Analysis on the difference between the payment limitations of anti-cancer drugs and the application scope of drug indications / 中国药房

OBJECTIVE To analyze the difference between the payment limitations of anti-cancer drugs and application scope of drug instructions， so as to better implement the payment policy of medical insurance drugs. METHODS The differences between the payment limitations of anti-cancer drugs and application scope of drug instructions in the National Catalogue of Drugs for Basic Medical Insurance， Industrial Injury Insurance and Maternity Insurance （2022） were compared and analyzed； the evidence-based basis of the difference was discussed， and the scope of limited payment was interpreted. RESULTS Totally 118 drugs had payment limitations； limitations scope mainly included limited evidence of gene detection results， limited indications， limited second-line and above treatment， limited payment duration， limited specialist prescription， limited medical institution grade， etc. Among them， 43 drugs had differences between the payment limitations and drug instructions， and the indications of 31 drugs were greater than payment limitations； for seven drugs， the drug indications beyond the payment limitations were recommended by the guidelines. The payment limitations of 75 drugs were consistent with drug instructions. The second-line and multi-line treatment was ineffective or intolerable with first-line drugs. There was a certain relationship between locally advanced， advanced or metastatic tumor and tumor stage， but different tumors had different criteria. Systemic treatment mainly referred to systemic treatment with drug. The results of limited genetic test required that the result was positive or negative. In addition， six kinds of TCM injections were limited to the level of medical institutions； the payment of two drugs did not exceed 12 months； when lenalidomide was combined with isazomide citrate， the medical insurance only paid for one of the drugs. CONCLUSIONS The payment limitations of some anti- cancer drugs are inconsistent with the drug indications. The drug payment limitations should be expanded according to the actual situation of clinical medication and the recommendations of guidelines. At the same time， the payment limitations should be formulated accurately and in detail， thus clinical and medical insurance staff can understand it and fully protect the interests of patients.

Newborn screening, gene variation analysis and follow-up study of very long chain acyl CoA dehydrogenase deficiency / 中华实用儿科临床杂志

Objective:To investigate the prevalence, gene variation and prognosis of very long chain acyl CoA dehydrogenase deficiency (VLCADD) in newborns in Henan Province.Methods:From January 2013 to December 2019, 867 103 newborns were investigated for VLCADD by tandem mass spectrometry.Children who diagnosed as VLCADD and their families were subjected to next-generation sequencing and Sanger sequencing.Clinical data, biochemical changes and gene variation characteristics of the confirmed cases of VLCADD were analyzed.Dietary guidance was given, and their growth and development were followed up.Results:Six neonates were diagnosed as VLCADD, and the prevalence of VLCADD in the Henan Province was 1/144 517.A total of 11 mutations in the ACADVL gene were found, including 5 new variants c. 692-2_692-1delAG, c.753-23_753-22del, c.960delG, c.1361A>G, and c. 1955C>T.The newborns were given a high-carbohydrate, low-fat diet, and followed up for 8-56 months.Except for two deaths, all patients had a good outcome. Conclusions:The prevalence of neonatal VLCADD in Henan Province is 1/144 517.This results has enriched the ACADVL gene mutation spectrum and provided an important basis for the screening and diagnosis of VLCADD.

Mutation analysis of patients with 6-pyruvoyltetrahydropterin synthase deficiency in Henan / 中华实用儿科临床杂志

Objective:To analyze the variation and characteristics of gene mutation in patients with 6-pyruvoyltetrahydropterin synthase deficiency(PTPSD) in Henan province, and to provide the theoretical basis for early diagnosis, treatment, genetic consultation and prenatal diagnosis of PTPSD.Methods:One thousand nine hundred and six children with hyperphenylalaninemia (HPA) treated in Henan Neonatal Screening Center, the Third Affiliated Hospital of Zhengzhou University from January 1998 to December 2018 were included.Chemiluminescence was used for pheny-lalanine (Phe) detection in blood or dried blood spots.For patients with Phe concentration >120 μmol/L, urine pterin analysis was carried out, and the activity of dihydropteridine reductase (DHPR) was detected.Mutations of the PAH, GCH1, GFRP, PCBD1, PTPS and QDPR in 79 children with tetrahydrobiopterin deficiency(BH4D) were detected by using the high-throughput sequencing.All variations were verified by Sanger sequencing. Results:Among the 1 906 children, 79 cases were diagnosed as BH4D clinically, and they all were PTPSD.The incidence of PTPSD in HPA in Henan was 4.14%.One hundred and fifty-six out of 158 alleles in 79 children were detected, and the detection rate of gene mutation was 98.73%, 30 mutations were identified and most of the variants were located in exons 5(92/156 cases, 58.97%). Variants of c. 259C>T (61/156 cases, 39.10%), c.286G>A (17/156 cases, 10.90%), c.155A>G (13/156 cases, 8.33%) and c. 272A > G (10/156 cases, 6.41%) were more common.Six novel variations were detected, which included c. -77G>T, c.158A>G, c.262C>T, c.207G>A, c.316A>G and c. 332C>G; 38 genotypes had been identified, including 3 homozygous mutations and 33 compound heterozygous mutations.Conclusions:c. 259C>T is the hot-spots gene mutation in Chinese PTPSD patients in Henan province.The identification of 6 new mutations enriches the gene mutation profile.

