Analysis on Innovation Input-output in China ’s Pharmaceutical Enterprises from the Perspective of Patent Appli- cation / 中国药房

OBJECTIVE：To provide reference for optimizing resource allocation and precise investment of China ’s pharma- ceutical industry. METHODS ：The number of invention patent applications in China ’s pharmaceutical industry was searched from China Intellectual Property Netwerk ，and the status quo and structure of patent applications in China ’s pharmaceutical industry were analyzed. SPSS 23.0 software was used to analyze the input-output correlation of the number of invention patent applications with R&D investment and main business income of pharmaceutical enterprises in China. RESULTS ：The number of invention patent applications in China ’s pharmaceutical industry increased year by year. From 2000 to 2015，225 861 invention patents had been applied by domestic applicants and 43 149 invention patents had been applied by foreign applicants in China ；only 49.94％ domestic applicants applied for professional invention ，while 96.79％ of foreign applicants applied for professional invention. There was a positive correlation between the R&D expenditure of pharmaceutical enterprises and the number of invention patent applications，which indicated that the R&D investment of pharmaceutical industry in China was beneficial to the invention patent applications. The number of invention patent applications of pharmaceutical enterprises was also positively correlated with the main business income ，indicating that the increase of invention patent applications of pharmaceutical enterprises also effectively expanded the economic scale of pharmaceutical industry. CONCLUSIONS ：Compared with foreign countries ，the structure of patent applicants in domestic pharmaceutical industry needs to be adjusted urgently. Pharmaceutical enterprises have not yet become the main applicants. The continuous R&D investment of pharmaceutical enterprises effectively promotes the application of invention patent，expanded the economic scale of the pharmaceutical industry.

The effects of LED blue light tube phototherapy in the treatment of acute bilirubin encephalopathy / 中国新生儿科杂志

Objective To study the clinical efficacy of LED blue light tube phototherapy in severe hyperbilirubinemia with acute bilirubin encephalopathy (ABE).Method Clinical data of newborns admitted to neonatal department of our hospital between Dec.2013 and Dec.2016 were retrospectively reviewed.Infants with gestational age ≥ 35 weeks who were diagnosed with severe hyperbilirubinemia and ABE were collected and analyzed.From Dec.2013 to Nov.2014,infants treated with common blue light tube were assigned into traditional blue light group (traditional group).From Dec.2014 to Dec.2016,infants treated with LED blue light tube were assigned to LED blue light group (LED group).Total serum bilirubin (TSB) levels and bilirubin induced neurological dysfunction (BIND) scores were analyzed between the two groups.Neuron specific enolase (NSE) levels before and after phototherapy were also compared.Follow-up data for three months after discharge were analyzed.Result Fifty-one infants with severe hyperbilirubinemia and ABE were included,with 24 cases in traditional group and 27 cases in LED group.There were no significant differences in TSB levels and BIND scores between the two groups before phototherapy (P ＞ 0.05).TSB levels at 4 h,24 h and 48 h after phototherapy in LED group were significantly lower than traditional group respectively [(331.3 ±21.8) μmol/L vs.(372.1 ±25.2) μmol/L,(233.6 ± 20.4) μmol/L vs.(269.4 ± 19.8) μmol/L,(184.5 ± 15.2) μmol/L vs.(226.3 ± 22.7) μmol/L,P ＜ 0.05].However,there was no significant difference in TSB levels at 12 h after phototherapy between the two groups (P ＞ 0.05).BIND scores at 4 h after phototherapy in LED group were significantly lower than traditional group [(4.0 ± 0.6) vs.(4.7 ± 0.8),P ＜ 0.05].There were no significant differences in BIND scores at other time points after phototherapy between the two groups (P ＞ 0.05).In both groups,serum NSE levels after phototherapy were lower than before phototherapy.Serum NSE level after phototherapy in the LED group was significantly lower than the traditional group (P ＜ 0.05).Total phototherapy duration of the LED group was significantly shorter than the traditional group (P ＜ 0.05).The incidence of exchange transfusion in LED group was significantly lower than traditional group.The incidence of abnormal brainstem auditory evoked potential in LED group were significantly lower than traditional group at 1 month and 3 months after birth (P ＜ 0.05).The proportion of abnormal cranial MRI between the two groups showed no statistical differences (P ＞ 0.05).Conclusion TSB levels and brain injury indicators should be closely monitored and evaluated in infants with severe hyperbilirubinemia and ABE.Active LED blue light phototherapy can rapidly reduce TSB levels,effectively control the progress of ABE,and reduce the ratio of exchange transfusion.Adverse reactions of LED blue light phototherapy are not observed in this study.

