Objective:This study aimed to develop and validate a scale for measuring the care competency of family caregivers in home palliative care (CCSHPC). Methods:The initial version was established based on the model for caregiver skill building/effectiveness, literature review, qualitative research, expert consultations, and quantitative research. The measurement properties included content validity, structural validity, internal consistency, reliability, measurement error, and construct validity. The survey included 381 family caregivers who had previously or were currently receiving home palliative care services in Shanghai. Results:The final scale comprised 29 items across 6 dimensions: care knowledge, daily care skills, special care skills, caregiving qualities, self-care practices, and the acquisition of social supports and resources. The cumulative variance contribution rate was 75.406%. Confirmatory factor analysis showed good model fit (χ 2 ​= ​767.146, df ​= ​357, χ 2 /df ​= ​2.149, root mean square of approximation error ​= ​0.074, root mean square residual ​= ​0.063, incremental fitting index ​= ​0.904, comparative fit index ​= ​0.903). The content validity at the scale and item levels were 0.97 and 0.86 to 1.00, respectively. The reliability of the scale was acceptable (Cronbach's α ​= ​0.954, McDonald's Omega ​= ​0.959, split-half reliability ​= ​0.886, test-retest reliability ​= ​0.931). The standard error of measurement was 4.38. Conclusions:The scale is reliable and valid, and it can be applied to measure the care competency of family caregivers in home palliative care, providing a reference for medical professionals to develop targeted intervention strategies. However, the applicability of the scale among family caregivers in different cultural and social contexts, as well as the validation of other measurement properties of the scale, requires further research.

This study investigated the role of the Composite Dietary Antioxidant Index (CDAI) in cardiovascular-kidney-metabolic (CKM) syndrome staging and mortality using NHANES 2001–2018 data from 25,155 U.S. adults. Higher CDAI quartiles demonstrated progressively reduced odds of advanced CKM stages versus Stage 0 (Q4 vs. Q1 ORs: Stage 1: 0.71 (0.56–0.91); Stage 2: 0.58 (0.45–0.74); Stage 3: 0.30 (0.20–0.47); Stage 4: 0.46 (0.35–0.60); all P < 0.05). Weighted Quantile Sum regression identified a protective effect of the antioxidant mixture against advanced CKM (OR: 0.82 (0.76–0.88); P < 0.001), primarily driven by vitamins A (weight = 0.357), C (0.290), and selenium (0.212). In CKM patients, higher CDAI was associated with significantly lower all-cause (Q4 vs. Q1 HR: 0.63 (0.57–0.70)), cardiovascular (HR: 0.63 (0.51–0.78)), and non-cardiovascular mortality (HR: 0.63 (0.56–0.72); all P < 0.001). Nonlinear analyses revealed threshold effects for all-cause and non-CVD mortality at CDAI ≈ 0. These findings indicate that elevated CDAI is robustly associated with less severe CKM staging and reduced mortality, supporting dietary antioxidant optimization for CKM management and risk stratification.

The U.S. Food and Drug Administration (FDA) suggests the “Reference-Scaled Average Bioequivalence” (RSABE) method in the average bioequivalence (ABE) study of highly variable drugs. The classic sample size estimation method for grouping sequential design (GSD) of the RSABE method is a single-stage sample size multiplied by the inflation factor. This study proposed a new method for calculating the sample size for the GSD of the RSABE: using simulation experiments directly. In this work, our focal point is on a two-stage GSD that adheres to the Pocock guideline, comprising a single interim analysis and a final analysis. We consider that the sample size of the two stages is equal; that is, the interim analysis is carried out at 50% of the information fraction. Extensive Monte Carlo simulations have shown that the new method is more accurate in estimating sample size than the inflation factor method, and the type I error rate is controlled below 5% in all conditions. In 90% power semireplicate studies, the average sample size required for the Pocock design is only 40% to 90% of the single-stage design sample size.

