OBJECTIVE:To propose policy recommendations for China to solve medicines shortage fundamentally. METH-ODS:The causes of medicines shortage in China were analyzed. Chinese,American,Canadian and European literatures and the government website of typical countries about responses to medicines shortage since 2010 were searched and reviewed. RESULTS& CONCLUSIONS:Medicines shortage in China are due to regulation and policy changes and unfair competition. Both China and foreign countries face the problem of medicines shortage to some extent,either due to demand side or supply side. It is necessary to improve related laws and regulations to deal with medicines shortage,establish multi coordinative mechanism,shortage monitor-ing system and information and communication network platform with the patient-centered approach,leave reasonable profit for pharmaceutical production and distribution enterprises and crack down hoarding of raw materials. The experiences of typical coun-tries in defining clear responsibility for each stakeholder in the medicines supply chain,establishing comprehensive policies and co-ordinative mechanisms in response to medicines shortage are valuable for China to follow.

Objective To understand the thickness of each section of the pelvic loop and the positions of the peripheral large vessels and nerves, so as to provide evidence for the screw fixation of pelvic fractures. Methods A total of74 normal osseous specimens of the pelvis (male 40 cases, female 34 cases) were selected for the present study. Pelvic center was taken as the dot, and the thickness of the pelvic bone along the pelvis line were measured in the clockwise direction. Thirty 30 CT images of normal pelvis were used to measure the bone thickness of the pelvic loop in the same manner. Moreover, cadaver specimens were also dissected and the position lineof the peripheral largevessels and nerves of the pelvic loop were observed in the clockwise direction. Results (1) The thicknesses (mm) of the pelvic bone along the pelvis line(from 0:00 [12:00] to 6:00) were 25. 36±3. 03 (female 24. 48 ± 2. 16), 32. 59 ± 7. 21 (female 22. 88 ± 2. 13), 24. 06 ± 2. 89 (female 20. 40 ± 2. 07), 44. 12±3. 97(female 37. 55±3. 60), 27. 88±2. 36 (female 22. 68±2. 26), 13. 80±2. 14 (female 10. 22±2. 05), and 15. 04± 2.31 (female 13.53±2.22), respectively; and the results of CT measurement were 25.44±2. 95, 30. 45±7. 14, 24. 49±2. 74, 44. 35±4. 21, 27. 66±2. 12, 14. 06±1. 86 and15. 85 ± 2. 15, respectively. (2) Basedonthe clockwisescale, thepositionsof the main vessels and nerves around the pelvic loop were as follows: the positions of the femoral nerves and the femoral arteries and veins were between 4:00 and 4:30 on the left and between 7:00 and 7:30 on the right; the positions of obturator nerve vesselswere between 4:30 and 5:00 on the left and between 7:00 and 7:30on the right. Conclusion When pelvic center is taken as the dot, it is simple and practical to determine the position of each point of the pelvis and the large vessels and nerves in the clockwise direction. The thickness of each part of the pelvic loop is important to guide screw internal fixation of the pelvic fracture.

Objective: To investigate the diterpenoid alkaloids from Aconitum episcopale. Methods: The obtained compounds were isolated by different chromatographic methods and their structures were identified by physicochemical properties and spectral data. Results: Ten diterpenoid alkaloids were isolated and identified as talatizamine (1), chasmanine (2), crassicauline A (3), foresaconitine (4), acoforestinine (5), yunaconitine (6), 3-deoxy-8-deacetyl-yunaeonitin (7), leucanthumsine D (8), pengshenine B (9), and macrorhynine B (10). Conclusion: Compounds 2-5 and 7-10 are isolated from this plant for the first time.

