Clinical research is usually aimed at and guided by therapeutic efficacy. Clarifying the placebo effect and the nocebo effect from treatment outcomes is an important issue in clinical research. This paper reviews the meaning of the placebo effect， suggesting that factors that may produce the placebo effect in clinical practice include past experience associations， patient expectations， suggestion， and doctor-patient relationships. It also summarizes the characteristics of the nocebo effect， its influencing factors， and its impact on clinical prognosis. Combining the characteristics of traditional Chinese medicine， this paper explores the design of acupuncture clinical trials that can reflect the measurement of the placebo effect， attempting to provide a clearer interpretation of the placebo effect in the evaluation of acupuncture efficacy in traditional Chinese medicine. Taking primary insomnia as an example， a prospective randomized placebo-controlled trial is designed to observe and evaluate the relationship between the treatment effects of acupuncture and the placebo effect in different patients under the treatment of the same doctor. Group comparisons will help better distinguish clinical effects in different situations. The authors also attempt to explore the responsive population to the placebo effect and the effects of placebos in different populations.

ObjectiveTo construct the core outcome set （COS） for premature ovarian insufficiency （POI） treated with traditional chinese medicine （TCM）， thereby standardizing the effect evaluation system of POI clinical researches. MethodsDatabases including PubMed， EMbase， Cochrane Library， Web of Science， CNKI， Wanfang， VIP， SinoMed from January 2017 to December 31， 2021， and Chinese Clinical Trials Registry （ChiCTR）， ClinicalTrials.gov were searched to collect the outcomes used in clinical studies of POI. Supplemented with the patients preferred outcomes through semi-structured interviews， the outcome pool was then constructed. Finally through the Delphi survey and consensus conference， the COS for POI was obtained. ResultsA total of 554 clinical researches and 14 registered clinical research protocols were included. A semi-structured interview was conducted within 20 patients. A total of 77 outcomes were included in the pool after consolidation. After two rounds of Delphi surveys， 20 outcomes were initially included. The COS， which was finalized through expert consensus conference， consists of 8 outcomes in 3 domains， which were ovarian reserve function （follicle stimulating hormone， estradiol， anti-Mullerian hormone， sinus follicle count）， menstruation-related indicators （menstrual symptoms condition） and fertility indicators （pregnancy rate， live birth rate and the numbers of retrieved oocytes）. Through expert discussion， the corresponding measurement methods as well as the measurement time points of the COS were determined. ConclusionThis study formed COS for clinical studies of TCM in the treatment of POI， by practicing the general method of developing COS， and exploring the key points of developing COS with TCM features.

Objective:To discuss the quantitative evaluation of left ventricular systolic function in patients with light-chain amyloidosis (AL) by pressure-strain loop (PSL).Methods:Forty-six patients with clinically diagnosed as AL in the Affiliated Tumor Hospital of Zhengzhou University from January 2018 to December 2020 were selected as case group, and they were divided into 2 groups according to whether the thickness of interventricular septum and posterior wall at end-diastole was >12 mm; ①cardiac amyloidosis (CA) group (21 cases, the thickness>12mm); ②non cardiac amyloidosis (NCA) group (25 cases, the thickness≤12 mm). Twenty five healthy volunteers were selected as control group at the same time. Routine echocardiography was performed in all subjects.Two-dimensional dynamic images of the left ventricular apical two-chamber, three-chamber, and four-chamber views were collected for three consecutive cardiac cycles using two-dimensional speckle-tracking. A tracing analysis was conducted and blood pressure was entered on the off-line Echo PAC 203 software, and the left ventricular global longitudinal strain (GLS), peak strain time dispersion(PSD), global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were obtained. The differences of GLS, PSD and myocardial work (GWI, GCW, GWW, GWE) parameters were compared between groups, and Pearson correlation was used to analyze the correlations.Results:①Routine echocardiography: Compared with the control group and NCA group, inter-ventricular septum thickness (IVST), left ventricle posterior wall thickness (LVPWT), left ventricular mass index (LVMI), left atrial diameter (LAD), and E/e′ in CA group were increased, while left ventricular ejection fraction (LVEF) was decreased; ②Compared with the control group, GLS, GWI, and GCW in NCA group were decreased, while there were no statistically differences in GWE, PSD, and GWW between the two groups (all P>0.05); Compared with the control group and NCA group, GLS, GWI, GCW, and GWE were obviously decreased, while PSD and GWW were obviously increased in CA group.③ Correlation analysis showed that: the absolute value of GLS was positively correlated with GWI, GCW and GWE ( r=0.654, 0.695, 0.788; all P<0.001), and negatively correlated with GWW, and PSD ( r=-0.710, -0.625; all P<0.001). Besides, PSD had negative correlation with GWI, GCW and GWE ( r=-0.754, -0.653, -0.702; all P<0.001), and positive correlation with GWW ( r=0.676, P<0.001). Conclusions:PSL can quantitatively evaluate the left ventricular systolic function of AL patients, while the myocardial work parameters are conducive to evaluate the degree of cardiac involvement in the course of AL patients.

