With the development of the research on biotechnology and modern pharmacy, the application of enzyme drugs have grown rapidly and enzyme drugs have become an important branch of biopharmaceutics. In this article, some new varieties of therapeutic enzymes, enzyme targets, mechanisms and new technologies of application in therapeutic enzymes were reviewed, and the direction of development of therapeutic enzymes were discussed.
Adenosine Deaminase ; genetics ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Enzyme Replacement Therapy ; methods ; Fibrinolytic Agents ; therapeutic use ; Protein C ; genetics ; therapeutic use ; RNA, Catalytic ; genetics ; therapeutic use ; Streptokinase ; genetics ; therapeutic use ; Urokinase-Type Plasminogen Activator ; genetics ; therapeutic use

OBJECTIVES: To study the association between infliximab trough level (IFX-TL) prior to maintenance treatment and disease outcome in children with Crohn's disease (CD). METHODS: A retrospective analysis was performed on 35 children with CD who received induction therapy with infliximab (IFX) and the measurement of IFX-TL before maintenance treatment from August 2018 to November 2021. Clinical data and laboratory markers at baseline and before maintenance treatment were collected, and the association between outcome and IFX-TL was analyzed. RESULTS: The clinical remission group, endoscopic remission group, and combined remission group had a significantly higher IFX-TL level than the corresponding non-remission groups (P<0.05), and there was no significant difference in the IFX-TL level between the biological remission and non-biological remission groups (P>0.05). The receiver operating characteristic (ROC) curve showed that IFX-TL had an area under the ROC curve of 0.959 (95%CI: 0.894-1) in predicting clinical remission, with a sensitivity of 90% and a specificity of 100% at the optimal cutoff value of 2.3 µg/mL (P<0.001). CONCLUSIONS Among children with CD receiving infliximab induction therapy, the children achieving clinical and endoscopic remission before maintenance treatment tend to have a higher level of IFX-TL. IFX-TL has a certain predictive value for clinical remission.
Child ; Humans ; Infliximab/therapeutic use* ; Crohn Disease/drug therapy* ; Gastrointestinal Agents/therapeutic use* ; Retrospective Studies ; C-Reactive Protein/analysis*

OBJECTIVETo compare the lipid lowering effects of Zhikang Granule (ZKG) and simvastatin.

METHODSForty-five out-patients with hyperlipemia who met the entry criteria were enrolled and randomized into two groups in the ratio of 2: 1, 30 patients in the ZKG group and 15 patients in the simvastatin group. The lipid lowering effects and safety of treatment during the 24-week therapeutic period, as well as the influence of treatment on plasma high sensitivity C reactive protein (hs-CRP) level in patients were observed.

RESULTSNo significant difference between the two groups was observed in serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) at the 4th, 8th, 12th and 24th week (P > 0.05). However, as compared with baseline, significant reduction of TC and LDL-C in both groups was shown at all the observing time points (P < 0.01), while the changes in TG and HDL-C were insignificant (P > 0.05). The control rates of LDL-C and TC in the ZKG group and the simvastatin group were 86.7% (26/30) versus 100% (15/15) at the 4th week, 80.0% (24/30) versus 100% (15/15) at the 8th week, 53.3% (16/30) versus 60.0% (9/15) at the 12th week, and 90.0% (27/30) versus 93.3% (14/15) at the 24th week, respectively, all showed insignificant difference between groups. No statistical differences were found between groups in levels of plasma transaminase, creatinine, uric acid and hs-CRP (P > 0.05).

CONCLUSIONZKG has a definite effect in lowering LDL-C and TC, and it is safe in long-term administration.