Objective To evaluate safety and efficacy of a fractional microneedle radiofrequency device in the treatment of axillary osmidrosis.Methods A total of 24 patients with moderate to severe axillary osmidrosis were enrolled from Department of Dermatology of Peking Union Medical College Hospital between June 2015 and June 2016,and treated with the Body TiteTM fractional microneedle radiofrequency device for 1 session.Visual analogue scale (VAS) was used to evaluate the intensity of axillary odor in patients,36-item short-form health survey (SF-36) to assess health-related quality of life (HRQoL),and axillary skin tissues were resected for histopathological examination before and after the treatment.Results VAS showed that 22 of 24 patients achieved persistent remission for more than 12 weeks,and rates of decrease in odor score ranged from 50％ to 100％.However,1 patient experienced recurrence at 12 weeks after the treatment,and another 1 patient did not achieve clinical remission.SF-36 revealed that scores of social functioning (SF),role-emotional (RE) and mental health (MH) scales were all significantly increased after the treatment [M (P0-P100):100.00 (62.00-112.50),100.00 (33.30-110.00),68.00 (48.00-80.00),respectively] compared with those before the treatment [77.50 (62.50-100.00),66.67 (33.30-100.00),55.00 (48.88-72.00),respectively,all P ＜ 0.05].Histopathological examination showed obvious degeneration and necrosis of sweat gland cells in 22 cases,and epidermal damages in 2 patients after the treatment.Unilateral upper-limb pain occurred in 1 case,and small-area burn-like skin changes were observed in 2 cases after the treatment.The postoperative recovery time ranged from 7 to 14 days.Conclusion The fractional microneedle radiofrequency device has shown high clinical response rate,good safety,and favorable application prospects in the treatment of axillary osmidrosis.

A miniaturized potentiometric label-free immunosensor based on the standard complementary metal-oxide-semiconduction transistor(CMOS) process and micro fabrication technique was developed to monitoring diabetes, which could detect the concentrations of glycated hemoglobin (HbA1c) and hemoglobin. This immunosensor includes a micro field-effect transistor based sensor chip integrated with signal readout circuit and a disposable probe electrode. The micro sensor chip was designed by our lab and fabricated by Chartered Semiconductor, Singapore. The disposable probe electrode, which was integrated with sensitive electrodes array and micro reaction pool, was deposited on polyester plastic based on micro fabrication techniques. Antibody of HbA1c and hemoglobin were immobilized on the electrode based on self assemble monolayer and gold nanoparticles. The characteristics of the electrode during modification were studied by cyclic voltammetry and electrochemical impedance technique. The response characteristic of the immunosensor was detected. HbA1c from 4 to 24 mg/L and hemoglobin from 60 to 180 mg/L can be detected by this immunosensor.

Objective To discuss whether Omega-3 fish oil fat emulsion has the potential protective mechanism for 7-day-old rats with hypoxic-ischemic brain damage (HIBD).Methods One hundred and sixty-eight 7-day-old SD rats were randomly divided into 4 groups:group A (sham group),group B (Omega-3 fish oil fat emulsion group),group C (normal fat emulsion group),group D (model group),and there were 42 cases in each group.Neonatal HIBD was induced by the method of Rice.Rats were sacrificed at 1 d,3 d and 7 d after the surgery.Hippocampus was removed for Real-time PCR and Western blot test to detect Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) mRNA and protein expression.TUNEL staining comparison was done among different groups to observe the number of cellular apoptosis.Results HE staining of hippocampus CA1 area in 3 d showed that brain tissues in group A maintained normal structures;those in group D had much more brain cells with severe edema than other groups;TLR4 and NF-κB mRNA and protein expression levels in group D were higher than those in group A in 1 d (all P ＜0.05);TLR4 and NF-κB expression levels of mRNA and protein in group B (4.89 ± 0.51,9.30 ± 1.53;1.15 ±0.10,1.44 ± 0.14) were lower than those in group C (17.58 ± 2.50,20.13 ± 1.00;2.56 ± 0.10,2.82 ± 0.09) and group D (15.94-± 2.52,26.21 ± 3.00;2.34 ± 0.11,4.51 ± 0.36) in 3 d (all P ＜ 0.05),and compared with group A (6.30 ± 1.52,5.32 ± 1.06;1.32 ± 0.10,2.42 ± 0.14),there was significant difference (all P ＞ 0.05);TLR4 and NF-κB mRNA and protein expression levels in group B were lower than those in group C and group D in 7 d(all P ＜0.05),and compared with group A there was no significant difference (all P ＞ 0.05).The apoptotic cell number of brain tissues in 3 d:group B (13.67 ±2.52) were lower than those in group C (27.67 ±2.52) and group D (41.00 ±3.61) (all P ＜0.05),and compared with the group A (6.00 ±2.00),the difference was not statistically significant (P ＞ 0.05).Conclusions Omega-3 fish oil fat emulsion plays an important role in protecting neonatal rats with HIBD.The mechanisms were likely to reduce TLR4,NF-κB and cell apoptosis levels.