Objective:To investigate the mid-term clinical efficacy and imaging changes of Waveflex semi-rigid internal fixation system combined with posterior lumbar interbody fusion (PLIF) in the treatment of double segmental lumbar degenerative diseases.Methods:The data of 51 patients with lumbar degenerative diseases who underwent surgery from September 2014 to September 2015 were retrospectively analyzed, including 29 males and 22 females, aged 65.5±5.6 years (range 58-73 years). Preoperative intervertebral space degeneration grade by University of California at Los Angeles (UCLA) and Pfirrmann intervertebral disc degeneration grade were recorded. 23 cases of primary responsible segments were treated with decompression, fixation and fusion, and adjacent secondary responsible or degenerative segments were treated with Waveflex semi-rigid internal fixation (combined group); 28 cases of double segments were treated with decompression, fixation and fusion (fusion group). Disc height index (DHI) and intervertebral foramina height (IFH) of the semi-rigid fixation segments, DHI and IFH of the upper adjacent intervertebral space, and horizontal displacement of the upper adjacent vertebral body (HD) were measured on lateral X-ray films of lumbar spine; In the fusion group, DHI and IFH adjacent to the upper vertebral space and HD adjacent to the upper vertebral body were measured. The efficacy was evaluated by short-form McGill Pain Questionnaire (SF-MPQ) and Oswestry disability index (ODI).Results:51 cases were followed up for 5.4±0.3 years (range 5.2-6.3 years). The low back and leg pain and function in the combined group and fusion group were significantly improved compared with those before operation. SF-MPQ and ODI at 3 months, 1 year, 5 years after operation were significantly different from those before operation ( P<0.05). In the combined group, the DHI of semi-rigid internal fixation segments before operation and 3 months, 1 year, 5 years after operation were 37.8%±7.6%, 37.9%±7.4%, 36.5%±6.9% and 36.0%±7.1% respectively ( P>0.05); The IFH of semi-rigid internal fixation segments before operation and 3 months, 1 year, 5 years after operation were 21.5±2.8, 21.4±2.8, 20.4±2.7, 19.4±2.4 mm respectively ( P<0.05); The DHI of the upper segment adjacent to semi-rigid internal fixation before operation and 3 months, 1 year, 5 years after operation were 37.1%±9.3%, 36.8%±9.1%, 35.2%±9.1%, 33.9%±8.8% respectively ( P>0.05); The IFH of the upper segment adjacent to semi-rigid internal fixation before operation and 3 months, 1 year, 5 years after operation were 21.9±3.0, 21.4±3.0, 20.4±2.9, 19.5±2.7 mm, respectively ( P<0.05). The HD of upper vertebral body adjacent to semi-rigid internal fixation before operation and 3 months, 1 year, 5 years after operation were 2.2±0.7, 2.3±0.5, 2.5±0.5, 2.8±0.5 mm respectively ( P<0.05). At the last follow-up, one case of semi-rigid titanium rod fracture, one case of screw loosening at semi-rigid internal fixation segment, three cases with unsatisfied numbness relief, and 2 cases of facet joint spontaneous fusion at semi-rigid fixation segment occurred in the combined group. Conclusion:Waveflex semi-rigid internal fixation can protect the degenerative lumbar intervertebral disc, and delay the degeneration of semi-rigid internal fixation segment and adjacent upper segment after interbody fusion, but long-term follow-up and study are needed.

Objective:To evaluate the left ventricular systolic function and synchronization of patients with early left breast cancer after breast conserving radiotherapy by layer-specific strain technique.Methods:Thirty-six patients with early left breast cancer who underwent breast surgery and radiotheraphy in Affiliated Tumor Hospital of Zhengzhou University from January 2018 to January 2019 were selected for this study. The layered strain technique was respectively applied to collect two-dimensional dynamic ultrasonic cardiograms one week before radiotherapy, one week after radiotherapy, and six months after radiotherapy. The EchoPAC 201 software was applied to analyze and obtain the global longitudinal peak strain(GLPS) and peak stain dispersion(PSD) of the epicardial layer(epi), the middle layer(mid) and endocardial layer(endo) of 17 left ventricular segments. The differences of every parameter before and after radiotherapy were compared, and the correlation of PSD and other parameters was analyzed.Results:Compared with one week before radiotherapy, the absolute values of LPSepi, LPSmid, LPSendo, and GLPS all reduced significantly one week and six months after radiotherapy, and PSD increased significantly ( P<0.05). Compared with one week after radiotherapy, the LPS absolute value of every layer and GLPS obviously reduced after six months, PSD obviously increased, the difference had statistical significance ( P<0.05). PSD and GLPS displayed negative correlation one week after radiotherapy ( r=-0.420, P<0.05), PSD and GLPS displayed negative correlation six months after radiotherapy ( r=-0.641, P<0.05). Conclusions:Layered strain technique can noninvasively and quantitatively evaluate the early changes of global and layered longitudinal peak strain and systolic synchrony of left ventricle in left breast cancer breast-conserving radiotherapy patients, and provides a new noninvasive test method for evaluating radioactive myocardial injury, and it has a certain guiding value to early clinical intervention and treatment of cardiovascular complications.

