Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P＜0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.
Animals ; Disease Models, Animal ; Dopamine ; Melatonin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Retina ; Sensory Deprivation

Objective:To analyze the compatibility rules of prescriptions containing Forsythiae Fructus based on data mining and explore the anti-inflammatory mechanism of Forsythiae Fructus based on network pharmacology，so as to provide reference for the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines. Method:The prescriptions containing Forsythiae Fructus in the Dictionary of Traditional Chinese Medicine Prescriptions were collected，based on which a clinical prescription database was constructed. The Chinese herbs combined with Forsythiae Fructus and the corresponding indications were subjected to frequency statistics，association rule analysis，and complex network analysis using SPSS Statistics 26，IBM SPSS Modeler 18.0，and Gephi 9.2. The active components and targets of Forsythiae Fructus for anti-inflammation were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），BATMAN-TCM，and SEA，and the targets related to anti-inflammation from GeneCards，Online Mendelian Inheritance in Man （OMIM），CTD，and GenCLiP3. Following the analysis of protein-protein interactions （PPI） with STRING，a PPI network was constructed. The enrichment analysis was performed using Metascape，and the active component-anti-inflammation target-signaling pathway network of Forsythiae Fructus was constructed by Cytoscape 3.8.2. Result:According to the inclusion and exclusion criteria，2 245 prescriptions containing Forsythiae Fructus were harvested，involving 512 Chinese herbs，with a total usage frequency of 27 314. The Chinese herbs that were most frequently combined with Forsythiae Fructus （>800 times） were Glycyrrhizae Radix et Rhizoma （1 483 times），Scutellariae Radix （964 times），and Angelicae Sinensis Radix （842 times）. Hence，the herbal pairs "Forsythiae Fructus-Scutellariae Radix" and "Forsythiae Fructus-Angelicae Sinensis Radix" were further explored. The prescriptions containing Forsythiae Fructus could be utilized for the treatment of 29 kinds of diseases，and three representative disease categories including "carbuncle，gangrene，sores and ulcers"，"ophthalmic diseases and syndromes" and "epidemic diseases" are selected for data mining. There were 19 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Lonicerae Japonicae Flos-Angelicae Sinensis Radix" as the core herb combination for "carbuncle，gangrene，sores and ulcers". The clustering analysis revealed one multi-herb clustering group，four herbal pairs，and single herb Lonicerae Japonicae Flos，the complex network analysis four herbal modules，and the factor analysis six common factors. There were 23 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Scutellariae Radix-Angelicae Sinensis Radix" as the core herb combination for "ophthalmic diseases and syndromes". The clustering analysis revealed two multi-herb clustering groups and four herbal pairs，the complex network analysis four herbal modules，and the factor analysis five common factors. There were 28 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Menthae Haplocalycis Herba-Lonicerae Japonicae Flos" as the core herb combination for "epidemic diseases". The clustering analysis revealed three multi-herb clustering groups，one herbal pair，and two single herbs Forsythiae Fructus and Glycyrrhizae Radix et Rhizoma，the complex network analysis four herbal modules，and the factor analysis five common factors. As demonstrated by network pharmacology-based analysis，the core anti-inflammation components of Forsythiae Fructus were quercetin，luteolin，and kaempferol，and the core targets were phosphoinositide-3-kinase regulatory subunit 1 （PIK3R1），protein kinase B 1 （Akt1），and epidermal growth factor receptor（EGFR）. The biological pathways were mainly concentrated in proteoglycans in cancer，pathways in cancer，and PI3K/Akt signaling pathway，with such functions as inhibition of transcription factors，regulation of enzyme activity，and inflammation-related gene expression involved. Conclusion:This study employed a variety of data mining techniques to objectively，intuitively，and scientifically uncover the compatibility rules of Forsythiae Fructus in the treatment of high-frequency diseases. It has been found that Forsythiae Fructus is often combined with heat-clearing herbs，tonifying herbs，exterior-releasing herbs，and blood-activating and stasis-resolving herbs for diverse diseases and syndromes. Under the premise of clearing heat and removing toxin，reinforcing healthy Qi and dredging stagnation are also emphasized. According to the degree of internal heat exuberance，the heat-clearing herbs with different merits are combined. This study has revealed the unique advantages of Forsythiae Fructus in the treatment of specific diseases and syndromes as well as its multi-component，multi-target，and multi-pathway mechanisms in anti-inflammation，breaking through the limitations in modern clinical and experimental research of Forsythiae Fructus. These findings are of great significance for guiding the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines，thus better accelerating the development of Chinese medicine health industry.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

