RESUMO
Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
Assuntos
Fármacos Gastrointestinais , Neoplasias Gastrointestinais , China , Fármacos Gastrointestinais/uso terapêutico , Humanos , Preparações Farmacêuticas , Estados Unidos , United States Food and Drug AdministrationRESUMO
The objective of this study was to investigate early postoperative inflammatory small bowel obstruction (EPISBO) by applying gastrointestinal decompression to relieve abdominal distension. Thirty-six cases of patients were randomly divided into two groups: a control group (20 cases) and an observation group (16 cases). Routine continuous gastrointestinal decompression was assigned to the control group, while gastrointestinal decompression with dynamic and profound adjustment of the gastric tube and abdomen movement was assigned to the observation group, to induce abundant gastric juice and gas, and significantly relieve abdominal distension. A test was performed for each of the two groups to observe the relief time of the abdominal distension and the difference of abdominal girth of 5 cm before and after gastrointestinal decompression. Compared with the control group, the patients in the observation group with abdominal distension had earlier pain relief. More patients in the observation group had a difference of abdominal girth of 5 cm before and after gastrointestinal decompression. In gastrointestinal decompression, the method of dynamic and profound adjustment of the gastric tube and abdomen movement improve the effect of the gastrointestinal decompression, which relieves abdominal distention and promotes the postoperative recovery of organ functions.
Assuntos
Descompressão/métodos , Obstrução Intestinal/terapia , Intubação Gastrointestinal , Massagem , Complicações Pós-Operatórias/terapia , Abdome , Antropometria , Criança , Pré-Escolar , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Lactente , Masculino , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/terapiaRESUMO
Work-related musculoskeletal disorders (MSDs) are most commonly seen in all the occupational non-fatal injuries and illnesses for workers, especially those who are involved in labor-intensive industries. Participatory ergonomics is frequently used to prevent musculoskeletal disorders. This paper gives an overview of a historical perspective on the use of participatory ergonomics approach in reducing the health effects of labor-intensive industries. Progress, barriers and facilitators on the organization, implementation and evaluation of participatory ergonomics programs are studied. Participatory ergonomics seems a successful method to develop, prioritize measures to prevent MSDs. Participatory ergonomics can help industries reduce musculoskeletal injuries and disorders, improve workplace condition and promote health conditions of the workers.
Assuntos
Ergonomia , Doenças Musculoesqueléticas/prevenção & controle , Doenças Profissionais/prevenção & controle , Local de Trabalho , Humanos , Modelos TeóricosRESUMO
OBJECTIVE: The aim of this study is to investigate the effect of low-nitrogen and low-calorie parenteral nutrition (PN) combined with enteral nutrition (EN) on the inflammatory cytokines and immune function in patients with gastric cancer. PATIENTS AND METHODS: Between May 2012 and May 2014, 90 patients undergoing surgery for gastric cancer in our institution were involved in this double blind placebo study and randomly divided into experimental group and control group, 45 patients of each group. Patients in the control group would receive total parenteral nutrition (TPN) whereas patients in the experimental group would be supported with low-nitrogen and low-calorie PN combined with EN. RESULTS: On the 7th postoperative day 7, levels of IgA, IgM and IgG in experimental group were significantly higher than those in the control group and preoperative values (p < 0.05). CRP level was significantly lower than that of controls and preoperatively (p < 0.05). Levels of IL-2 and TNF-α were significantly higher than those of controls and preoperatively (p < 0.05). CONCLUSIONS: As low-nitrogen and low-calorie PN combined with EN can effectively improve the immune function, reduce the inflammatory reactions and improve the postoperative quality of life (QoL) and prognosis in patients with gastric cancer, it is suitable for clinical application.