Objective To study the characteristics of neonatal sepsis caused by gram positive (G +) bacteria,gram negative (G+) bacteria and fungi.Method Clinical data of 202 neonates with sepsis hospitalized from Jan.2012 to May.2015 were studied.According to the different pathogens,202 neonates were divided into gram positive bacteria group,gram negative bacteria group and fungi group.The general information,clinical manifestation,laboratory examination and treatment outcome of the three groups were analysed with Chi square analysis,LSD,Fisher exact probability tests.Result A total of 202 cases of neonatal sepsis were recruited.The detection rate of gram positive bacteria,gram negative bacteria and fungi was 35.2％ (71 cases),56.4％ (114 cases) and 8.4％ (17 cases),respectively.Comparing with gram negative group and fungi group,gram positive group had older gestational age (36.0 ± 3.8 w,compared with gram negative 33.0 ± 3.9 w,fungi group 31.2 ± 3.2 w,P ＜ 0.05),larger birth weight (2 620 ± 925 g compared with gram negative group 1 999 ± 849 g,fungi group 1 595 ± 666 g,P ＜ 0.05),lower nosocomial infection rate (29.6％ compared with gram negative group 70.2％,fungi group 94.1％,P ＜0.05),lower rate of shock,blood glucose disturbance and thrombocytopenia (P ＜ 0.05).There was no statistics difference between the gram negative group and fungi group.Comparing with the other two groups,fungi group was older [20.0 (11.5,39.5) d compared with gram positive group 7.0 (2.0,17.0) d,and gram negative 10.0 (6.0,18.2) d,P ＜ 0.05].The rate of deep venous catheterization in fungi group was higher than that in gram positive group and gram negative group (88.2％ compared with gram positive group 25.4％,gram negative group 40.4％,P ＜0.05).The treatment course of fungi group was longer than that of the gram positive group and gram negative group [22.0 (12.0,37.5) d compared with the gram positive group 14.0 (10.0,17.0) d,gram negative group 14.0 (11.0,18.0) d,P ＜0.05].The incidence of apnea in the gram negative group was higher than that in gram positive group and fungi group (P ＜ 0.05).The rate of leukocytosis,leukocytopenia and elevated CRP were higher in gram negative and gram positive group (P ＜ 0.05).Conclusion The clinical manifestations and laboratory examinations in neonatal sepsis caused by different pathogens were different,which can help to early identification of different pathogenic infections.However,there is no specific indicators to differentiate neonatal sepsis caused by different pathogens.Early identification of the pathogen needs clinical acumen.