Sirtuin 5 (SIRT5), localized in the mitochondria, has been identified as a protein desuccinylase and demalonylase in the mitochondria since the depletion of SIRT5 boosted the global succinylation and malonylation of mitochondrial proteins. We investigated the role of SIRT5 in diabetic cardiomyopathy (DCM) and identified the mechanism regarding lysine demalonylation in this process. Wild-type and SIRT5 knockout mice were induced with DCM, and primary cardiomyocytes and cardiac fibroblasts extracted from wild-type and SIRT5 knockout mice were subjected to high glucose (HG). SIRT5 deficiency exacerbated myocardial injury in DCM mice, aggravated HG-induced oxidative stress and mitochondrial dysfunction in cardiomyocytes, and intensified cardiomyocyte senescence, pyroptosis, and DNA damage. DCM-induced SIRT5 loss diminished glutathione S-transferase P (GSTP1) protein stability, represented by significantly increased lysine malonylation (Mal-Lys) modification of GSTP1. SIRT5 overexpression alleviated DCM-related myocardial injury, which was reversed by GSTP1 knockdown. Reduced SIRT5 transcription in DCM resulted from the downregulation of SPI1. SPI1 promoted the transcription of SIRT5, thereby ameliorating DCM-associated myocardial injury. However, SIRT5 deletion resulted in a significant reversal of the protective effect of SPI1. These observations suggest that SPI1 activates SIRT5 transcriptionally to mediate GSTP1 Mal-Lys modification and protein stability, thus ameliorating DCM-associated myocardial injury.

The nitrogen permease regulator-like-2 (NPRL2) gene is a candidate tumor suppressor gene, which has been identified in the 3p21.3 human chromosome region. Decreased expression levels of NPRL2 have been observed in colorectal cancer (CRC) tissues, however, the function of NPRL2 in CRC progression remains to be fully elucidated. The present study investigated the biological characteristics of the HCT116 and HT29 CRC cell lines overexpressing exogenous NPRL2. NPRL2 recombinant lentiviral vectors were also constructed and transfected in the present study. Cell growth was determined using a Cell Counting Kit-8 assay and a colony formation assay. The cell cycle and rate of apoptosis were assessed using flow cytometric analysis. Transwell assays were used to evaluate cell invasion. The protein expression of phosphorylated (p)-AKT and caspase 3, B-cell lymphoma 2 (Bcl2) and Bcl-2-associated X protein apoptosis-associated genes, were detected using western blotting. The results revealed that NPRL2 overexpression inhibited cell growth, induced cell cycle G(1) phase arrest, promoted apoptosis and inhibited invasion in the two human CRC cell lines. Furthermore, the protein expression levels of p-AKT and Bcl2 were significantly reduced in the NPRL2-transfected HCT116 and HT29 cells, compared with the mock-transfected group and control group, while the protein expression of caspase-3 was increased. Therefore, NPRL2 acted as a functional tumor suppressor in the CRC cell lines.

Background The Ministry of Health of China conducted a study targeting in single-disease quality control in 2009, aimed to strengthen quality management and improve health care services. This study retrospectively investigated the trends of quality indicators for six monitored diseases 2011-2017 to evaluate the improvement of care quality for the first batch of single-disease. Methods We extracted data from the National Specific (Single) Disease Monitoring System for 2011-2017. We focused on six conditions: acute myocardial infarc-tion, heart failure, community-acquired pneumonia, coronary artery bypass graft, hip / knee replacement, and acute ischemic stroke. A total of 56 quality indicators (QIs) were adopted to monitor the quality change and determine the trends in care quality. We also calculated the hospital process composite performance (HPCP) using a denominator-based weighting method for each hospital per year. The es-timated annual percentage changes (EAPC) 2011-2017 were calculated at nation-al and regional levels.Results The results showed that use of four QIs had significant downward trends, whereas 25 QIs (including reversed indicators) showed significant upward trends from 2011 to 2017. The greatest improvement was observed in CAP-4 (antibiotic treatment within four hours after admission to the hospital for critical pneumonia) in the central region (EAPC = 48.36, 95% CI = 15.92-89.87); while the largest de-crease appeared in AIS-1 (thrombolytic therapy within 4.5 hours of symptom onset) in the western region (EAPC =-13.44, 95% CI =-24.98,-0.11). An increased HPCP was observed in four diseases nationwide, but not for acute myocardial infarction and heart failure. However, there were significant differences across regions in the process of care and outcomes, with the performance of Eastern and Western regions showing remarkable advantages compared with the Central region.Conclusions We provide evidence for major advancement in care quality in Chi-na nationwide. However, the improvement of care in China was unbalanced geographically and should be carefully considered. Future challenges include expanding the coverage of quality monitoring, greater delivery efficiency, and re-gion-balanced health care.

