free thyroxine levels, and 131I treatment dose between the permanent HT group and the non permanent HT group (all P>0.05); The pre treatment TRAb levels in the permanent HT group were higher than those in the non permanent HT group [14.51(4.95,33.58) U/L vs 3.40(1.67,16.5) U/L], with a statistically significant difference ( Z=5.87, P<0.001). The results of multivariate logistic regression analysis showed that pre treatment TRAb levels were a risk factor for permanent HT in Graves' disease patients after 131I treatment (odds ratio=1.042,95% confidence interval: 1.025-1.059, P<0.001). The area under the working characteristic curve for predicting permanent HT in Graves' disease patients after 131I treatment with pre-treatment TRAb levels is 0.674 (95% confidence interval: 0.616~0.732), and the optimal critical value is 7.025 U/L. Using TRAb>7.025 U/L before treatment as the standard for predicting postoperative permanent HT in patients, the sensitivity and specificity were 73.7% and 75.2%, respectively. The predicted results showed moderate consistency with clinical diagnosis ( Kappa=0.426). Conclusions:The pre treatment TRAb level is a risk factor for permanent HT in Graves disease patients after 131I treatment ( P<0.001), and the diagnostic efficacy of permanent HT is best when TRAb>7.025 U/L.

OBJECTIVETo understand the etiology of hand, foot and mouth disease (HFMD) in Guangzhou area in 2008.

METHODTotally 1023 clinical specimens were collected from pediatric patients suspected of HFMD in 2008. TaqMan real-time RT-PCR were used for detection of enterovirus 71 (EV71), Coxsackievirus A16 (CA16) and other enteroviruses. The specimens which were enterovirus positive by RT-PCR method with universal primer but EV71 and CA16 negative, were amplified and sequenced for 5'untranslated region.

RESULTEnterovirus was identified from 434 of 1023 samples and detection rate of enterovirus was 42.42%; of the 434 samples, 276 were positive for EV71 (63.6%), 126 for CA16 (29%), 4 samples for enterovirus 84, 3 for Echovirus 11, 2 for Echovirus 9, 3 for Coxsackievirus B3, 4 for Coxsackievirus A10, 3 for Coxsackievirus A6, 6 for Coxsackievirus A12 or A5, and for 7 samples typing was difficult.

CONCLUSIONThe major causative agents of HFMD in Guangzhou were EV71 and CA16 in 2008, and EV84, CA10, CA12, CA6, COSB3, ECHV11, ECHV9 were also the pathogens for smaller proportions of patients.

Child ; Child, Preschool ; China ; epidemiology ; Coxsackievirus Infections ; epidemiology ; DNA Primers ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male ; RNA, Viral ; Reverse Transcriptase Polymerase Chain Reaction

Immunoassay is of great importance in the field of clinical detection. Our group proposes the inductively coupled plasma mass spectrometry ( ICP-MS) based immunoassay. Multiplex immunoassay can be realized by stable isotope tagging strategy combined with ICP-MS detection. Since then, large amount of researches in this field have been made at home and abroad, and the method has been proved applicable to the analysis of biological small molecules, proteins, nucleic acids and cells. In this article, the history and development of immunoassay, the characters of ICP-MS based immunoassay, single component and multiplex immunoassay, and the magnetic immunoassay that is recently fast developed are reviewed. The prospect of the developing tendency is also anticipated, hoping to provide references for the research in this field.

BACKGROUND/AIMS: A large number of studies have shown that function constipation (FC) has an extremely high incidence of mental and psychological disorders. Cranial electrotherapy stimulation (CES) was applied to the treatment of psychological disorders such as anxiety and depression. We explored the effects of CES combined with biofeedback therapy (BFT) on the psychological state, clinical symptoms, and anorectal function in patients with FC. METHODS: A total of 74 patients with FC were randomly divided into 2 groups. The control group received BFT. CES combined with BFT was carried out in the experiment group. All patients were assessed using the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Wexner constipation score at baseline and the end of each course. Anorectal manometry and balloon expulsion tests were performed before and after treatment. RESULTS: After treatment, the participants in the experiment group had significantly lower score SAS, SDS, and Wexner constipation scores than the control group (all P < 0.05). The number of successful expulsion in the experiment group was larger than the control group (P = 0.016). CONCLUSIONS: CES combined with BFT was effective in improving the psychological status of anxiety, depression, and bowel symptoms in patients with FC.
Anxiety ; Biofeedback, Psychology* ; Constipation* ; Depression ; Electric Stimulation Therapy* ; Humans ; Incidence ; Manometry ; Treatment Outcome