BACKGROUND:Regulatory T cels (Treg) are classified into two subsets, nature Treg (nTreg) and induced Treg (iTreg). Although there is consensus that CD4+CD25+FoxP3+CD127-is the widely accepted phenotype of Treg, it remains unclear what is the difference in phenotypes including cytokine patterns of nTreg and iTreg. OBJECTIVE:To understand and compare the plasticity of nTreg and iTreg and to search the exact mechanism of cytokine secretion in Tregs. METHODS: We investigated the frequency and cytokine pattern of CD4+CD25+FoxP3+CD127-nTreg in freshly separated peripheral blood mononuclear cels of five healthy individuals using 8-color fluorescence flow cytometry (FACSCanto II). Subsequently, after 9 days of alostimulation in mixed lymphocytes, the frequency and cytokine pattern of CD4+CD25+FoxP3+CD127-iTreg were determined and analyzed. RESULTS AND CONCLUSION:In fresh cels, (1.5±0.70)% of CD4+ T cels were CD4+CD25+FoxP3+CD127- nTregs. Almost al these cels expressed interferon (IFN)-γ-, interleukin (IL)-2- or transforming growth factor-β+, and partial cels expressed IL-10+ or IL-10-. After 9-day alostimulation, the number of CD4+CD25+FoxP3+CD127- iTreg expressing IFN-γ+, IL-2-, IL-2+, IL-10+ or TGF-β+increased strongly. The main subsets of human nTregs were CD4+CD25+FoxP3+CD127-IFN-γ-IL-2-IL-10+TGF-β+and CD4+CD25+FoxP3+CD127-IFN-γ-IL-2-IL-10-TGF-β+ T cels. The proportion of each subset in CD4+ T cels was (1.1±0.59)% and (0.39±0.16)%, respectively. Whereas the main subsets of human iTregs were CD4+CD25+FoxP3+CD127-IFN-γ+IL-2-IL-10+TGF-β+ and CD4+CD25+FoxP3+CD127-IFN-γ+IL-2+IL-10+TGF-β+. Human nTregs were characterized as IFN-γ-IL-2- double negative, producing IL-10 and TGF-β or only TGF-β without IL-10, and not proliferatingin vitro. During the alostimulation in mixed lymphocytes, IFN-γ+ iTregs proliferated remarkably. One-third of IFN-γ+ iTreg expressed IL-2+, and two-thirds of IFN-γ+ iTregs expressed IL-2, both of which produce IL-2 and TGF-β. Our results imply that CD4+CD25+FoxP3+CD127- Treg are potentialy immunosuppressive probably because of their mandatory TGF-β and optional IL-10 production.

Objective To explore the biocompatibility of nano-hydroxyapatite/polyamide 66 (nHA/PA66) with human bone mesenchymal stem cells (hBMSCs) after osteogenic induction.Methods After hBMSCs were isolated and cultured in vitro,the experiment was conducted in 3 groups.Group A were hBMSCs subjected to no osteogenic induction,group B hBMSCs subjected to osteogenic induction,and group C was the composite of nHA/PA66 with hBMSCs subjected to osteogenic induction.Adhesion of the cells onto the nHA/PA66 in group C was observed by electron microscope scanning.Growth and proliferation of the cells in groups B and C were detected by MTI test at 1,2 and 3 weeks.The ability of osteogenic differentiation of hBMSCs in vitro was analyzed by alkaline phosphatase (ALP) activity and alizarin red staining.The ability of osteogenic differentiation of hBMSCs on nHA/PA66 was tested by ALP activity.Results Electron microscope scanning showed that the cells spread and attached well on the surface of the composite scaffold in group C;the proliferation of the cells in groups B and C showed no significant difference (P ＞ O.05).These suggested that the proliferation of hBMSCs was not affected by nHA/PA66.The number of mineralized nodules in group B was significantly larger than in group A (P ＜ O.05);the ALP activity of the cells in group A was significantly lower than in group B at 6 and 12 days (P ＜ 0.05);no significant differences were observed between groups B and C (P ＞ 0.05).These indicated that the hBMSCs were capable of osteogenic differentiation which was not affected by nHA/PA66.In groups B and C,the ALP activity of the cells at 12 days was significantly higher than at 6 days,indicating the ALP activity increased with increased induction time (P ＜ 0.05).Conclusion nHA/PA66 can be used as a carrier of hBMSCs in bone tissue engineering because hBMSCs can well adhere to,proliferate,and differentiate into bone on nHA/PA66 scaffolds.