Comparison of baroreflex sensitivity during sevoflurane-versus isoflurane-induced controlled hypotension in pediatric patients / 中华麻醉学杂志

Objective To compare the baroreflex sensitivity (BRS) when controlled hypotension was performed with sevoflurane versus isoflurane in the pediatric patients.Methods Sixty male American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 3-16 yr,with body mass index of 20-28 kg/m2,scheduled for elective scoliosis surgery under general anesthesia,were randomly divided into 2 groups (n=30 each) using a random number table:sevoflurane-induced hypotension group (group Sev) and isoflurane-induced hypotension group (group Iso).Anesthesia was induced with midazolam,sufentanil and propofol.Endotracheal intubation was facilitated with rocuronium.Anesthesia was maintained with closed-circuit low flow anesthesia with either sevoflurane or isoflurane,maintaining mean arterial pressure at 55-65 mmHg and bispectral index values at 40-60 during surgery.Cardiovascular BRS was measured before induction of anesthesia (T0),immediately after intubation (T1),immediately after the end-tidal inhalational anesthetic concentration reached 1 minimal alveolar concentration (T2),and at 10,20 and 30 min after target hypotension (mean arterial pressure 55-65 mmHg) was achieved (T3-5).Results There was no significant difference in BRS at T0-2 between the two groups (P＞0.05).Compared with the value at To,the BRS was significantly decreased at the other time points in the two groups (P＜0.05).Compared with the value at T1,the BRS was significantly increased at T2,and decreased at T3-5 in the two groups (P＜0.05).The BRS was significantly lower at T3-5 than at T2 in the two groups (P＜0.05).The BRS was significantly lower at T3-5 in group Sev than in group Iso in the two groups (P＜0.05).Conclusion Sevoflurane produces better efficacy than isoflurane when used for controlled hypotension in the pediatric patients.

Research on Patent Behaviors of 7 Chinese Pharmaceutical Demonstration Enterprises for Intellectual Property / 中国药房

OBJECTIVE:To study the characteristics of patent behaviors of Chinese pharmaceutical demonstration enterprises for intellectual property,and to provide reference for the improvement of patent behaviors in Chinese pharmaceutial enterprises. METHODS:After retrieving the applicants(patentees)from China Intellectual Property Right Net on the basis of taking 7 pharma-ceutical demonstration enterprises chosen through appraisal by State Intellectual Property Office of the P.R.C in 2013 as the study samples,empirical study was conducted on their patent behaviors during 1985 and 2013,including the number and type of the pat-ents for which applications were made,international patent classification and legal status. RESULTS:The number of patent applica-tions of the 7 pharmaceutical demonstration enterprises demonstrated a growing trend(an annual increase up to 79.0%). The appli-cations were dominated by the inventive patent(84.9%). Many patents were in an authorized legal status(46.7%). All of these en-terprises paid more attention to the maintenance of the authorized patent. The technology patent applications were mainly about chemical compound,composition,and preparation methods,including the technical proposal containing the active ingredients and properties of the pharmaceutical preparation (A61K),particularly the application of the technical proposal related to the treatment with the preparation (A61P). CONCLUSIONS:All the 7 pharmaceutical demonstration enterprises were aware of patent competi-tion and protection and characterized by a higher proportion of the application for the inventive patent,perfect patent information management institution and high-quality patent applications. Chinese pharmaceutical enterprises can enhance their competitiveness and creativity through adjusting patent behaviors and increasing their awareness of patent competition.

