Assessment of lisdexamfetamine on executive function in rats: A translational cognitive research.

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.

Comparative transcriptomic analysis reveals differences in MADS-box genes of different hypericum in Changbai Mountains.

To explore the differences between the hypericum in the Changbai Mountains, we carried out a transcriptome analysis of two common hypericums in the area, which was Hypericum attenuatum Choisy and Hypericum longistylum Oliv. We screened the MADS-box genes to analyze divergence time and evolutionary selection expression, and determine their expression levels. The results showed that we detected 9287 differentially expressed genes in the two species, of which shared 6044 genes by the two species. Analysis of the selected MADS genes revealed that the species was in an environment adapted to its natural evolution. The divergence time estimation showed that the segregation of these genes in the two species was related to the changes of external environment and genome replication events. The results of relative expression showed that the later flowering period of Hypericum attenuatum Choisy was related to the higher expression of the SVP (SHORT VEGETATIVE PHASE) and the AGL12 (AGAMOUS LIKE 12), while the lower expression of the FUL (FRUITFULL).

Efficiency analysis and management strategies of hospital beds based on diagnosis-related groups / 中华医院管理杂志

Objective:To improve the evaluation method of hospital beds efficiency based on diagnosis-related groups (DRG), and to provide a basis for hospitals to allocate beds reasonably and improve bed efficiency.Methods:Taking a tertiary hospital in Beijing as the research object, the types of beds were evaluated by the beds utilization matrix with the time consumption index as the X-axis and the bed utilization rate as the Y-axis. The types of beds in the department were divided into efficiency type, pressure type, turnover type, and idle type. The efficiency of medical services and the level of diagnosis and treatment were evaluated by the weight of DRG per bed. The calculation method of theoretical number of beds was improved by incorporating hospital case mix index as a risk adjustment factor into the formula to evaluate the status of beds allocation. Combining the bed type, DRG weight per bed, and bed allocation status, the improvement emphasis and management strategy of bed utilization could be comprehensively analyzed.Results:Among the 24 departments in the hospital, there were 5, 9, 1 and 9 departments being efficiency type, pressure type, turnover type and idle type, respectively. The weight per bed of 11 departments was higher than the average level of the hospital. There were 16, 5, and 3 departments with appropriate, fewer, and excessive beds, respectively.Conclusions:The comprehensive analysis of beds utilization type, allocation status and weight of each bed based on DRG is an effective method to evaluate the efficiency of hospital beds, and can provide decision-making basis for hospital bed resource allocation, hospital operation focus adjustment, and subject development planning.

Effects of probiotics on intestinal flora, intestinal function and T lymphocyte level in patients with cervical cancer after radiotherapy / 中国基层医药

Objective:To investigate the effects of probiotics on intestinal flora, intestinal function, and T lymphocyte level in patients with cervical cancer after radiotherapy.Methods:A total of 92 patients with cervical cancer who underwent pelvic radiotherapy in The Second Affiliated Hospital of Zhengzhou University from September 2020 to February 2022 were included in this study. They were randomly divided into control and experimental groups ( n = 46/group). The patients in the experimental group took probiotics during radiotherapy, while the patients in the control group did not take probiotics during radiotherapy. The amount of intestinal flora, D-lactic acid, diamine oxidase, and T lymphocyte subset levels pre- and post-radiotherapy were compared between the two groups. Urinary lactulose (L) and mannitol (M) concentrations were determined in each group. Urinary excretion ratios of L to M were calculated. Results:After 10, 15, and 20 times of radiotherapy and after all radiotherapies, the amount of Escherichia coli and Enterococcus in the experimental group was significantly lower than that in the control group ( F = 128.60, 224.99, all P < 0.05). The amount of Bifidobacteria and Lactobacilli in the experimental group was significantly higher than that in the control group ( F = 2 065.46, 948.23, both P < 0.05). After 10, 15, and 20 times of radiotherapy and after all radiotherapies, plasma D-lactic acid level in the experimental group was (9.34 ± 1.63) μg/L, (9.15 ± 1.36) μg/L, (8.68 ± 1.06) μg/L, and (8.05 ± 0.82) μg/L, respectively. After 10, 15, and 20 times of radiotherapy and after all radiotherapies, plasma diamine oxidase level in the experimental group was (86.34 ± 20.25) μg/L, (84.28 ± 17.45) μg/L, (80.40 ± 13.35) μg/L, and (76.85 ± 10.87) μg/L, respectively, and urinary excretion ratio of L to M in the experimental group was (1.84 ± 0.16), (1.55 ± 0.12), (1.26 ± 0.09), (0.98 ± 0.06), respectively, all of which were significantly lower than those in the control group ( F = 121.60, 31.73, 417.84, all P < 0.05). After 10, 15, and 20 times of radiotherapy and after all radiotherapies, CD4 + level in the experimental group was (39.80 ± 4.90)%, (40.92 ± 5.30)%, (42.52 ± 6.14)%, (43.83 ± 6.55)%, respectively, CD4 +/CD8 + was (1.52 ± 0.25), (1.63 ± 0.22), (1.71 ± 0.39), (1.83 ± 0.22), respectively, all of which were significantly higher than those in the control group ( F = 58.69, 31.07, all P < 0.05). Conclusion:Probiotics can improve the status of intestinal flora and intestinal barrier function in patients with cervical cancer after radiotherapy, and simultaneously improve the cellular immune function of patients.