Assuntos
Restrição Calórica , Citocinas/imunologia , Nutrição Enteral , Nitrogênio/administração & dosagem , Nutrição Parenteral , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/terapia , Adulto , Idoso , Biomarcadores/sangue , Restrição Calórica/métodos , Terapia Combinada/métodos , Citocinas/sangue , Método Duplo-Cego , Nutrição Enteral/métodos , Feminino , Seguimentos , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral/métodos , Neoplasias Gástricas/sangue , Resultado do TratamentoRESUMO
An electrolytic Zr(OH)4 gel has been coated on ASTM F-75 Co-Cr-Mo alloy specimens in 0.0625 M ZrO(NO3)2 solution with pH = 2.2 at a current density of 2 mA/cm2. After annealing at 623-973 K for 120 min in air, the ZrO2-coated specimen was evaluated by electrochemical polarization in Hank's solution, wear tests with UHMWPE (Ultra-high molecular-weight polyethylene) under a load stress of 50 MPa, scratch tests, surface morphology observations, and XRD analysis. The ZrO2-coated specimen annealed at 773 K for 120 min revealed a good adhesion of 610 MPa on Co-Cr-Mo substrate, a lower wear loss of UHMWPE and a higher protection potential than the uncoated specimen in Hank's solution. A monoclinic structure with (1 1 1) preferred orientation parallel to the sheet plane was detected at 623 K < or = T < or = 673 K and a tetragonal structure of ZrO2 was detected at T > or = 773 K. Then a monoclinic structure with random orientation and a tetragonal structure were mixed at T > or = 973 K.
Assuntos
Materiais Revestidos Biocompatíveis , Prótese de Quadril , Zircônio , Ligas , Cromo , Cobalto , Eletrólise/métodos , Géis , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , MolibdênioRESUMO
We have synthesised and examined the enzymatic incorporation properties of the 5'-triphosphates of 2'-deoxyribosyl pyrrole 3-monocarboxamide (dMTP) and 2'-deoxyribosyl pyrrole 3,4-dicarboxamide (dDTP). These analogues we had hoped would behave as ambivalent base analogues in that they can present two alternative hydrogen-bonding faces either by rotation about the carboxamide group or about the glycosidic bond. The two pyrrole derivatives, dMTP and dDTP, exhibit a preference for incorporation with Klenow polymerase. They are preferentially incorporated as either A or C.
Assuntos
DNA Polimerase Dirigida por DNA/química , Nucleotídeos/química , Nucleotídeos/síntese química , Pirróis/química , Sequência de Bases , Cristalografia por Raios X , Conformação de Ácido Nucleico , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
OBJECTIVE: To study the chemical constituents of processed green tangerine peel(Citrus reticulata). METHOD: Using chemical techniques and spectroscopic analysis. RESULT: Four compounds were isolated from the peel and identified as hesperidin, neohesperidin, nobiletin and tangeritin. CONCLUSION: The compounds were obtained from this peel for the first time.
Assuntos
Citrus/química , Flavonas , Hesperidina/isolamento & purificação , Plantas Medicinais/química , Ácido Acético , Flavonoides/química , Flavonoides/isolamento & purificação , Frutas/química , Hesperidina/química , Temperatura Alta , Tecnologia FarmacêuticaRESUMO
The feasibility of using beta,beta'-monochloromethylene diadenosine 5',5"'-P1,P4-tetraphosphate (AppCHCl-ppA) as an antithrombotic agent was studied in a rabbit intracarotid cannula thrombosis model previously shown to be sensitive to antiplatelet agents. This analogue, having a P-C-P bridge in place of a P-O-P internucleoside linkage, has been found resistant to phosphodiesterase activity. Rabbits were infused with the dinucleotide at a dose of 50 mg per kg over a 2-hr period, at a controlled rate by pump. A 1-cm length of polyethylene cannula (1 mm i.d.) was tied into the carotid artery. Animals were stable under general anesthesia during the entire period of the experiment. In the control group, 16 of 20 animals formed clots, an incidence of 80%, whereas in the test animals, 6 of the 20 formed clots (30% incidence, P < 0.05). After preincubation of whole blood with 50 microM AppCHClppA at 37 degrees C for up to 3 hr, a consistent suppression of ADP-induced platelet aggregation was observed. The present study suggests that AppCHClppA may be useful as an antithrombotic agent in certain clinical situations, such as hemodialysis, arteriovenous shunts, and introduction of artificial heart valves. It may also possibly prevent extension of recent clots. The toxicity and metabolism of AppCHClppA have, however, yet to be explored.