OBJECTIVE: To investigate the effects of salvianolic acid A (SAA) on cardiomyocyte apoptosis and mitochondrial dysfunction in response to hypoxia/reoxygenation (H/R) injury and to determine whether the Akt signaling pathway might play a role. METHODS: An in vitro model of H/R injury was used to study outcomes on primary cultured neonatal rat cardiomyocytes. The cardiomyocytes were treated with 12.5, 25, 50 μg/mL SAA at the beginning of hypoxia and reoxygenation, respectively. Adenosine triphospate (ATP) and reactive oxygen species (ROS) levels were assayed. Cell apoptosis was evaluated by flow cytometry and the expression of cleaved-caspase 3, Bax and Bcl-2 were detected by Western blotting. The effects of SAA on mitochondrial dysfunction were examined by determining the mitochondrial membrane potential (△Ψm) and mitochondrial permeability transition pore (mPTP), followed by the phosphorylation of Akt (p-Akt) and GSK-3β (p-GSK-3β), which were measured by Western blotting. RESULTS: SAA significantly preserved ATP levels and reduced ROS production. Importantly, SAA markedly reduced the number of apoptotic cells and decreased cleaved-caspase 3 expression levels, while also reducing the ratio of Bax/Bcl-2. Furthermore, SAA prevented the loss of △Ψm and inhibited the activation of mPTP. Western blotting experiments further revealed that SAA significantly increased the expression of p-Akt and p-GSK-3β, and the increase in p-GSK-3β expression was attenuated after inhibition of the Akt signaling pathway with LY294002. CONCLUSION SAA has a protective effect on cardiomyocyte H/R injury; the underlying mechanism may be related to the preservation of mitochondrial function and the activation of the Akt/GSK-3β signaling pathway.
Adenosine Triphosphate ; analysis ; Animals ; Animals, Newborn ; Caffeic Acids ; pharmacology ; Cell Hypoxia ; Cells, Cultured ; Glycogen Synthase Kinase 3 beta ; physiology ; Lactates ; pharmacology ; Mitochondria, Heart ; drug effects ; physiology ; Mitochondrial Membrane Transport Proteins ; drug effects ; Myocytes, Cardiac ; drug effects ; Proto-Oncogene Proteins c-akt ; physiology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; physiology

Objective: To investigate the relationship between the erythrocyte membrane protein gene mutations and the clinical severity of hereditary spherocytosis (HS). Methods: Targeted sequencings were performed on 25 HS patients, correlation between HS mutations and patients’ clinical characteristics were evaluated. Results: A total of 25 HS patients were enrolled, including 13 males and 12 females with median age of 20 (4-55) years, including 9 compensatory hemolysis patients, 9 patients with mild anemia, 3 patients with moderate anemia and 4 patients with severe anemia. Of them, 18 patients (72%) harbored HS-related mutations, including ANK1 mutation in 6 cases, SLC4A1 mutation in 6 cases, SPTB mutation in 5 cases and 1 case with EPB41 mutation. Seven patients (28%) didn’t carry common HS mutations. SPTB and SLC4A1 mutations mainly affected male patients. There was no significant difference between the age of diagnosis (P=0.130) and HGB level (P=0.585) in patients with HS mutation and those without mutation, however, the EMA binding fluorescence intensity (P=0.015), AGLT50 (P=0.032) and EOF minimal hemolytic concentration (P=0.027) were significantly different in these two groups of HS patients. Conclusion To screen erythrocyte membrane protein coding gene mutations could favor the diagnosis of HS, and patients without mutations have mild clinical phenotype.