Background. It is well-known that dysfunctions of vascular smooth muscle cells (VSMCs) act an essential part in vascular complications of diabetes. Studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) play a crucial role in regulating cell functions. However, their influence on the proliferation, calcification, and autophagy of VSMCs remains to be further explored. Therefore, this study elucidates the role and mechanism of hsa_circRNA_0008028 in high glucose- (HG-, 30 mM) treated VSMCs in vitro. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was chosen to detect the levels of hsa_circRNA_0008028, miR-182-5p, and tribble 3 (TRIB3). Then, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to predict and verify the binding relationship between miR-182-5p and hsa_circRNA_0008028 or TRIB3. Cell counting kit-8 assay, 5-ethynyl-2 ′ -deoxyuridine (EdU) staining, corresponding commercial kits, and western blotting were used to measure indexes reflecting cell viability, proliferation, calcification, and autophagy of VSMCs, respectively. Results. In HG-induced VSMCs, hsa_circRNA_0008028 and TRIB3 were highly expressed, whereas miR-182-5p decreased. Meanwhile, cell proliferation, calcification, and autophagy could be repressed by silencing of hsa_circRNA_0008028. However, these effects can be eliminated by miR-182-5p inhibition. Furthermore, it was demonstrated that hsa_circRNA_0008028 could promote the expression of TRIB3, a target of miR-182-5p, by directly sponging miR-182-5p. The expression of TRIB3 was suppressed by hsa_circRNA_0008028 knockout, which was rescued by miR-182-5p inhibition. Conclusion. This study reveals that hsa_circRNA_0008028 can act as a sponge of miR-182-5p and promote HG-induced proliferation, calcification, and autophagy of VSMCs partly by regulating TRIB3.

MicroRNAs are widely considered to be involved in the pathogenesis of atherosclerosis. Whereas the importance of miR-30a-5p as a tumor growth-promoting factor has been extensively studied, the relationship between this particular microRNA and atherosclerosis remains to be clarified. In this study, the role of miR-30a-5p in the formation of foam cells from THP-1-derived macrophages was investigated. It was found that miR-30a-5p could robustly regulate the pathological process of atherosclerosis by inhibiting autophagy and increasing the accumulation of lipids, the expression of inflammatory factors, and the apoptosis of macrophages. These results provide guidance for future assessments of the progression of atherosclerosis and for the development of intervention targets for the treatment of this disease.

Gemcitabine (GEM) and its derivatives of deoxycytosine is a promising anticancer candidate which is effective for the treatment of various cancers including lung cancer via cascade targetting Erk/Mek/Raf/Ras pathway and blocking the proliferation of the tumor cells. In this present work, we have described reduced graphene oxide (rGO) in the presence of anticancer utilizing ascorbic acid as reducing agents for lung cancer treatment. GEM reduced graphene oxide (termed as GEM-rGO) has resulted in a smooth and transparent morphological surface, which was confirmed by various spectroscopical investigations. The anticancer drug-loaded rGO has displayed remarkable cytotoxic activities against a panel of lung cancer cell lines when compared to the untreated lung cancer cells. Further, we examined the morphological observation of the cancer cell death was monitored through the fluorescence microscopic examinations. In addition, the cell deaths of the lung cancer cells were observed by the flow cytometry analyses. In addition, the non-toxic nature of potent GEM-rGO and GEM-rGO + NIR was confirmed by in vivo systemic toxicity analysis. Besides, the higher safety feature of the GEM-rGO and GEM-rGO + NIR was evidenced by histological analyses of the mice organs. The subcutaneous injection of GEMrGO and GEM-rGO + NIR into mice bearing A549 xenografts more effectively inhibited the tumor than the free GEM. Based on the outcomes, we can summarise that the GEM reduced graphene oxide (GEM-rGO) can be used as a promising drug candidate for the treatment of lung cancer in the future.

