Serious market failure, as a result of insufficient incentive, exists in the orphan drugs market. Through legislation, the United States designed and established its owns systematic and linked orphan drugs incentive mechanism, which direct sat research, definition, clinical trials and approval of orphan drugs, so as to change the supply and demand status of orphan drugs. Such incentive mechanism erables the United States possess the most ap-proved orphan drugs in the world, and effectively relieves the problem of market failure of the orphan drugs. The ex-perience of the United States provides beneficial reference for the establishment and positive development of orphan drugs incentive mechanism in China.

Objective To analyze the clinical effectiveness of using marginal donor kidney in living kidney transplant. Methods From November 2005 to June 2011,274 cases of living kidney transplant were performed in the First Affiliated Hospital of Zhengzhou University.The cases were divided into the marginal donors group ( Donor ages over 60 years old,suboptimal renal anatomy or physiology) of 66 cases and standard donors group of 208 cases.The clinical data were retrospectively analyzed.The criteria of marginal donors were as follows:36 cases of donors with age over 60 yrs (6 cases with renal cysts and 1 case with renal calculus),22 cases of renal cysts ( with diameter range from 4 mm to 40 mm ),4 cases of renal calculus (with diameter range from 3 mm to 6 mm),4 cases of low GFR (under 35 ml/min.The mean recipients' serum creatinine before surgery and after surgery on day 3,day 7,month 1,month 3,month 6,month 12,related complications,the rate of acute rejection and delayed graft function,1 year,3 year recipient/kidney survival were compared between the 2 groups,respectively. Results The serum creatinine levels in the marginal donor group and standard donor group were (242.7 ± 132.2 vs 185.6 ± 148.4) and ( 156.7 ±86.8 vs 122.2 ± 136.8 ) on day 3,day 7 respectively ( P ＜ 0.05 ).Nevertheless,there were no significant differences between the 2 groups in recipients' serum creatinines before surgery and after surgery on month 1,month 3,month 6,month 12,peri-operative complications,the rate of acute rejection and delayed graft function,1 year,3 year recipient/kidney survival (P ＞ 0.05). Conclusions Healthy old donors and donors with renal cyst (the diameter of renal cysts under 40mm) should not be the barriers to organ donation.To those living donors with low GFR,we should consider of donor age,donor/recipient body weight,donor/recipient body surface area and whether we could deal with the problem by surgical operation.Donor with renal calculus should be carefully evaluated.

Objective To study the local irritation of repeated intrathecal injection of Ziconotide Acetate,and to provide reference for irritancy evaluation ofintrathecal injection.Methods Sixteen New Zealand rabbits were assigned into two groupsat random:Control group and Ziconotide Acetate group,eight animals each group.Totally 50 μL saline or Ziconotide Acetate (100 μg/mL) were administrated by repeated lumbar intrathecal injection once daily for 7 d.Animal behavior was observed every day,and four animals in each group were sacrificed 2 d later after the last injection,the lumbar spinal cord was removed for histopathological examination and irritancy evaluation.The remaining animals were sacrificed for initancy evaluation 14 d later after the last injection.Results Only one animal died after anesthesia on day three in saline group,while no obvious adverse reactions were observed in other rabbits during the entire study,and no intrathecal irritant reactions of histopathological examination were found in both groups.The reversible minor mechanical damage was observed at the injection point,2 d after the last administration.Conclusion For 7 d repeated lumbar intrathecal injection in rabbits,no intrathecal irritant reactions observed in Ziconotide group,and the New Zealand rabbit could be used as a local irritation evaluation model.

BACKGROUND: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. METHODS: This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables. RESULTS: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups. CONCLUSION: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance. TRIAL REGISTRATION ClinicalTrials.gov, ChiCTR 1900023646.
Humans ; Bismuth/therapeutic use* ; Metronidazole/therapeutic use* ; Esomeprazole/pharmacology* ; Minocycline/pharmacology* ; Helicobacter pylori ; Potassium Citrate/therapeutic use* ; Anti-Bacterial Agents ; Tetracycline/adverse effects* ; Helicobacter Infections/drug therapy* ; Drug Therapy, Combination ; Amoxicillin

ObjectiveTo study the effect of upper limb robot-assisted therapy on upper limb function and cerebral cortex activation in stroke patients using functional near-infrared spectroscopy (fNIRS). MethodsFrom January, 2022 to January, 2023, 32 stroke patients in Zhejiang Rehabilitation Medical Center were randomly divided into control group (n = 16) and experimental group (n = 16). Both groups received routine neurological medication and routine rehabilitation. The control group received routine upper limb exercises, the experimental group received upper limb robot-assisted therapy. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and fNIRS (oxyhemoglobin, deoxyhemoglobin, and total hemoglobin) before and four weeks after treatment. NIRS_SPM was used for activation analysis, Homer2 was used for blood oxygen concentration analysis. ResultsAfter treatment, the score of FMA-UE increased in both groups (|t| > 5.910, P < 0.001), and was higher in the experimental group than in the control group (t = -2.348, P < 0.05). fNIRS activation results showed that, the activation increased in the experimental group after treatment in channel 17 (F = 9.354, P < 0.01), and it was more than that in the control group (F = 5.217, P < 0.05). fNIRS blood oxygen concentration results showed that, the blood oxygen concentration increased in the experimental group after treatment in channel 17 (F = 12.179, P < 0.01), and it was more than that in the control group (F = 4.883, P < 0.05). ConclusionThe upper limb robot-assisted therapy can improve the upper limb motor function and cerebral cortex activation of stroke patients.

¹⁷⁷Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of ¹⁷⁷Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.