Clinical and genetic characteristics of primary carnitine deficiency identified by neonatal screening / 中华医学遗传学杂志

Objective@#To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD).@*Methods@#From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up.@*Results@#In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c. 1484T>C, c. 394-1G>T, c. 431T>C and c. 265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c. 1400C>G (42.3%), c. 760C>T (11.5%) and c. 51C>G (7.7%). During the 8 ~ 42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment.@*Conclusion@#The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c. 1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.

Meta-analysis of the Effectiveness of Trolamine for Preventing and Treating Radiation Dermatitis and Quality Evaluation of GRADE Evidence / 中国药房

OBJECTIVE： To evaluate the effectiveness of trolamine for preventing and treating radiation dermatitis （RD） and evidence quality， and to provide reference for clinical use. METHODS： Retrieved from PubMed， Cochrane library， Embase， CNKI， Wanfang and VIP database， randomized controlled trials （RCTs） about trolamine （trial group） versus usual care （control group） for preventing and treating RD were collected. After data extraction， Cochrane bias risk assessment tool 5.0.2 was used to assess the bias risk， and Rev Man 5.3 statistical software was used to perform the Meta-analysis. GRADE evidence quality grading system was used to evaluate the evidence quality of outcome indexes. RESULTS： Seven RCTs were included， involving 782 patients. Results of Meta-analysis showed that there was no statistical significance in total incidence of RD [OR＝0.50， 95％CI （0.23， 1.11）， P＝0.09]， and the incidence of grade Ⅰ RD [OR＝1.32， 95％CI（0.96，1.81）， P＝0.09]， grade Ⅱ RD [OR＝1.07， 95％CI（0.80，1.42）， P＝0.66]， grade Ⅲ RD [OR＝0.69， 95％CI（0.45，1.04）， P＝0.07] or grade Ⅳ RD [OR＝0.43， 95％CI（0.17，1.05）， P＝0.07] between 2 groups. Results of Grade evidence quality evaluation showed that total incidence of RD， and the incidence of grade Ⅱ RD and grade Ⅳ RD were recommended by moderate-level evidence in 2 groups， while the incidence of grade Ⅰ and grade Ⅲ RD were recommended by low-level evidence. CONCLUSIONS： Trolamine is not effective in preventing and treating RD， and can not reduce the incidence of RD.

Clinical and genetic characteristics of primary carnitine deficiency identified by neonatal screening / 中华医学遗传学杂志

OBJECTIVE@#To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD).@*METHODS@#From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up.@*RESULTS@#In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c.1484T>C, c.394-1G>T, c.431T>C and c.265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c.1400C>G (42.3%), c.760C>T (11.5%) and c.51C>G (7.7%). During the 8-42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment.@*CONCLUSION@#The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c.1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.

Application of genome engineering in medical synthetic biology / 生物工程学报

Synthetic biology aims to establish a complete set of engineering principles, theories, and methods, via the rational design and assembly of basic biological parts, for the goal of effective implementation of complex biological systems with programmable functions. In recent years, with emerging novel classes of programmable genetic parts, in particular, the establishment and optimization of CRISPR and CRISPRi technology platforms, synthetic biology is entering a new era. This review summarizes recent advances on CRISPR genome editing and gene regulation technologies, their applications in constructing programmable biological parts, and their roles in building sophisticated gene circuits. We also provide a future vision on how synthetic biology can transform medicine (named medical synthetic biology, MSB) and therapeutics.