The critical importance of circular RNAs (circRNAs) in human cancers, including ovarian cancer, has been discovered in the recent years. However, the roles of circ_0007841 in ovarian cancer remain unknown. In the current study, it was found that circ_0007841 expression was upregulated in ovarian cancer tissues and cell lines. Upregulation of circ_0007841 in patients with ovarian cancer predicts poor prognosis. Loss-of-function experiments discovered that circ_0007841 knockdown suppressed the proliferation, migration and invasion of ovarian cancer cells in vitro and in vivo. In terms of mechanism, circ_0007841 worked as a competing endogenous RNA (ceRNA) for miR-151-3p to facilitate MEX3C expression. Restoration of MEX3C level recovered the proliferation, migration and invasion of ovarian cancer cells. In conclusion, this study demonstrated that circ_0007841/miR-151-3p/MEX3C axis exerted important oncogenic functions in ovarian cancer.

背景 消化道瘘是外科手术的难治性并发症之一.随着内镜技术的进步,内镜下治疗消化道瘘也逐步发展,与外科手术相比,具有安全、微创、低治疗成本等诸多优势.病例简介 我院收入了一例以腹痛及反复腹泻为主要症状的66岁的女性患者.内镜下发现一处位于直肠与乙状结肠交界处的结肠瘘,瘘腔内可见大量白色脓性物.应用结肠镜下经肛金属夹固定双腔胃管并持续冲洗成功治愈.结论 经肛窦道腔置入双腔胃管持续冲洗是一种微创、简单、经济且有效的治疗结肠瘘的方法,金属夹固定双腔胃管可保证冲洗效果.

Leucine-rich α2-glycoprotein1 (LRG1), a pleiotropic protein, plays a pathogenic role in multiple human diseases. However, its pathophysiological function in ischemia/reperfusion injury remains unclear. In this study, we discussed the function and mechanism of LRG1 in acute ischemic stroke from both basic and clinical research points of view. Mice underwent transient middle cerebral artery occlusion (tMCAO) surgery 2 weeks after LRG1 was overexpressed by the delivery of adeno-associated virus (AAV). For wild-type mice, both the protein and the transcript of LRG1 in the brain tissue were elevated after tMCAO. Meanwhile, the serum levels of LRG1 were decreased after tMCAO. The neuronal injury was shown aggravated in the AAV-LRG1 group (AAV-LRG1 mice with tMCAO) through infarction volume, neurological score, HE, and Nissl staining. Meanwhile, LRG1 significantly enhanced apoptosis and autophagy during tMCAO, as detected by caspase3, Bax, Bcl-2, LC3II/LC3I, Beclin1, p62, and a TUNEL assay. Furthermore, by overexpression of LRG1, the protein of ALK1 was upregulated and the TGFβ-smad1/5 signaling pathway was activated upon tMCAO. We also showed that patients with acute cerebral infarction had lower serum levels of LRG1 compared to healthy controls. In addition, LRG1 levels were associated with infarction volume, stroke severity, and prognosis in patients with supratentorial infarction. Taken together, the data from this study revealed that LRG1 promoted apoptosis and autophagy through the TGFβ-smad1/5 signaling pathway by up-regulating ALK1, which exacerbates ischemia/reperfusion injury.