Aged ; C-Reactive Protein ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hyperlipidemias ; drug therapy ; Hypolipidemic Agents ; therapeutic use ; Lipids ; blood ; Male ; Middle Aged ; Phytotherapy ; Simvastatin ; therapeutic use

The functional mutation of c-kit and platelet-derived growth factor receptor α (PDGFRA) which encode proto-oncogene receptor tyrosine kinase are the crucial pathogeneses of gastrointestinal stromal tumors(GISTs). 80%-85% c-kit gene mutation including exon 11,exon 9,exon 13,exon 17 and 5%-10% PDGFRA gene mutation such as exon 18, exon 12 are examined in GISTs. Neither of c-kit or PDGFRA gene mutation are called wide type GISTs. The pathogeneses of wild type GISTs are not clear. The deficiency of succinate dehydrogenase B(SDHB)-related insulin-like growth factor 1(IGF-1R) activation, BRAF gene mutation and neurofibromatosis type 1 may be related to progression of wild type GISTs. More than half of metastatic GISTs patients receiving imatinib treatment can develop to c-kit secondary mutations, which are responsible for secondary resistance. However, the reasons of imatinib resistance in GISTs without c-kit secondary mutation need to be explored. At present, many clinical trials are ongoing to evaluate new drugs in GISTs treatment, including nilotinib, masitinib, pazopanib, dovitinib, ponatinib, dasatinib, crenolanib, linsitinib and immunotherapy, which may bring resistance GISTs treatment to new hope. Next generation sequencing (NGS) and liquid biopsy will be very important in GISTs research and clinical practice.
Benzimidazoles ; therapeutic use ; Exons ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Imatinib Mesylate ; Mutation ; Piperidines ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins c-kit ; genetics ; Pyrimidines ; therapeutic use ; Quinolones ; therapeutic use ; Succinate Dehydrogenase ; genetics ; Sulfonamides

OBJECTIVETo investigate the effect of plasma homocysteic acid (HCA) reduction on serum C-reactive protein (CRP) level in children with Kawasaki disease (KD).

METHODSSeventy-six children with KD were divided into 2 equal groups for treatment with aspirin and IVIG, or with vitamin B6 and folic acid besides in addition to aspirin and IVIG. Serum CRP level was tested before and after the treatments, and plasma HCA level was also measured after the treatments.

RESULTSSerum CRP level was comparable between the two groups before the treatment, but significantly reduced after vitamin B6 and folic acid treatment (7.56-/+2.94 mg/L vs 12.23-/+4.16 mg/L, P<0.05). Additional vitamin B6 and folic acid treatment significantly lowered plasma HCA level (4.56-/+1.14 micromol/L vs 7.79-/+1.79 micromol/L, P<0.05), and correlation analysis demonstrated a positive correlation between plasma HCA and serum CRP levels (r=0.697, P<0.01).

CONCLUSIONLowering plasma HCA can decrease serum CRP in children with KD to enhance the therapeutic effect.

Aspirin ; therapeutic use ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Female ; Folic Acid ; therapeutic use ; Homocysteine ; analogs & derivatives ; blood ; Humans ; Immunoglobulins, Intravenous ; therapeutic use ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; drug therapy ; Vitamin B 6 ; therapeutic use

OBJECTIVETo analyze the clinical manifestations and intervention against fulminant scrub typhus-associated hemophagocytic syndrome.

METHODThe medical records for the onset time of hemophagocytic syndrome, the clinical course, the chest radiographic findings, laboratory data, antibiotic therapy, clinical outcome and its prognosis were retrospectively reviewed.

RESULT(1) Four patients were diagnosed as scrub typhus based on clinical manifestations only, while 15 patients met the criteria of laboratory diagnosis. All 19 patients with scrub typhus had hemophagocytic syndrome. Eschar lesion was identified in 12 patients, 7 patients were described as an ulcer. A seasonal pattern (78.9% from June through September in 15 patients) was observed. Clinical misdiagnosis was common (all 19 cases). There were 9 patients with admitting diagnosis of scrub typhus, 10 patients were not diagnosed as scrub typhus after admission. In 5 cases within 3 days after admission diagnosis was corrected as scrub typhus. Until discharge from the hospital, 5 cases were not diagnosed with scrub typhus. In this study, the length of time from the illness onset (beginning of fever) to the occurrence of clinical symptoms was (9 ± 4) days. (2) All 19 patients had changed AST levels (149 ± 37) U/L, albumin levels (23 ± 4) g/L, C-reactive protein levels (103 ± 51) mg/L, and platelet count (48 ± 41) × 10⁹/L; bone marrow aspiration revealed in 16 patients marked hemophagocytosis. Weil-Felix agglutination test revealed positive results in 6 of 15 cases. Diagnostic IFA results were positive for 14 patients; 19 patients had interstitial pneumonitis and 17 patients had pleural effusion. (3) Five cases with failure to diagnose the disease had ineffective antibiotics treatment (imipenem or β-lactam-based regimens). These patients did not receive appropriate treatment with antibiotics against scrub typhus. Fourteen patients with admitting diagnosis of scrub typhus were successfully treated with appropriate antibiotics, 8 cases with chloramphenicol, 3 cases with azithromycin, and in 3 patients (2 cases of azithromycin and one case of erythromycin), therapy was then switched to chloramphenicol. Four patients were treated with methylprednisolone and 10 patients with dexamethasone. (4) During their hospitalization, the clinical course in five cases with failure to diagnose the disease rapidly developed and progressed to the life-threatening MODS, four of five cases died. However, the course in 14 patients were relieved and did not progress to MODS.