Analysis of risk factors of late preterm infants with hyperbilirubinemia / 临床儿科杂志

Objective To explore the risk factors of hyperbilirubinemia in late preterm infants. Methods Clinical data of 211 cases of late preterm infants with hyperbilirubinemia and 246 cases of late preterm infants without hyperbilirubinemia were retro-spectively analyzed between 2011 and 2012. The risk factors of hyperbilirubinemia were filtered. Results Twenty-seven cases of late premature infants with hyperbilirubinemia were severe. Hospital stay less than 3 days, birth asphyxia history, small for gestatio-nal age, head hematoma, delivery injury, hypoalbuminemia, polycythemia, infection, hemolytic disease, feeding intolerance, and fe-tal excretion delay were associated with hyperbilirubinemia (P<0.05). Rural origin, pregnancy-induced hypertension syndrome and premature rupture of membrane were also associated with hyperbilirubinemia (P<0.05). Multivariate logistic regression analysis showed the history of birth asphyxia , fetal excretion delay, hypoalbuminemia, pregnancy-induced hypertension syndrome were risk factors of hyperbilirubinemia in late preterm infants (OR=2.35-4.05). Pregnancy-induced hypertension syndrome and hemolytic dis-ease were risk factors of severe hyperbilirubinemia in late preterm infants (OR=5.74, 73.64). Conclusions Neonatal asphyxia, fetal excretion delay, hypoalbuminemia and pregnancy-induced hypertension syndrome are risk factors of hyperbilirubinemia in late pre-term infants. Strengthening the management of pregnancy-induced hypertension syndrome and the treatment of newborn hemolytic disease can reduce the occurrence of severe hyperbilirubinemia in late preterm infants.

Gene Cloning, Expression and Immunogenicity of the Protective Antigen Subolesin in Dermacentor silvarum

Subolesin (4D8), the ortholog of insect akirins, is a highly conserved protective antigen and thus has the potential for development of a broad-spectrum vaccine against ticks and mosquitoes. To date, no protective antigens have been characterized nor tested as candidate vaccines against Dermacentor silvarum bites and transmission of associated pathogens. In this study, we cloned the open reading frame (ORF) of D. silvarum 4D8 cDNA (Ds4D8), which consisted of 498 bp encoding 165 amino acid residues. The results of sequence alignments and phylogenetic analysis demonstrated that D. silvarum 4D8 (Ds4D8) is highly conserved showing more than 81% identity of amino acid sequences with those of other hard ticks. Additionally, Ds4D8 containing restriction sites was ligated into the pET-32(a+) expression vector and the recombinant plasmid was transformed into Escherichia coli rosetta. The recombinant Ds4D8 (rDs4D8) was induced by isopropyl beta-D-thiogalactopyranoside (IPTG) and purified using Ni affinity chromatography. The SDS-PAGE results showed that the molecular weight of rDs4D8 was 40 kDa, which was consistent with the expected molecular mass considering 22 kDa histidine-tagged thioredoxin (TRX) protein from the expression vector. Western blot results showed that rabbit anti-D. silvarum serum recognized the expressed rDs4D8, suggesting an immune response against rDs4D8. These results provided the basis for developing a candidate vaccine against D. silvarum ticks and transmission of associated pathogens.