Assuntos
Plaquetas/fisiologia , Fosfatos de Dinucleosídeos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Trombina/antagonistas & inibidores , Animais , Tempo de Sangramento , Plaquetas/efeitos dos fármacos , Cinética , Masculino , CoelhosRESUMO
Enzymes which cleave P-O bonds can be blocked by phosphonate analogues of biological phosphates. alpha-Fluorophosphonates are more electronegative at the bridging carbon than simple methylenephosphonates which improves their use for the study of enzymes. Thus, the beta,gamma-difluoromethylene analogue of ATP is a viable substrate for (2----5)An synthetase which converts it into (2----5)An species having a 5'-beta,gamma-difluoromethylene-trisphosphate. This binds strongly to RNase L but does not activate it. The unsymmetrical Ap4Aases from Artemia and lupin are strongly inhibited by P2,P3-fluoromethylenebisphosphonate- and by P1,P4-dithiophosphate-analogues of diadenosyl-5',5"-P1,P4-tetraphosphate while anomalous, non-regiospecific cleavage of some P2,P3-bridged mimics is observed. Certain such analogues inhibit both platelet aggregation in vitro and arterial blood-clotting in rabbits. Separation of the diastereo-isomers of P1,P4-dithiophosphate analogues of Ap4A is achieved using reverse-phase hplc which provides direct access to beta,gamma-CHF-bridged analogues of ATP with resolved stereochemistry at the CHF centre.
Assuntos
Enzimas/metabolismo , Nucleotídeos/química , Organofosfonatos/química , Fosfatos/química , Trifosfato de Adenosina/análogos & derivados , Estrutura MolecularRESUMO
To investigate the influence of the pyrimidine 2-keto group on selection of nucleotides for incorporation into DNA by polymerases, we have prepared two C nucleoside triphosphates that are analogues of dCTP and dTTP, namely 2-amino-5-(2'-deoxy-beta-d-ribofuranosyl)pyridine-5'-triphosphate (d*CTP) and 5-(2'-deoxy- beta-d-ribofuranosyl)-3-methyl-2-pyridone-5'-triphosphate (d*TTP) respectively. Both proved strongly inhibitory to PCR catalysed by Taq polymerase; d*TTP rather more so than d*CTP. In primer extension experiments conducted with either Taq polymerase or the Klenow fragment of Escherichia coli DNA polymerase I, both nucleotides failed to substitute for their natural pyrimidine counterparts. Neither derivative was incorporated as a chain terminator. Their capacity to inhibit DNA polymerase activity may well result from incompatibility with the correctly folded form of the polymerase enzyme needed to stabilize the transition state and catalyse phosphodiester bond formation.
Assuntos
Desoxirribonucleotídeos/síntese química , Inibidores da Síntese de Ácido Nucleico , Piridinas/síntese química , Piridonas/síntese química , Nucleotídeos de Pirimidina/síntese química , Sequência de Bases , DNA Polimerase I/antagonistas & inibidores , Primers do DNA , Nucleotídeos de Desoxicitosina , Desoxirribonucleotídeos/química , Desoxirribonucleotídeos/farmacologia , Escherichia coli/enzimologia , Indicadores e Reagentes , Estrutura Molecular , Reação em Cadeia da Polimerase , Piridinas/química , Piridinas/farmacologia , Piridonas/química , Piridonas/farmacologia , Nucleotídeos de Pirimidina/química , Nucleotídeos de Pirimidina/farmacologia , Relação Estrutura-Atividade , Taq Polimerase/antagonistas & inibidores , Nucleotídeos de TiminaRESUMO
The model equations of the growth phase of rHSA fermentation were derived on the base of both elemental balance and metabolic balance. The unknown parameters of the model were estimated by multivariable optimization. The model can preferably describe the relations between different macroscopic reaction rates of the process and provide the key for the high-density cultivation of Pichia pastoris.