CONCLUSIONThe diagnosis of scrub typhus was frequently delayed, the early course of scrub typhus could be associated with hemophagocytic syndrome. Serious complications of MODS generally occur without antibiotic treatment. Scrub typhus-associated hemophagocytic syndrome should be taken into consideration among patients with acute systemic febrile illness, significant increases in levels of CRP, hypoalbuminemia, thrombocytopenia, splenomegaly, pneumonitis with pleural effusion, especially those with suspected exposure history. It was not easily recognized without careful observation and was present for a few days in each patient.

Anti-Bacterial Agents ; therapeutic use ; Azithromycin ; therapeutic use ; C-Reactive Protein ; analysis ; Clinical Laboratory Techniques ; Diagnosis, Differential ; Erythromycin ; therapeutic use ; Humans ; Imipenem ; therapeutic use ; Lymphohistiocytosis, Hemophagocytic ; epidemiology ; Pneumonia ; Retrospective Studies ; Scrub Typhus ; diagnosis ; drug therapy ; epidemiology

OBJECTIVETo investigate the effect of a tight control of blood glucose by intensive insulin therapy on human sepsis, and to explore the potential mechanism of the intensive insulin therapy.

METHODSEligible patients were randomized by a blinded pharmacist to receive tight control of blood glucose by intensive insulin therapy (maintenance of blood glucose at a level between 4.4 and 6.1 mmol/L) or to receive conventional treatment (maintenance of glucose at a level between 10.0 and 11.1 mmol/L). The expression of HLA-DR on peripheral monocytes was measured in 54 patients by flow cytometry on 24 h, 3 d, 5 d, 7 d, 10 d and 14 d of intensive care in parallel with serum c-reactive protein (CRP), severity of the disease (APACHE II score, SOFA score) and clinical data collection.

RESULTSPatients receiving intensive insulin therapy were less likely to require prolonged mechanical ventilation. Tight control of blood glucose significantly reduced the number of days during which leukopenia or leukocytosis and the days with hypo- or hyperthermia (P < 0.05). Hypoglycemia occurred in 3 patients (10.7%) in the tight control of blood glucose group. There were no instance of hemodynamic deterioration or convulsions. Compared with the conventional treatment, tight control of blood glucose also increased the HLA-DR expression of peripheral monocytes, and there were significantly difference on 3 d, 5 d and 7 d (P < 0.05). Whereas it suppressed the elevated serum CRP concentrations, there was significantly difference on 7 d (P < 0.05).

CONCLUSIONSTight control of blood glucose by intensive insulin therapy expedited healing of human sepsis, and increased the HLA-DR expression of peripheral and suppressed the elevated serum CRP. So, it is necessary to use insulin to strict control the glucose levels in human sepsis.