PTPS gene analysis and prenatal diagnosis in patients with 6-pyruvoyl-tetra hydropterin synthase deficiency / 中华妇产科杂志

Objective To analyze the variations of PTPS gene in patients with suspected 6-pyruvoyl-tetra hydropterin synthase deficiency (PTPSD) and to make prenatal diagnosis in high-risk families. Methods Chemiluminescence was used for phenylalanine detection in blood or dried blood spots.Patients with phenylalanine concentration over 120μmol/L were detected by urine pterin analysis, and the activity of dihydropteridine reductase (DHPR) was detected. tetrahydrobiopterin loading tests were performed in suspected patients with abnormal urinary pterin profiles. PTPS gene variation analysis was performed by direct Sanger sequencing based on PCR amplification. Prenatal diagnosis in 7 high-risk families was performed by chorionic villus sampling when the genotype was identified. Results In 656 patients with hyperphenylalanine, 22 cases were diagnosed as PTPSD clinically. 16 variations were detected in the 22 PTPSD cases. The 5 variations, p.Lys77Arg, p.Ile84Phe, c.315-2A>G, c.244-2A>T, c.187-1G>T, were identified as novel variations. Two fetuses carried the same mutation with the proband and therefore were thought to be PTPSD fetuses. Three fetuses carried only one mutant allele and thus were thought to be PTPSD carriers.

Establishment and Application of Pharmaceutical Care Pathway for the Anti-tumor Drugs / 中国药房

OBJECTIVE:To provide the new idea for clinical pharmacists providing pharmaceutical care in oncology depart-ment. METHODS:Applying the principles and methods of clinical pathway,the pharmaceutical care of anti-tumor drugs could be divided into before medication,during medication,after medication and patient education,according to the sequence of taking med-icine. On the basis of evidence-based medicine,the care contents of each unit were established,and the pharmaceutical care path-way (PCP) was formed. During chemotherapy duration for a breast cancer metastasis patient with liver function injury,clinical pharmacists conducted pharmaceutical care for drug pretreatment,ADR monitoring and disposal,patient education,as well as put forward the proposal of drug treatment as supplementing calcium,adjusting the dose of epirubicin and paclitaxel targeting on PCP of zoledronic acid,epirubicin and paclitaxel. RESULTS:Physicians adopted the pharmacist’s recommendations. The patient suf-fered from joint and muscle pain during chemotherapy,and the symptom was relieved after symptomatic treatment by celecoxib;chest and back discomfort was relieved significantly after chemotherapy,and the disease condition kept stable. The patient was dis-charged from the hospital. CONCLUSIONS:PCP focus on the time,content and countermeasures of pharmaceutical care,the pro-gram and treatment results of pharmaceutical care,and promote standardization,formalization,simplification and procedure of pharmaceutical care. Clinical pharmacists conduct individualized pharmaceutical care rapidly targeting on PCP so as to deepen the communication of clinical pharmacists with physicians,nurses and patients,and promote the development of pharmaceutical care smoothly.

Genotype and phenotype correlation of phenylalanine hydroxylase deficiency among patients from Henan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To delineate the mutation spectrum of phenylalanine hydroxylase (PAH) gene among patients affected with phenylalanine hydroxylase deficiency (PAHD) in Henan Province of China, and to explore the correlation between the genotype and the phenotype.</p><p><b>METHODS</b>A total of 155 affected children were recruited. Potential mutation of the PAH gene were analyzed by direct sequencing. The genotype-phenotype correlation was analyzed by matching the expected and observed phenotypes.</p><p><b>RESULTS</b>Over 72 mutations and 108 genotypes have been identified. There were 7 homozygous mutations, including 1 case with EX6-96A>G/EX6-96A>G, 1 with R241C/R241C, 1 with R413P/R413P, and 4 with R243Q/R243Q. Among these, 6 patients have presented classic PKU phenotypes, except for a R241C/R241C genotype which has led to mild PKU. In 104 patients carrying compound PAH mutations, 52 were classic, 34 were mild and 39 had mild HPA. Patients who were heterozygous for EX6-96A>G/R241C, R243Q/A434D, EX6-96A>G/R413P and EX6-96A>G/ R241C were found with both the classic PKU and mild PKU phenotypes. Common mutations associated with mild HPA have included R53H, R243Q, V399V and H107R. The common mutations associated with mild PKU included R243Q, R241C, EX6-96A>G, and IVS4-1G>A. The prevalent mutations in classic PKU were R243Q, EX6-96A>G and V399V. The consistency between prediction of the biochemical genotype and observed phenotype was 77.78%, especially in classic PKU, the consistency was up to 82.14%. Significant correlations were disclosed between pretreatment levels of phenylalanine and AV sum (r=-0.6729, P < 0.01).</p><p><b>CONCLUSION</b>The mutation spectrum of PAH gene in Henan seems to differ from that of other regions. Independent assortment of mutant alleles may result in a complex genotype-phenotype correlation, but the genotypes of PAHD patients have correlated with the phenotype.</p>