[Objective]To investigate the character of expression of NK cells and its receptors in peripheral blood of pa-tients with HBV-related acute-on-chronic liver failure(HBV-ACLF)in different phase.[Methods]There are thirteen pa-tients with HBV-ACLF in advanced phase group and thirty-three patients in plateau phase group,with thirteen healthy per-son in control group.The frequency of NK cells and expression of NK cell activating receptors(NKAR)including NKG2D, NKp30 and NKp46,NK cell inhibitory receptors(NKIR))cludingsd ate the character of including NKG2A,KIR2DL1, KIR2DL3 and KIR3DL1,NK cell killing function related factors including Perforin,GranzymeB and FasL in peripheral blood of all patients were detected by flow cytometry.[Results]The percentage of NK cells in advanced group was lower than plateau group and healthy control group(H=7.771,P=0.021).The expression of KIR3DL1 in healthy control group was high-er than advanced group and plateau group(Z=6.639,P=0.036)while the expression of FasL was significantly lower than ad-vanced group and plateau group(Z=22.5,P<0.001).[Conclusion]Patients in advanced group had lower frequency of NK cells,lower expression of inhibitory receptor KIR3DL1 and higher expression of FasL than patients in plateau group and healthy control group,which is associated with immune status of patients in different phase of liver failure.

OBJECTIVETo investigate the efficacy and safety of NOPHO-AML 2004 chemotherapy regimen for treatment of children with acute myelocytic leukemia(non-M3).

METHODSThirty-three patients aged 1-13 with acute myelocytic leukemia (non-M3) were diagnosed from January 2013 to June 2017. FAB typing showed that 1 case in M0, 4 cases in M1, 12 cases in M2, 5 cases in M4, 8 cases in M5, 1 case in M6, and 2 cases in M7; Risk stratification showed that: 19 cases in standard risk, and 14 cases in high risk. All patients were treated with NOPHO-AML 2004 chemotherapy regimen. SPSS 22.0 software was used, the Kaplan-Meier survival analysis method and Cox regression model were used for statistical analysis.

RESULTSIn the first course of treatment (AIET), among 33 child patients there were 27 cases with complete remission, and 5 cases with non-remission, thus the remission rate was 81.8%. Out of the 5 child patients without remission, 4 cases reached to the complete remission after the second course (AM), and 1 case did not remission, thus the total remission rate was 96.9%.9 cases (27.3%) underwent bone marrow recurrence and the median recurrence time was 30 months after complete continuous remission. Univariate analysis showed that age and erythrocyte transfusion frequency were significant factors to affect the early treatment response; the multiple Cox regression analysis showed that: age >7, MRD positive, erythrocyte transfusion >4 times and poor response to early treatment were independent risk factors for recurrence; Allogeneic hematopoietic stem cell transplantation(HSCT) in 8 high-risk children received enhanced chemotherapy had better efficacy as compared with the chemotherapy alone. The 3-year event-free survival rate was 59.9%, and 3-year overall survival rate was 69.2%. 33 children patients experienced varying degrees of infection and myelosuppression, or drug-related gastrointestinal reactions and allergic reactions, patients were tolerable to these side reactions after active symptomatic treatment.