Blood Glucose ; metabolism ; C-Reactive Protein ; metabolism ; HLA-DR Antigens ; biosynthesis ; Humans ; Hyperglycemia ; drug therapy ; etiology ; metabolism ; Hypoglycemic Agents ; therapeutic use ; Insulin ; therapeutic use ; Sepsis ; complications

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(C_min) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole C_min were analyzed, and the changes of voriconazole C_min after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole C_min and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole C_min was negatively correlated with albumin level (r=-2.673). Voriconazole C_min in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole C_min showed that compared with voriconazole C_min 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole C_min> 5.0 mg/L group was increased (χ²=4.318, P=0.038). CONCLUSION The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole C_min, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole C_min of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Humans ; Male ; Female ; Voriconazole/therapeutic use* ; Antifungal Agents/therapeutic use* ; C-Reactive Protein ; Creatinine ; Glucocorticoids ; Retrospective Studies ; Drug Monitoring ; Hematologic Diseases

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the GI tract. Aberrant activation of tyrosine kinase through mutated KIT or platelet-derived growth factor receptor (PDGFRA) is the key pathogenic factor in most cases. Tyrosine kinase inhibitors (TKI) such as imatinib and sunitinib can suppress activation of tyrosine kinase receptor and has gained wide recognition as the first-line adjuvant therapy for advanced or high-risk GIST after surgery. It has become the classic model of treatment for solid tumor with molecular targeted therapy. However, the emergence of drug-resistance limits the long-term benefit of these drugs in most patients and has been a challenging clinical concern. Many factors are related to the resistance of TKI, of which KIT/PDGFRA mutation is the most important one. Genetic amplification of KIT, loss of heterozygosity, activation of an alternative downstream signaling pathways, and drug concentration are all possible factors. Therefore, reasonable individual treatment strategy and early resistance evaluation for imatinib- and sunitinib-resistant GISTs are important to patients with drug resistance in order to improve therapeutic efficacy and quality of life.
Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Drug Resistance, Neoplasm ; genetics ; Gastrointestinal Neoplasms ; drug therapy ; genetics ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; Humans ; Imatinib Mesylate ; Indoles ; therapeutic use ; Mutation ; Piperazines ; therapeutic use ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins c-kit ; genetics ; Pyrimidines ; therapeutic use ; Pyrroles ; therapeutic use ; Receptor, Platelet-Derived Growth Factor alpha ; genetics

OBJECTIVETo evaluate the clinical efficacy and safety of Qiangji Recipe (QR) in ad- junctive treatment of axial undifferentiated spondyloarthritis (axuSpA) through a four-week open study.

METHODSFifty-four axuSpA patients of Shen-deficiency Du-channel cold syndrome (SDDCS) in line with inclusive criteria were recruited and assigned to the treatment group and the control group according to random digit table, 27 in each group. Patients in the control group took Celecoxib Capsule (0.2 g each time, twice per day). Patients in the treatment group additionally took QR (consisting of Herba Epimedii 15 g, antler glue 15 g, Cibotium Barometz 15 g, eucommia bark 20 g, dipsacus asper 10 g, two toothed achyranthes root 15 g, drynaria 15 g, Taxillus Chinensis 20 g, ground beetle 10 g, scorpion 5 g, wild celery 10 g, notopterygium incisium 10 g, cow-fat seed 10 g, white mustard seed 6 g, and licorice root 6 g, one dose per day, twice daily). The therapeutic course for all was 4 weeks. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), total body pain and spinal pain, patient and physician global assessment on a four-point scale, the Ankylosing Spondylitis Quality of Life (ASQoL), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured before and after 4 weeks of treatment. The primary end point in this study was the proportion of patients with a 20%improvement response accord- ing to the ASAS International Working Group Criteria (ASAS 20 responders) at week 4.

RESULTSTotally 50 patients completed this trial, 26 in the treatment group and 24 in the control group. Improvement of BASDAI, BASFI, BASMI, ASQoL, ESR, and CRP was shown in both groups after treatment. Better effect was shown in the treatment group in all indices except ESR and BASMI after treatment (P < 0.05, P < 0.01). Twenty cases (accounting for 76.92%) in the treatment group achieved ASAS 20 response at week 4, while 12 cases (accounting for 50.00%) in the control group achieved ASAS 20 response at week 4 (P < 0.05). No obvious adverse reaction occurred in the two groups.

CONCLUSIONQR combined Celecoxib Capsule showed better effect in treating axuSpA patients than using Celecoxib Capsule alone.

Blood Sedimentation ; C-Reactive Protein ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Pain ; Quality of Life ; Spondylitis, Ankylosing ; drug therapy