Assuntos
Fermentação , Pichia/metabolismo , Albumina Sérica/metabolismo , Pichia/crescimento & desenvolvimento , Proteínas Recombinantes/metabolismoRESUMO
We have previously demonstrated in a series of searches for antithrombotic agents that diadenosine 5',5"'-P1,P4-tetraphosphate (AppppA) and its analogues are competitive inhibitors of ADP-induced platelet aggregation. Among various analogues, the P2,P3-monochloromethylene analog of AppppA (AppCHClppA) is superior to unmodified AppppA in its antiplatelet and antithrombotic effects. In this communication, we compare the antiplatelet potency of five newly synthesized agents with that of AppCHClppA. The five new agents include four diadenosine polyphosphate analogues [Ap(s)pCHClpp(s)A (p(s) indicates a thiophosphate), dAppCHClppdA, dAp,pCHClpp(s)dA, and AppCHClpCHClppA], and an adenosine tetraphosphate analogue (AppCHClpCHClp). When tested for their inhibitory effects on platelet aggregation by ADP, the most promising agent among them was Ap(s)pCHClpp(s)A. Both molecular and functional integrity of this compound proved to be stable in blood at 37 degrees C for at least 3 h. It also showed an excellent heat stability. This agent inhibits a number of aspects of ADP-induced platelet activation-e.g., release reaction, cytoplasmic calcium mobilization, thromboxane production, fibrinogen binding sites, and platelet factor 3 activity. Moreover, platelet aggregation induced by agonists other than ADP-e.g., arachidonic acid, collagen, and epinephrine-was inhibited partially by Ap(s)pCHClpp(s)A. It is concluded that (i) Ap(s)pCHClpp(s)A is a promising antiplatelet agent; (ii) it is resistant to blood phosphodiesterases and stable to heat treatment; (iii) platelet aggregation induced by collagen, epinephrine, or arachidonic acid is also inhibited in part by this agent; and (iv) specificity of the inhibitory effects is presented by unmodified adenosine moieties of the agent. Resistance to phosphodiesterases raises the possibility of oral administration.
Assuntos
Plaquetas/efeitos dos fármacos , Fosfatos de Dinucleosídeos/farmacologia , Inibidores da Agregação Plaquetária/isolamento & purificação , Agregação Plaquetária/efeitos dos fármacos , Fosfatos de Dinucleosídeos/química , Humanos , Inibidores da Agregação Plaquetária/farmacologiaRESUMO
The effects of cultural conditions, which were fermentation period when methanol was as sole carbon source, methanol concentration, range of pH, on the expression of the chimeric protein of Plasmodium falciparum in genetically engineered methylotrophic Pichia pastoris were investigated by shake flask experiments in this paper. The results showed: (1) fermentation period with methanol inducement is about 96 hours; (2) the optimum methanol concentration as sole carbon source is 10 g/L; (3) the range of pH is from 6.0 to 7.0. On the base of above experimental results the cell high-density fermentation had been done on the FMG-5L fermentor with multi-sensors. The results showed that the cell optical density (OD600) can reached 550 and the maximum expression level of target proteins was 780 mg/L which was 4 times higher or more than the shake flask culture's.
Assuntos
Fermentação , Pichia/metabolismo , Plasmodium falciparum/química , Proteínas Recombinantes de Fusão/biossíntese , Animais , Concentração de Íons de Hidrogênio , Metanol/farmacologia , Proteínas de Protozoários/biossínteseRESUMO
Permeabilized preparations of equine infectious anemia virus (EIAV) are shown here to support efficient and accurate synthesis of full-length double-stranded proviral DNA. When (-) and (+) strand products were analyzed by Southern blotting, a discontinuity, mapping approximately to the center of the EIAV genome, could be demonstrated for the (+) strand, predicting a second site for initiation of DNA synthesis and a specific mechanism of (+) strand termination. Precise localization of this (+) strand origin within the integrase (IN) coding region was achieved through its in vitro selection and extension into, and excision from, nascent DNA by purified recombinant p66/p51 EIAV reverse transcriptase (RT), suggesting that the EIAV genome harbors a central polypurine tract (cPPT). In addition, a model system was developed for evaluating whether sequences immediately downstream of the cPPT would terminate (+) strand synthesis in the context of strand displacement. Such a sequence was indeed discovered which functions in a manner analogous to that of the central termination sequence (CTS) of HIV, where A-tract-induced minor groove compression has been suggested to induce localized distortion of the nucleic acid duplex and termination of (+) strand synthesis. This interpretation is reinforced by experiments indicating that read-through of the CTS can be efficiently promoted by substituting 2,6-diaminopurine for adenine, thereby relieving minor groove compression. The nucleotide substitution can also shift the site of termination in strand displacement (+) strand synthesis. Collectively, our data support proposals that lentiviruses may have evolved specialized mechanisms for initiating and terminating (+) strand DNA synthesis at the center of their genomes.