Zanubrutinib is a highly selective second-generation BTK inhibitor developed in China and first approved by the U.S. Food and Drug Administration (FDA) as a novel antineoplastic drug. In recent years, with the birth of molecularly targeted drugs, the treatment of B-cell lymphoma have entered the era of targeted therapy, and immunotherapy has been widely accepted. Especially in some relapsed and refractory lymphomas, zanubrutinib has shown deep and sustained remissions and a favorable safety, which lays a foundation for precision therapy. In this review the clinical application and new progress for zanubrutinib in B-cell lymphoma was summarized briefly.
Humans ; Lymphoma, B-Cell/drug therapy* ; Piperidines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use*

Anemia, Aplastic/drug therapy* ; Benzoates/therapeutic use* ; Cyclosporine/therapeutic use* ; Humans ; Hydrazines/therapeutic use* ; Immunosuppressive Agents ; Pyrazoles/therapeutic use*

OBJECTIVETo evaluate the efficacy and safety of celecoxib in treating inflammatory(Type IIIA) chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS-IIIA type).

METHODSSixty-four patients with diagnosed CP/CPPS-IIIA were randomized equally into two groups, Group A treated with celecoxib 200 mg daily(qd), while Group B with 200 mg twice a day(bid), both for 6 weeks. The white blood cell (WBC) count in expressed prostate secretion(EPS) and National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI) were assessed and compared at baseline(0 week) and at 2, 4, 6 weeks or the endpoint.

RESULTSThe mean number of WBC in EPS and the mean NIH-CPSI total scores were decreased gradually after treatment from baseline in both groups. The mean number of WBC of in EPS of either group at the endpoint was decreased by 46.2% and 69.4% respectively(Group A vs Group B) compared with the baseline level. The mean NIH-CPSI total scores of the two groups were decreased respectively by 5.6 and 8.3 points (Group A vs Group B). In terms of the above two parameters, Group B, responded better than Group A to the treatment. The differences observed above were statistically significant(all P < 0.05). No serious adverse event presented.

CONCLUSIONCelecoxib is effective and safe for patients with CP/CPPS(IIIA). The dosage of 200 mg twice a day is more efficacious than that of 200 mg daily.

Adult ; Celecoxib ; Chronic Disease ; Cyclooxygenase Inhibitors ; therapeutic use ; Humans ; Male ; Middle Aged ; Prostatitis ; drug therapy ; Pyrazoles ; Sulfonamides ; therapeutic use

Humans ; Leukemia, Myelomonocytic, Chronic/drug therapy* ; Nitriles ; Pyrazoles/therapeutic use* ; Pyrimidines

OBJECTIVETo examine the chemopreventive effect of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib for Barrett's esophagus in rats.

METHODSFifty 8-week-old male Sprague Dawley rats underwent esophagojejunostomy to induce Barrett's esophagus model. Four weeks after operation the animals were given celecoxib 10 mg/(kg*d(-1))(celecoxib group), or saline 1 ml (control group). Another 10 rats were sham operation group. All animals were sacrificed at 20 week after surgery. The degree of inflammation, Barrett's esophagus, adenocarcinoma, COX-2 expression and PGE(2) of animals were assessed.

RESULTAmong 60 rats, 6 rats died in celecoxib group, 8 rats died in control group, 1 rat died in sham operation group, and 45 (75%) rats completed the study. The incidence of mild, moderate and severe degree esophageal inflammation in celecoxib group and control group was 14/19(73.68%), 4/19(21.05%), 1/19(5.26%); 4/17(23.53%), 5/17(29.41%), 8/17(47.06%)(P<0.05), respectively. The incidence of Barrett's esophagus was 7/19(36.84%), 13/17(76.47%) in two group respectively(P<0.05); The incidence of Barrett's esophagus with dysplasia was 2/19(10.53%), 8/17(47.06%)(P<0.05), respectively. The expression of COX-2 was 1/7(14.29%), 10/13(76.92%)(P<0.05) in two groups. PGE2 content was significantly lower in the celecoxib group than that in control group(P<0.001). No esophageal pathological changes were found in sham operation group.

CONCLUSIONSelective COX-2 inhibitors celecoxib can inhibit inflammations, development of Barrett's esophagus and esophagus adenocarcinoma.

Animals ; Barrett Esophagus ; metabolism ; prevention & control ; Celecoxib ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Dinoprostone ; metabolism ; Male ; Pyrazoles ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; therapeutic use