Screening and Molecular Cloning of a Protective Antigen from the Midgut of Haemaphysalis longicornis

Vaccination is considered a promising alternative for controlling tick infestations. Haemaphysalis longicornis midgut proteins separated by SDS-PAGE and transferred to polyvinylidene difluoride (PVDF) membrane were screened for protective value against bites. The western blot demonstrated the immunogenicity of 92 kDa protein (P92). The analysis of the P92 amino acid sequence by LC-MS/MS indicated that it was a H. longicornis paramyosin (Hl-Pmy). The full lenghth cDNA of Hl-Pmy was obtained by rapid amplification of cDNA ends (RACE) which consisted of 2,783 bp with a 161 bp 3' untranslated region. Sequence alignment of tick paramyosin (Pmy) showed that Hl-Pmy shared a high level of conservation among ticks. Comparison with the protective epitope sequence of other invertebrate Pmy, it was calculated that the protective epitope of Hl-Pmy was a peptide (LEEAEGSSETVVEMNKKRDTE) named LEE, which was close to the N-terminal of Hl-Pmy protein. The secondary structure analysis suggested that LEE had non-helical segments within an alpha-helical structure. These results provide the basis for developing a vaccine against biting H. longicornis ticks.

The correlation factor analysis of the neonates abandoned in hospital less than 24 hours / 中国小儿急救医学

Objective To investigate the relative factors of the neonates that were abandoned in hospital less than 24 hours,then the level of the local neonates medical service and the neonatal remedy skills and the life quality could be improved.Methods The clinical data of 379 cases of hospitalized neonates less than 24 hours from 2007 to 2011 were analyzed retrospectively.The correlation factors of the neonates abandoned in hospital less than 24 hours(122 cases) and hospitalized more than 24 hours (244 cases) were analyzed by single and multiple factor regression analysis.Results (1) There were 379 neonates who were in hospital less than 24 hours,among them,122 neonates were gave up the treatments.The differences of the gestational age and weight among abandon group,hospital referral group,improve group and uncured group were significant(P ＜0.01).(2) The numbers of neonates abandoned in hospital less than 24 hours were different significantly from 2007 to 2011 (P ＜0.05) and tendency was decreased year by year(chi-square trend test x2 =6.115,P =0.013).The uncured group was increased year by year (P ＜ 0.05).The hospital referral group,improved group were fluctuation,but no descend or rise tendency(P ＞0.05).(3) The differences of the gestational age,birth weight,uterine-incision delivery,intrapartum asphyxia,intrauterine distress,birth hospital,family income less than twenty thousand yuan every year,father's culture level,diagnosed premature,very low birth weight infant,low birth weight infant,respiratory distress syndrome and brain injuries were significant between neonates in hospital less than 24 hours and more than 24 hours(P ＜ 0.05).The differences of the male,intrapartum high risk factors,mother's morbid state and miscarriage were not significant(P ＞0.05).(4) The uterine-incision delivery,intrapartum asphyxia,birth in the county and below county hospital,family income less than twenty thousand yuan every year and diagnosed respiratory distress syndrome were correlation to the abandon treatment in 24 hours.There were no correlation to the gave up treatment in 24 hours to the rest of the factors.Conclusion We should set up the systemic gravid detection system,avoid premature birth and respiratory distress syndrome,add the hardware configuration and medical personnel to the neonate department,improve the professional technology level,perfect social security system mechanism,decrease the hospital discharge rate of the hospitalization less than 24 hours,improve the level of the local neonatal treatment technology and the quality of population.

Discussion on the SCM of the Pharmaceutical Enterprises in China / 中国药房

OBJECTIVE:Discussion on the improvement of pharmaceutical enterprises competence by the practice of sup?ply chain management(SCM)in China.METHODS:Combing current situation,to analyse the requirement for the practice of SCM in China.RESULTS&CONCLUSION:It will be the key of raising the competence of pharmaceutical enterprises in China to establish integrating idea,optimize the system of SCM,reform the flow channel of pharmaceutical commodities and establish new system of assessment.

On Sampling Test of Drugs in China / 中国药房

OBJECTIVE:To discuss problems concerning the current sampling test of drugs in China.METHODS:The rationality of the current drug sampling test method was analyzed empirically according to the theory of sampling test.RESULTS&CONCLUSION:The current drug sampling test method is far from perfect and by which the quality of drugs was unable to be effectively controlled.It is recommended that drug monitoring institutions should work out more scientific sampling test scheme so as to ensure the quality of drugs.