Objective To investigate the serum levels of dickkopf-related protein 1 (DKK1) and sclerostin (SOST) in patients with axial spondyloarthritis treated with selective cyclo-oxygenase 2 inhibitor and its relation to clinical efficacy.Methods A randomized double-blind controlled trial with axial spondyloarthritis (ax-SpA) was carried out in our hospital.The data from patients in a single center was collected and analyzed.Serum DKK1 and SOST levels were measured by enzyme-linked immuno sorbent assay (ELISA)method before and after 12 weeks treatment,then correlation analysis were conducted for DKK1 and SOST levels with erythrocyte sedimentation rate (ESR),C reactive protein (CRP),Bath ankylosing spondylitis disease activity index (BASDAI),Bath ankylosing spondylitis functional index (BASFI) and SPARCC of the sacroiliac joint inflammation score.Chi-square tests were used for analyzing of categorical data.Fisher exact tests were performed when the expected frequencies were less than 5.Two independent samples t-test was used to compare the difference between groups.Single sample t-test was used to ompare the differences between data before and after treatment.Pearson or Spearman correlation was used for correlation analysis.Results After 12 weeks of treatment,a total of 116 patients completed the follow-up,including 57 cases of imrecoxib group and 59 cases of the celecoxib group.There were no statistically significant difference between the two groups (P＞0.05).The level of serum DKK1 was significantly increased after treatment [(393±137) pg/ml,vs (542±274)pg/ml,P＜0.05].The serum level of SOST increased significantly [(39±19) pg/ml vs (57±36) pg/ml,t=5.814,P＞0.05],too.The difference between the two groups was not statistically significant (P＞0.05).Spearman correlation analysis showed that serum DKK1 was positively correlated with serum SOST (r=0.226,P=0.015).A significantcorrelation was found between SOST level and ESR,CRP,finger to floor distance,left and fight lumbar side flexion and Schober's test (ESR:r=-0.379,P＜0.01;r=-0.309,P=0.001;r=-0.225,P=0.015;r=0.185,P=0.047;r=0.247,P=0.008;r=0.214,P=0.021).Conclusion Imrecoxib and celecoxib have similar efficacy on relieving the signs and symptoms of patients with ax-SpA.Short-term application of selective COX-2 inhibitors can increase DKK1 and SOST and possibly delay radiographic progression.

BACKGROUND: Gentamicin bead chain is an effective drug delivery system for treatment of osteomyelitis, but it cannot be degraded, need to be removed by second operation, and can breed pathogens. As a result, biodegradable drug delivery systems become a hotspot. Nano-hydroxyapatite/poly(β-hydroxybutyrate-co-β-hydroxyvalerate)-polyethylene glycol-gentamicin (nano-HA/PHBV-PEG-GM-DDS) is considered to be a good choice for the current predicament. OBJECTIVE: To evaluate the acute or chronic toxic reactions of the whole body and local tissues, intracutaneous stimulation, cytotoxicity and hemolytic reactions after bone remodeling and implantation of nano-HA/PHBV-PEG-GM-DDS, thus providing a new kind of material for treating osteomyelitis. METHODS: Plastic nano-HA/PHBV-PEG-GM-DDS was prepared using plastic fibrin glue as microsphere scaffold and nano-HA as the core carrier of GM that was coated with PHBV and PEG. The acute, subacute/chronic toxicity, implantation, hemolysis, cytotoxicity and intracutaneous stimulation tests were performed according to the evaluated criteria of medical implanted materials as wel as biological and animal trials recommended in GB/T16886.1-1997. RESULTS AND CONCLUSION: The plastic nano-HA/PHBV-PEG-GM-DDS was nontoxic and caused no apparent changes in liver and kidney function and serum biochemical indexes. Pathological examination showed that the implanted material was covered with tissues, and inflammation changes accorded with the general regularity of inflammatory outcomes. After implantation, the nano-HA/PHBV-PEG-GM-DDS was biodegraded and replaced by osseous tissues. The hemolytic rate of the material extract to the composite diffusion solution was 1.2%, which was below the standard criteria (5%). Human bone marrow cells cultured in vitro with the plastic nano-HA/PHBV-PEG-GM-DDS grew normally with good morphology. There was no stimulation reaction according to the criteria after the diffusion solution was subcutaneously injected into the back of the animal. These findings indicate that the plastic nano-HA/PHBV-PEG-GM-DDS for treating osteomyelitis possesses excel ent biocompatibility and security.

Objective To study the scientificity and rationality in data management of the project of Chinese Chronic Disease Clinical Research System and its Achievements Application Mode;To provide evidence and reference for the improvement of follow-up work. Methods According to the relevant management regulations, guidelines, and other relevant documents of national and international clinical research data,“Questionnaire for Research Data Management Assessment of Chinese Chronic Disease Prevention” was designed. The questionnaires were used in 10 clinical topics during the on-site inspection survey, and 20 valid questionnaires were retrieved and analyzed statistically. Results 50-60 percentage of subjects in data management and statistics were performed by the third party;70 percentage of subjects were performed by their own central monitoring;50 percentage of the subjects adopted a cooperative manner with others to develop appropriate data management systems;7 centers had system and plan for data management;Data management was carried out;implementation degree of training, database, CRF tracing, and others 7 aspects was low. Conclusion Improving the quality of data management of TCM clinical research still needs to be perfected from many aspects, and quality mode of large-scale clinical trials should be improved.