PHARMACOKINETICS OF SITE-SPECIFIC DELIVERY OF DEXAMETHASONE-DEXTRAN PRODRUG IN RAT GASTROINTESTINAL TRACT / 药学学报

AIM　To explore whether dexamethasone-dextran (260 000) has the characteristics of site-specific delivery in rat gastrointestinal tract. METHODS　Dexamethasone prodrug and dexamethasone were administered to rat ig at the dose of 5 μmol*kg-1. The distribution of dexamethasone in the contents and mucosa of different parts of the rat GI tract at different time intervals and its concentration in plasma were determined by HPLC. RESULTS　Dexamethasone was mainly released in the cecum and colon contents and mucosa after oral administration of dexamethasone prodrug. The absorption was reduced significantly. The peak time of the drug in plasma was 8.1 h, and the peak concentration was 32 μg*L-1. However, free dexamethasone was found mainly in the contents and mucosa of the stomach, proximal and distal small intestine. The peak time of the drug in plasma was 2.2 h, and the peak concentration was 2120 μg*L-1. CONCLUSION Dexamethasone can be specifically delivered to the large intestine by using dexamethasone-dextran (260 000). It appears that the prodrug has a potential in the treatment of inflammatory bowel disease.

Key technology of the methodology of fingerprints-pharmacy of traditional Chinese medicines (F-P of TCMs) / 中成药

This paper summarised related investigations, literature and theoretical and experimental achievements in the field, describing key technology of the methodology of F P of TCMs. The scientific, progressive, practical and feasible significance is discussed.

EFFECT OF Mn9202 ON 5-HT, TH AND 5-HT RECEPTOR OF CULTURED RAT STOMACH FUNDUS SMOOTH MUSCLE CELLS / 解剖学报

Objective To study the effects of DHPs calcium antagonist Mn9202 and lacidipine on 5-HT、TH and 5-HTR of rat stomach fundus smooth muscle cells. Methods It's effects was investigated by using immunocytochemistry and image analysis of stom- ach fundus smooth muscle cells in culture and compared with cyprohetadine(antagonist of 5-HT). Results 5-HT、TH and 5-HTR im- munoreactive substances were existed in SFSMC. The results of image analysis indicated that the content of 5-HT. TH and 5-HTR were significantly lower when using Mn9202.lacidipine and cyprohetadine. Conclusion The results suggest that the rat stomach fundus smooth muscle cells possess 5-HT autocrine function, and DHPs calcium antagonist reduce the number of 5-HT receptor in the rat stomach fundus smooth muscle cells though the reduction of 5-HT sythesis, this results conform with cyprohetadine (antagonist of 5 - HT).

Hypoxia-reoxygenation induced apoptosis of cardiomyocytes and the effect of nitric oxide / 中国药理学通报

AIM To study hypoxia reoxygenation induced apoptosis of neonatal rat cardiomyocytes and the roles of nitric oxide in this process. METHODS Cultured neonatal rat cardiomyocytes were divided into two groups. Cells of one group were cultured in an incubator of 950 mL?L -1 N 2 and 50 mL?L -1 CO 2 for 16 h, 32 h and 48 h followed by normal incubation for 6h to form the cell model of hypoxia reoxygenation injury.Cells of another group were cultured in the same hypoxia condition for 16 h, 32 h and 48 h. Before they were put in normal condition for 6 h, NO donor SNAP was added to the media to form the final concentration of 100 ?mol?L -1 . Apoptosis was detected by TUNEL and flow cytometer. RESULTS Apoptotic cells were detected by TUNEL after hypoxia of 16 h, 32 h and 48 h followed by 6 h reoxygenation and the apoptotic rates of cardiomyocytes were (5 5?0 7)%, (11 0?1 1)% and (14 2?1 6)% respectively detectedby flow cytometer. The apoptotic rates of myocardiums with SNAP were (3 2?0 7)%, (7 8?0 7)% and (10 9?1 0)% respsctively. CONCLUSION The apoptotic rates of cardiomyocytes undergoing hypoxia reoxygenation injury increase with time of hypoxia; NO can inhibit apoptotic rates of cardiomyocytes in this pathological process and thus may have a protective effect on cardiomyocytes.