Being a great threaten for human health, obesity has become a pandemic chronic disease. There have been several therapeutic treatments for this social health issue, including diet and exercise therapy, medication and surgery, among which the diet is still the most common way. However, none of these therapeutic measures available is ideal, making it necessary to find an effective medical treatment. The endocannabinoid system, which is well known for its contributions in certain mental processes such as relaxation, amelioration of pain and anxiety, and sedation initiation, has been recently reported to play an essential role in regulating appetite and metabolism to maintain energy balance, leading to the belief that endocannabinoid system is closely related to obesity. This new discovery deepens our understanding of obesity, and provides us with a new direction for clinical obesity treatment. Rimonabant is an antagonist for CB1, and has entered the market in some countries. However, although effective as an anti-obesity drug, rimonabant also causes obviously adverse side-effects, thus is being doubted and denied for medical usage.
Animals ; Anti-Obesity Agents ; therapeutic use ; Cannabinoid Receptor Modulators ; antagonists & inhibitors ; metabolism ; Endocannabinoids ; Humans ; Obesity ; drug therapy ; metabolism ; Piperidines ; therapeutic use ; Pyrazoles ; therapeutic use ; Receptors, Cannabinoid ; metabolism

Adenine/analogs & derivatives* ; Bridged Bicyclo Compounds, Heterocyclic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Piperidines ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use* ; Rituximab/therapeutic use* ; Sulfonamides

INTRODUCTIONDirect oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation.

MATERIALS AND METHODSLaboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations.

RESULTSProthrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing.

CONCLUSIONKnowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper.

Antithrombins ; therapeutic use ; Blood Coagulation Tests ; Dabigatran ; therapeutic use ; Factor Xa Inhibitors ; therapeutic use ; Humans ; Partial Thromboplastin Time ; Practice Guidelines as Topic ; Prothrombin Time ; Pyrazoles ; therapeutic use ; Pyridones ; therapeutic use ; Rivaroxaban ; therapeutic use ; Singapore

OBJEVTIVETo evaluate the therapeutic effects of different therapeutic regimens for non-small-cell lung cancer (NSCLC) with or without EML4-ALK rearrangement.

METHODSTwenty-one ALK-positive and 50 ALK-negative NSCLC patients who received voluntarily EML4-ALK testing and 75 NSCLC patients without AL testing were enrolled in this study. The 3 groups of patients received different treatments, and the therapeutic effects, progression-free survival (PFS), and treatment-related adverse events were analyzed.

RESULTSCrizotinib treatment obviously prolonged the PFS in EML4-ALK-positive patients with an objective response rate (OOR) of 61.9% and a median response duration of 16 months, which were significantly better than those in with ALK-negative patients and patients without ALK testing who received different second-line therapies.

CONCLUSIONCrizotinib is superior to platinum-based chemotherapy in NSCLC patients with ALK rearrangement. ALK rearrangement id not a modifier of the effect of chemotherapy regimens in NSCLC patients.

Carcinoma, Non-Small-Cell Lung ; drug therapy ; Disease-Free Survival ; Humans ; Lung Neoplasms ; drug therapy ; Oncogene Proteins, Fusion ; Pyrazoles ; administration & dosage ; therapeutic use ; Pyridines ; administration & dosage ; therapeutic use

OBJECTIVE: To evaluate the efficacy and safety of ruxolitinib in patients with polycythemia vera (PV). METHODS: The clinical data of patients with PV treated with ruxolitinib in Peking Union Medical College Hospital from January 1, 2013 to December 31, 2019 were retrospectively analyzed. The starting dose of oral ruxolitinib was 10 mg twice daily and could be increased after 3 months of treatment if hematocrit (HCT) control was not achieved. HCT control was defined as HCT<45% in the absence of phlebotomy. RESULTS: Thirty-three patients (17 males and 16 females) were treated with ruxolitinib at a median age of 50 (21-72) years. JAK2V617F and JAK2exon12 alleles were detected in 31 and 2 patients, respectively. Before treatment, median hemoglobin level was 187 (166-208) g/L, median white blood cell and platelet level was 10.4 (5.0-15.8)×10⁹/L and 457(237-677)×10⁹/L, respectively. Totally 17 patients (51.5%) who were resistant to or intolerant of hydroxyurea were treated with ruxolitinib as second-line therapy, and 16 patients (48.5%) were treated with ruxolitinib as first-line therapy voluntarily. The median time since PV diagnosis to treatment of ruxolitinib was 47 (3-188) months. By December 31, 2019, all the patients continued to receive ruxolitinib. The median duration of ruxolitinib exposure was 19 (2-91) months. Both in the first-line therapy group and second-line therapy group, 15 cases (accounting for 93.8% and 88.2%, respecitvely) achieved HCT control. The median time from start of therapy to HCT control was 2.2 (0.8-11.6) months. One patient (3.0%) had disease progression after HCT control. The most common hematologic adverse events included anemia and thrombocytopenia, according to CTCAE classification, including 1 case of grade 1 anemia (3.0%) and 1 case of grade 2 thrombocytopenia (3.0%). There was no thromboembolic event occurred during the therapy of ruxolitinib. CONCLUSION The remission rate of HCT in PV patients treated with ruxolitinib is high, and adverse reactions are rare. Ruxolitinib is effective in HCT control and generally well tolerated in patients with PV.
Adult ; Aged ; Anemia ; Female ; Hemoglobins/therapeutic use* ; Humans ; Hydroxyurea/therapeutic use* ; Male ; Middle Aged ; Nitriles ; Polycythemia Vera/drug therapy* ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Thrombocytopenia ; Young Adult