CONCLUSIONNOPHO-AML 2004 chemotherapy regimen has high response rate and good tolerance, early treatment response is an important factor influencing prognosis. Age and repeated red blood cell infusions are the important factors influencing the prognosis, which promote bone marrow recurrence in AML children. For the children suffered from clinical high-risk AML, the NOPHO-AML 2004 chemotherapy regimen combined with HSCT can improve the prognosis of patients.

Adolescent ; Child ; Child, Preschool ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Leukemia, Myeloid, Acute ; Prognosis ; Remission Induction ; Treatment Outcome

OBJECTIVETo investigate clinical and epidemiological characteristics of hospitalized severe acute respiratory illnesses (SARI) patients under 15 years old registered by sentinel hospitals at 10 cities and risk factors analysis of severe illness.

METHODSThe objects of this study were 2 937 SARI patients under 15 years old registered by sentinel surveillance in internal wards, pediatrics wards and intensive care units (ICU) of 10 sentinel hospitals in 10 cities during the period from December 2009 to June 2014. We also collected case report form (CRF) of them and their throat swabs for influenza testing. The inclusion criteria was hospitalized patients who were admitted by surveillance departments, registered by SARI surveillance system, under 15 years old, meeting SARI case definition and with complete CRF. Rank-sum test was used to compare the difference of age, the duration including from onset to admission, hospital stay and from onset to discharging/death between mild illness and severe illness. Chi-square test was used to compare the difference of demographic characteristics, influenza psoitive rate, vaccination rate of influenza, chronic medical conditions and clinical characteristics between mild illness and severe illness. Logistic regression was used to analysis risk factors associated with severe illness by two stratifications from SARI surveillance protocol (< 2 years old and ≥ 2 years old).

RESULTSAmong 2 937 SARI patients under 15 years old, 97.7% (2 872/2 937) was mild illnesses, and 2.3% (65/2 937) was severe illnesses. 78.8% (2 315/2 937) was under 5 years old. The median ages of severe illness and mild illness were 0.4 and 2.0 years old (U = -6.23, P < 0.001). The proportions of severe illness and mild illness with at least one chronic medical condition were 32.3% (21/65) and 8.4% (240/2 872) (χ² = 45.03, P < 0.001). The positive rate of influenza virus was 6.5% (190/2 937), which was 6.5% (186/2 858) for mild illness and 6.2% (4/65) for severe illness (χ² = 0.08, P = 0.961). The proportion of seasonal influenza vaccination was 1.5% (42/2 853), which was 1.5% (42/2 788) for mild illness and higher than that for severe illness (0) (χ² = 6.09, P = 0.048). For under 2 years old patients, age < 11 months and with at least one chronic medical condition were risk factors for severe SARI illness, and the risk for SARI patients who was 12-23 months and without medical condition was 14.71 (5.35-40.44) and 5.61 (2.96-10.63). For ≥ 2 years old patients, age, with at least one chronic medical condition and seasonal influenza vaccination history have no association with severe illness, OR (95% CI) was 0.92 (0.80-1.05), 0.67 (0.09-5.05) and 0.85 (0.31-2.35), respectively.

CONCLUSIONMost of SARI patients registered by 10 urban sentinel hospitals were patients under 5 years old. Age < 11 months and with at least chronic medical conditions were possible risk factors of severe illness of SARI patients.