Aim To investigate the role and mecha-nism of exchange protein directly activated by cAMP (Epac) protein in the paraventricular nucleus(PVN) of the hypothalamus in the development of inflammatory pain in rats. Methods Adult SD male rats were cho-sen to establish the model of inflammatory pain through subcutaneous injection of complete Freund's adjuvant(CFA) on the center of left hind foot. Western blot was used to detect the changes of the expression of Ep-ac protein. Thermal withdrawal latency(TWL) was ob-served after the PVN injecting 8p-CPT-2′-O-Me-cAMP (8p-CPT),the agonist of Epac. Then activated down-stream MEK1/2 protein of Epac in PVN was detected using Western blot when the potency was the strongest.Results ① Compared with normal saline(control group),TWL decreased significantly on d 1, d 3, d 5, d 7,d 9 on the ipsilateral foot of CFA group rats(P<0.01),whereas it returned to normal level in d 13;the paw mechanical withdrawal threshold(PMWT) de-creased significantly on d 6,d 8,d 10,d 12 and d 14 (P<0.05);②Compared with the control,the Epac1 protein in CFA group rats began to decrease from d 3, and significantly decreased on d 3 and d 9(P<0.05), however the expression of Epac2 had no significant change, meanwhile p-MEK1/2 protein decreased sig-nificantly on d 3(P<0.05);③Compared with micro-injection of saline into the PVN(Saline group), the heat hyperalgesia of 20 min and 1h decreased signifi-cantly and TWL increased significantly after PVN ad-ministration of 8p-CPT(8p-CPT group)(P <0.05);paraventricular nucleus p-MEK1/2 protein expression increased significantly in 30 min(P <0.05) and re-covered to normal level 2 h after administration. Con-clusion The Epac1-MEK1/2 signaling pathway in the paraventricular nucleus of the hypothalamus may be in-volved in the development of chronic inflammatory pain induced by CFA.

OBJECTIVETo investigate the prevalence of Anaplasma phagocytophilum in small mammals from the forest area of Hengduan Mountains in southwestern China.

METHODSSmall mammals captured from Gaoligong and Xianggelila mountainous area of Yunnan province were detected by PCR amplification. The sequences of 16S rRNA and Msp4 gene fragments from positive samples were compared with corresponding sequences deposited in GenBank.

RESULTSA total number of 436 small animals, which belongs to 5 orders 18 genera 35 species were tested, 32 (7.34%) were positive in 6 genera 11 species. There were 8.64% (26/301) positive in 25 species at Goligong mountainous areas, and 4.44% (6/135) were positive in 19 species at the Xianggelila mountainous areas. Positive small mammals were most rodents. The nucleotide sequences of A.phagocytophilum 16S rRNA gene amplified from small mammals varied from 99% - 100% and were 99% - 100% similar with the corresponding segments of A. phagocytophilum from Jilin deposited in GeneBank. The sequences of A. phagocytophilum Msp4 gene showed that there was 95% - 97% similarity with the corresponding sequences registered in GenBank.

CONCLUSIONA. phagocytophilum was firstly identified in 6 genera 11 species small mammals from a forest area of Hengduan Mountainous areas in southwestern China. Rodents might serve as the primary hosts indicating the potential risk to the domestic animals and human beings in this area.

Anaplasma phagocytophilum ; classification ; genetics ; Animals ; Base Sequence ; China ; epidemiology ; DNA, Bacterial ; genetics ; Ehrlichiosis ; epidemiology ; veterinary ; Molecular Sequence Data ; RNA, Ribosomal, 16S ; genetics ; Rodentia ; microbiology ; Sequence Analysis, DNA