Introduction: Gallstone is one of the most common digestive health issues worldwide. Although cholecystectomy is widely practiced in treating symptomatic gallstones, it is still controversial whether the gallbladder should be resected or preserved. Flexible endoscopic trans-rectal or trans-colonic pure natural orifice transluminal endoscopic surgery (NOTES) has been investigated in experimental studies suggesting this approach can be an attractive option. However, technical obstacles exist, such as the risks of fecal contamination and peritoneal infection, safe entrance into the peritoneal cavity, reliable entry site closure, as well as spatial orientation. These are challenging issues preventing trans-rectal or trans-colonic NOTES in clinical application. To tackle these obstacles, the authors successfully developed a detachable endo-colonic occlusion balloon in order to keep the distal colonic and rectal lumen clean and aseptic by occluding the transverse colonic lumen. This device enables trans-rectal endoscopic procedures. This study’s goals are to evaluate the feasibility, safety, and efficacy of pure NOTES flexible endoscopic trans-rectal gallbladder preserving cholecystolithotomy (TRGPC). Methods: A total of 40 patients (average, 44.4 years) were enrolled in this prospective cohort study. A 2 cm NOTES entry was created on the anterior wall of the rectum and a 1.5 cm cholecystomy incision was made. After all gallstones were removed, the gallbladder and rectal entry stomas were closed endoscopically. Results: The pure NOTES trans-rectal procedure was technically successful in all patients. The technical success rate was 100% and no serious complications occurred in this cohort. The mean operation time was 158 min (73-472 min). Post-operative leucocytosis developed in 4 patients. Bile peritonitis occurred in 1 patient and was managed medically. The mean post-operative hospital stay was 6.3 days. During 6 and 12 months follow-up, asymptomatic gallstone recurred in 3 patients, accounting to 7.5%. Conclusion: Our work is the first to report on the feasibility, safety, and efficacy of pure NOTES TRGPC. Complete avoidance of skin incision may offer the advantages of decreased post-operative pain, quicker recovery, shorter hospital stay, and lower cost as well. TRGPC provides a novel and alternative approach in the management of symptomatic gallstones. This is the first reported series of such procedure. TRGPC is feasible, safe, and effective in treating gallstones without cholecystectomy.

BACKGROUND:Large gap exists between clinical practice and recommended care and large room exists for the improvement of care quality for non-small cell lung cancer (NSCLC) in China. Results of some studies have shown that assessment of care quality can help to make improvement and the development of quality indicators is deemed as the initial and most essential part. Yet there is no such an indicators system specifically suitable for Chinese health care system. The goal of the study is to set up a group of Chinese quality indicators for NSCLC care and make it the first step towards the improvement of NSCLC care quality in China.METHODS:We constructed a new indicator framework based on the characteristics of NSCLC care and the nature of Chinese health care system. Under the new framework, potential indicators were collected and a 3-round modified Delphi process was conducted by a national multi-disciplinary Expert Panel to develop a set of indicators until they reached the final consensus.RESULTS:A new indicator framework (structure, process, communication, management of symptoms or treatment toxicity and outcome) was developed. Seventy four indicators were extracted from guidelines and relevant literatures as potential indicators; 43 indicators plus 1 suggested indicator were remained after the discussion of Round 1; questionnaires of Round 2 were rated by Expert Panel and 19 indicators met the inclusion criteria and entered Round 3; 2 of the eliminated indicators in Round 2 were retrieved by the Expert Panel at the in-person meeting (Round 3). Therefore, 21 indicators got the final consensus of the Expert Panel.CONCLUSIONS:Guided by the new indicator structure, a set of indicators suitable for Chinese healthcare system was developed and can be utilized to measure and improve the care quality of non-small cell lung cancer.

Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC) patients with stages II and III CRC, which widely different in prognosis and treatment, by immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation and invasion in vitro. Denovirus shRNA knockdown of PTBP1 inhibited colorectal cancer growth in vivo. Furthermore, PTBP1 regulates alternative splicing of many target genes involving in tumorgenesis in colon cancer cells. We confirmed that the splicing of cortactin exon 11 which was only contained in cortactin isoform-a, as a PTBP1 target. Knockdown of PTBP1 decreased the expression of cortactin isoform-a by exclusion of exon 11. Also the mRNA levels of PTBP1 and cortactin isoform-a were cooperatively expressed in colorectal cancer tissues. Knocking down cortactin isoform-a significantly decreased cell migration and invasion in colorectal cancer cells. Overexpression of cortactin isoform-a could rescue PTBP1-knockdown effect of cell motility. In summary the study revealed that PTBP1 facilitates colorectal cancer migration and invasion activities by inclusion of cortactin exon 11.