Adolescent ; Child ; Child, Preschool ; China ; Chronic Disease ; Cities ; Hospitalization ; Hospitals ; Humans ; Infant ; Influenza, Human ; Orthomyxoviridae ; Respiratory Tract Diseases ; Risk Factors ; Sentinel Surveillance ; Vaccination

The specimens of ductal carcinoma in situ (DCIS) with early invasion, and specimens collected by core needle biopsy (CNB) tend to contain limited amount of invasive component, so it is imperative to explore a new technique which can assess HER2 gene status accurately for the limited invasive cancer component in these specimens. Dual staining technique of combining immunohistochemistry (IHC) for myoepithelial cells and single or dual probe chromogenic in situ hybridization (CISH) for HER2 gene was performed on routinely processed paraffin sections from 20 cases diagnosed as having DCIS with invasive cancer. Among them, 10 had fluorescence in situ hybridization (FISH)-confirmed amplification of HER2 and 10 had FISH-confirmed non-amplification of HER2. We successfully detected HER2 genetic signals and myoepithelial IHC markers (SMM-HC or CK5/6) simultaneously on a single section in all 20 specimens. Myoepithelial markers and HER2 signals detected by dual staining assay were consistent with those by individual technique performed alone. HER2 gene amplification results determined by dual staining assay were 100% consistent with those of FISH. Dual staining technique which allows simultaneous detection of myoepithelial marker protein and cancerous HER2 gene is feasible, and it has potential to be used in clinical practice for effective determination of HER2 amplification in limited invasive component.
Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Chromogenic Compounds ; Female ; Gene Expression Profiling ; methods ; Humans ; Immunohistochemistry ; methods ; In Situ Hybridization, Fluorescence ; methods ; Neoplasm Invasiveness ; pathology ; physiopathology ; Receptor, ErbB-2 ; genetics ; metabolism ; Reproducibility of Results ; Sensitivity and Specificity

OBJECTIVETo investigate the current state of oral administration of Chinese patent medicine in treatment of chronic kidney disease (CKD) in the Westem medicine hospitals.

METHODSOutpatients of Department of Nephropathy, Peking University Third Hospital with diagnosed CKD confirmed by CKD diagnosis standard were surveyed by questionnaire in May 2009. The following patients' information was collected using the Questionnaire of the Current State of Oral Administration of Chinese Patent Medicine at CKD Clinics. (1) The present symptoms, tongue figure, pulse figure were syndrome typed referring to The Diagnosis, Syndrome Typing, and Efficacy Assessment of Chronic Renal Failure 2006 by Chinese Society of Renal Diseases, Chinese Society of Traditional Chinese Medicine. (2) Names of Chinese patent medicines and Western medicines patients use presently, the dose and dosage, names of hospitals responsible for prescriptions. (3) Patients' basic diseases including diabetes, hypertension, hyperuricemia, and so on at present. Irrational applications of Chinese patent medicines were classified according to the drug instruction and Guiding Principle of Clinical Application of Chinese Patent Medicines (issued by State Administration of Traditional Chinese Medicine). The irrationality was analyzed. Correlated factors such as age, sex, deficiency in origin syndrome, sthenia in superficiality syndrome, the nature and grade of hospitals responsible for prescriptions, total numbers of Chinese patent medicines, and primary diseases, etc. were analyzed using Logistic regression model. These factors might result in irrational application of Chinese patent medicines.

RESULTS102 questionnaires were handed out, with 78 effective ones. Of them, 41 patients (41/78, accounting for 52.6%) were taking Chinese patent medicines. Of the 41 patients, irrational application happened to 24 patients (24/41, accounting for 58.5%), absolute discrepancy of medicines and syndromes to 5 (5/41, accounting for 12.2%), repeated medication to 7 (7/41, accounting for 17.1%), and interaction to 2 (2/41, accounting for 4.9%). Logistic regression model was analyzed. Variables were screened by Enter method. The number of Chinese patent medicines had statistic significance (P<0.05).

CONCLUSIONSThe occurrence rate of irrational application of Chinese patent medicines in CKD outpatients in Westem medicine hospitals was higher. They were mainly manifested as absolute discrepancy of medicines and syndromes and repeated medication. Increased numbers of Chinese patent medicines in recipes would increase the occurrence rate of irrational application of Chinese patent medicines.

Adult ; Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Outpatients ; Phytotherapy ; utilization ; Renal Insufficiency, Chronic ; drug therapy ; Surveys and Questionnaires