Performing multiple tests without adjusting the test level results in a higher-than-intended overall familywise error rate(FWER).This phenomenon is known as the multiplicity problem.In this paper,we first introduced the mechanism of multiplicity problem based on the classification and characterization of clinical endpoints.Then,strategies and methods to solve the multiplicity problem were introduced,including the parallel strategy/single-step method,the sequential strategy/multistep method/stepwise method,and their combinations.The results of different analytic strategies may vary.The practical application of the above common strategies and statistical methods were introduced through the case studies of domestic and foreign investigator initiated clinical trial.Multiplicity adjustment for multiple endpoints in clinical trials can be achieved by a single strategy or a combination of strategies.Depending on the selected strategy or combination,the statistical methods and significance level(denoted as α)for each test hypothesis are determined to effectively control the multiplicity problem.

Performing multiple tests without adjusting the test level results in a higher-than-intended overall familywise error rate(FWER).This phenomenon is known as the multiplicity problem.In this paper,we first introduced the mechanism of multiplicity problem based on the classification and characterization of clinical endpoints.Then,strategies and methods to solve the multiplicity problem were introduced,including the parallel strategy/single-step method,the sequential strategy/multistep method/stepwise method,and their combinations.The results of different analytic strategies may vary.The practical application of the above common strategies and statistical methods were introduced through the case studies of domestic and foreign investigator initiated clinical trial.Multiplicity adjustment for multiple endpoints in clinical trials can be achieved by a single strategy or a combination of strategies.Depending on the selected strategy or combination,the statistical methods and significance level(denoted as α)for each test hypothesis are determined to effectively control the multiplicity problem.

Objective? To compare the effect of European Nutritional Risk Screening (NRS 2002) and Patient General Subjective Score (PG-SGA) in perioperative patients with head and neck squamous cell carcinoma, and to provide evidence for clinical nutritional screening in perioperative patients with head and neck squamous cell carcinoma. Methods? Using convenience sampling method, 82 patients with head and neck squamous cell carcinoma who were admitted to the Department of Head and Neck Surgery of Zhejiang Cancer Hospital from October 2015 to December 2017 during perioperative period were selected as the study subjects. NRS 2002 and PG-SGA were used to longitudinally evaluate their nutritional status at admission, 1 day before operation, 2 days after operation, 1 week after operation and at discharge, respectively. The differences of nutritional status between the two assessment tools during perioperative period were compared. Results? The trend of malnutrition risk in NRS 2002 was similar to that in PG-SAG dynamic assessment from admission to discharge, all of which were in the form of "V". The positive rate of malnutrition in PG-SAG assessment was higher than that in NRS 2002, and the difference was statistically significant (P＜ 0.01). Conclusions? NRS 2002 and PG-SGA are both suitable for nutritional risk screening of head and neck squamous cell carcinoma patients, but the positive rate of PG-SGA is higher, which can effectively screen and evaluate the nutritional status of head and neck squamous cell carcinoma patients, and is conducive to timely providing nutritional intervention and treatment for patients.

Objective To investigate does intracellular protein degradation pathway play an important role in decrease of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs).MethodsTo establish a primary HUVECs culture methods,the HUVECs were incubated with concentration gradient group of TNF-α(0.01,0.1,1 and 10 ng/mL) in different time periods (24,48 and 72 h).The HUVECs were pretreated with NH4Cl or treated with caspase inhibitor or MG-132 1.5 h prior to incubation for an additional 24 h with TNF-α.The expression of eNOS was detected via Western blot assay.Results Treatment of the HUVECs with TNF-α(0.01-10 ng/mL) led to a dose-dependent reduction of eNOS expression.And treatment with TNF-α(1 ng/mL) reduced the eNOS expression in a time-depended manner.Compared with the TNF-α group,the protein expression level of eNOS was obviously increased in the co-working group of MG-123 and TNF-α.Conclusions TNF-α induces degradation of eNOS through a ubiquitin-proteasome pathway.

OBJECTIVES: The Tinnitus Handicap Inventory (THI) is a commonly used self-reporting tinnitus questionnaire. We undertook this study to determine the reliability and validity of the Chinese-Mandarin version of the Tinnitus Handicap Inventory (THI-CM) for measuring tinnitus-related handicaps. METHODS: We tested the test-retest reliability, internal reliability, and construct validity of the THI-CM. Two-hundred patients seeking treatment for primary or secondary tinnitus in Southwest China were asked to complete THI-CM prior to clinical evaluation. Patients were evaluated by a clinician using standard methods, and 40 patients were asked to complete THI-CM a second time 14+/-3 days after the initial interview. RESULTS: The test-retest reliability of THI-CM was high (Pearson correlation, 0.98), as was the internal reliability (Cronbach's alpha, 0.93). Factor analysis indicated that THI-CM has a unifactorial structure. CONCLUSION: The THI-CM version is reliable. The total score in THI-CM can be used to measure tinnitus-related handicaps in Mandarin-speaking populations.
Asian Continental Ancestry Group ; China ; Humans ; Reproducibility of Results ; Tinnitus ; Surveys and Questionnaires

Objective To improve the recognition of various CT appearances of hepatoblastoma(HB) and evaluate the role of CT in diagnosis. Method In a total of 24 cases, abdominal scan was performed. In 12 of them contrast enhanced CT was available. The CT manifestions of the 24 HB cases were retrospectively analyzed and correlated with clinical pathological findings. Results Fourteen tumors involved the right lobe, 4 tumors involved the left lobe,and 6 both liver lobes. One case invaded the liver diffusely.Most of HB appeared as an intrahepatic well circumscribed round or lobulated solid mass with or without pseudocapsule.Three of them manifested as multiple nodules and distributed in one or both liver lobes.Exophytic growing of tumor was seen in 7 cases. The tumor mass usually exhibited inhomogeneous density and heterogeneous enhancement,some associated with reticular and curvilinear density.Peripheral rim enhancement was present in 3 cases.Calcified foci were found in 6 cases.The hepatic parenchyma outside the tumor was normal in all cases.Two subdiaphragmatic and greater omentum tumor infiltrations could not be found on CT scan. Rare findings included tumor thrombus in one case in IVC, lymphnode metastasis in one case. Conclusion The various CT patterns described in this study are helpful in recognizing and evaluating the prognosis of HB.CT scan could acurately localize and characterize the mass,while not always correct in tumor staging.