CXCR3, a G-protein coupled chemokine receptor, has been found to be overexpressed in many tumors and act as an independent prognostic marker. However, it is still unclear whether CXCR3 is involved in gastric cancer progression. In this study, we found that CXCR3 was markedly expressed in gastric cancer cells and tissues. High CXCR3 expression correlated with advanced tumor stage, vascular invasion, lymph node metastasis and poor survival of gastric cancer patients. Activation of CXCR3 by one of its ligands CXCL10 promoted the invasion and migration of gastric cancer BGC-823 and MGC-803 cells, and increased the secretion and activities of MMP-2 and MMP-9. However, the effects of CXCL10 on gastric cancer cells were attenuated by CXCR3 siRNA transfection. Furthermore, overexpression of CXCR3 enhanced CXCL10-mediated cell invasion and migration of gastric cancer MKN28 cells. In addition, CXCR3 time-dependently induced activation of AKT. PI3K/AKT pathway was required for CXCR3-mediated gastric cancer cell invasion, migration and MMP-2/9 production. Together, our findings suggest that CXCL10/CXCR3 axis promotes gastric cancer cell invasion and migration by upregulating MMP-2 and MMP-9 production via PI3K/AKT pathway. Thus, CXCR3 could be a potential target for the gastric cancer treatment.

Ovarian cancer is the main cause of cancer mortality in gynecological tumors around the world. Drug resistance to a variety of chemotherapeutics continue to be one of the main causes of treatment failure. In a previous study, it was demonstrated that STK17A, a proapoptotic gene, was significantly downregulated in acquired resistance phenotypes of colon cancer cells that are resistant to oxaliplatin and 5-fluorouracil. Therefore in the present study, the association between STK17A expression and ovarian cancer with initial drug resistance was investigated and the influence of STK17 on ovarian cancer cell proliferation and doubling time. In the present study, ovarian cancer cell lines that express low levels of STK17A were established by targeting STK17A with specific siRNA. In addition, up-regulation of STK17A was established in ovarian cells by pCDNA3flu/STK17A. The sensitivity of the transfected cells and controls to paclitaxel, carboplatin was examined by MTT assay, and the levels of proliferation and apoptosis were analyzed by flow cytometry. In the cells that were transfected with siRNA resulting in reduced expression of STK17A, the 50% inhibitory concentration (IC50) of the chemotherapy drugs paclitaxel and carboplatin was increased compared with control cells (P<0.05). By contrast, in the cells that overexpressed STK17A following treatment with pCDNA3flu/STK17A, the IC50 of the chemotherapy drugs reduced in each case, and was significantly lower compared with the control (P<0.05). There was a variable susceptibility to carboplatin and paclitaxel resulting from altering the levels of STK17A expression in ovarian cancer cell lines. The growth of STK17A/siRNA transfected cells was promoted compared with that of the control cells and accordingly their cell doubling time was shortened.

Objective: To explore the role of preclinical small-class teaching mode in cultivating the medical students' abilities of clinical thinking, analysis and operating, and summarized the teaching experience. Methods: Fifty undergraduates students of 2011-2012 from Lanzhou University School of Stomatology were divided into two groups randomly (experimental group and control group, n = 25). Students in the experimental group will be arranged with small class every morning during the internship period while the control group not. The clinical teaching involves some normal operation of the oral medicine such as pit and fissure sealant, various hole filling, direct or indirect pulp capping, RCT (pulp exposing and seam exposing roof, root canal length measuring, root canal cleaning, root canal disinfectant, root canal filling), scaling and statistics after the internship period. Results: Most students hold a supportive attitude toward this teaching mode. They have a good impression on mainly 4 aspects of this teaching mode. 78.83% of the students prefer the small class form, 88.40% of the students prefer preparing before class, 84.40% of the students prefer the teaching content, 99.70% of the students prefer the teaching attitude. This result reveals that this teaching mode is recognized by the majority. 39.58% of the students think it has an ideal effect on operation ability, 49.57% of the students think it has an ideal effect on communication skill, 21.69% of the students think it has an ideal effect to link with theoretical knowledge and 48.40% of the students think it has an ideal effect on clinical practice. The total number of cases completed by the control group/ experimental group were fissure sealant (150/200), direct or indirect pulp capping (55/62), scaling and root planning (187/200), RCT (96/208), respectively. The mean time of muster by the control group / experimental group were fissure sealant (3/2) weeks, direct or indirect pulp capping (5/3) weeks, scaling and root planning (9/5) weeks, RCT (10/6) weeks, respectively. Conclusion: The preclinical small-class teaching mode contributes to master the clinical skills, and then improve the effect of practice. It is one of the ways to improve the clinical skill level in the early clinical practice of medical students.