The effects of IHC-72 on arrhythmia and lipid peroxides of ischemia and reperfusion rat hearts in vivo / 中国药理学通报

Acute myocardial ischemia and reperfusion led to arrhythmias and increase of glutamic oxalacetic transaminase (GOT),lactate dehydrogenase (LDH),non-csterified fatty acid (FFA) and malondialdehyde (MDA) content, and decrease of superoxide dismutase (SOD) activity in rats. 3, 6-di-methylamino-dibenzopyri-odonium edetate (IHC-72) 5 mg?kg-1 iv significantly reduced the incidence of ventricular tachy-cardia (VT) and ventricular fibrillation(VF) ,shortened the duration of arrhythmias induced by reperfusion, decreased the release of GOT, LDH and FFA, obviously reduced the MDA content,and effectively protected SOD activity in ischemia-reperfused rat hearts. Our experimental results suggested that IHC-72 had protective effects on ischemia-reperfusion injury rat hearts in vivo. The mechanism of the protection might be associated with the inhibition of cellular lipid peroxidation.

EFFECTS OF NICORANDIL ON PHYSIOLOGICAL PROPERTIES OF GUINEA PIG PAPILLARY MUSCLES / 中国药理学通报

The effects of nicorandil ( NICO ) on the contractility, automati -city, excitability, functional refractory period ( FRP ) & dose-response curves for isoprenaline as well as calcium were studied in guinea pig papillary muscles. NICO could decrease the amplitude of contraction of papillary muscles dose-dependently. Propranolol and NICO might antagonize the inotropic effect of isoprenallne. Verapamil & NICO induced Ca2+ antagonistic effects in a non-competitive manner, & the maximal Ca2+ response of papillary muscles decreased signifi- cantly. The automaticity of papillary muscles was decreased Significantly when the concentration of NICO reached 1.4 mmol/L, but exerted no effect on their excitability & the functional refractory period.

THE EXPERIMENTAL ANTI-ARRHYTHMIC EFFECTS OF l-STEPHOLIDINE / 中国药理学通报

Intravenous injection of SPD 10 mg/kg could increase the tolerant dose of ouabain, and prevent the arrhythmias induced by acute myo-cardial ischemia in rats and that elicited by adrenaline-chloroform model in rabbits. SPD 60 mg/kg intraperitoneally could abolish the ventricular fibrillation produced by chloroform inhalation in mice. It inhibited the contractility, prolonged the functional refractory period and decreased the automaticity significantly of the isolated guinea pig papillary muscles, but no significant effect on excitability.

Mechanism of 5-hydroxytryptamine induced calcium signaling in cultured rat stomach fundus smooth muscle cells / 中国药理学通报

AIM To get an insight into intracellular signaling steps, a very early step in the signaling cascade, the biphasic Ca 2+ elicited by 5 HT in rat stomach fundus smooth muscle cells was investigated. METHODS Cells were cultured and loaded with Fluo 3 AM. [Ca 2+ ] i was measured by fluorescent intensity (FI) in each cell with confocal microscopy. RESULTS The resting FI level of SFSMC was 264?15. Stimulation of SFSMCs by 5 HT produced an elevation of [Ca 2+ ] i; Depletion of external Ca 2+ by addition of EGTA led to a significant attenuation of [Ca 2+ ] i change induced by 5 HT; Pre treatment of SFSMCs with ryanodine (10 ?mol?L -1 , 5 min) in D Hanks, the effect of 5 HT was completely inhibited; The stimulation of SFSMCs by 5 HT was partly attenuated by miaserin(10 ?mol?L -1 ), however, L type Ca 2+ channel antagonist lacidipine and G protein inhibitor NEM completely abolished the increase of [Ca 2+ ] i mediated by 5 HT; 5 HT mediated Ca 2+ release was reduced by phospholipase C specific inhibitor compound 48/80(1 2 ?g?ml -1 ); When protein kinase C was activated by phorbol 12 myristate 13 acetate (PMA 0 1 ?mol?L -1 , 5 min) the effect of 5 HT was inhibited, and the inhibitory effect of PMA was reversed by D sphingosine, a PKC inhibitor. CONCLUSION Our data suggest that G protein coupled 5 HT 2B receptor in the rat stomach fundus modulates 5 HT stimulated Ca 2+ increase, and it is coupled to calcium influx through L type calcium channels, and also intracellular calcium release by the opening of ryanodine receptor. The 5 HT 2B receptor mediated signal of 5 HT is transduced by PLC and PKC.

TOXIC EFFECT OF LIDOCAINE ON THE ACUTE ISCHEMIC HEART OF RABBIT AND THE ANTAGONISTIC ACTION OF L-4-THIAZOLIDINE CARBOXYLIC ACID / 解放军医学杂志

This paper reported that lidocaine given intravenously 5mg/kg 9 min before occlusion of left ventricular coronary artery (CO) may shorten the latent period for ventricular arrhythmias from 6.2?1.9 min to 3.7?0.9 min (P