Mechanisms of cholesterol metabolism imbalance in a PA-induced non-alcoholic fatty liver disease cell model / 中国药科大学学报

@#Liver cholesterol metabolism disorder plays an important role in the development of non-alcoholic fatty liver disease (NAFLD).In order to reveal the molecular mechanism of cholesterol homeostasis imbalance induced by saturated fatty acids, HepG2 cells were stimulated with palmitic acid (PA).Lipids accumulation was analyzed by Oil Red O staining, intracellular triglyceride and cholesterol quantification.The level of genes and proteins related to cholesterol homeostasis was measured by RT-qPCR and western blotting.Additionally, intracellular bile acids and mitochondrial oxysterols were detected by LC-MS/MS.The results demonstrated that intracellular lipids such as TG and TC were significantly increased in the model with PA stimulation.Although no significant difference was detected in genes related to cholesterol synthesis and uptake, the protein expression of ABCG5 and LXRα were significantly down-regulated, indicating a decrease in cholesterol efflux.Meanwhile, the gene expression of STARD1 and CYP7B1, which are responsible for bile acid alternative synthesis, were markedly enhanced, along with a significant increase of cholesterol and 27-OHC in mitochondria and CDCA in cells.These results suggested that PA overload may disrupt cholesterol homeostasis by inhibiting cholesterol efflux and promoting bile acids synthesis.

Practice and benefit of national standardized management of type 2 diabetes in Yulin City / 西安交通大学学报(医学版)

【Objective】 To investigate the practice and benefit of national standardized management of type 2 diabetes in Yulin City. 【Methods】 We recruited the adult type 2 diabetes patients who sought medical help at our hospital from May 2020 to October 2022 as subjects. We collected their basic information (sex and age); measured height, weight, waist and hip circumference, and blood pressure; calculated body mass index (BMI); and detected blood glucose, c-peptide, HbA1c, biomarkers, urinary microalbumin, sensory nerve conduction velocity of lower limbs, ABI, and subcutaneous and visceral fat at the time of MMC recruited and the end of six months. T test and Mann-Whitney U rank sum test were used for measurement data and χ2 test or Fisher’s exact probability method for counting data to analyze the data. 【Results】 After 6 months, the levels of fasting blood glucose, postprandial blood glucose, HbA1c, and visceral and subcutaneous fat in all the patients decreased, but the level of fasting c-peptide increased compared with the baseline (all P<0.05). Secondly, compared with the baseline, the control rate of HbA1c (35.21% vs. 13.71% ) and the comprehensive control rate (13.97% vs. 7.26% ) were both significantly increased at six months (P<0.05). Thirdly, after 6 months, the levels of fasting blood glucose, postprandial blood glucose, HbA1c, TG, TC, and UA were decreased more, while the fasting c-peptide and postprandial c-peptide were increased more in the patients of the HbA1c standard group (HbA1c<7% ) than those of the non-standard group. 【Conclusion】 The multiple benefits of blood glucose, blood lipid, uric acid and islet function can be achieved by taking type 2 diabetes patients into MMC. Meanwhile, the rates of HbA1c control and comprehensively reaching the standard are significantly increased. Therefore, MMC can explore a new way for the management of type 2 diabetic patients in this area.

Status and associated factors of mild cognitive impairment among the elderly in Shanghai community / 上海预防医学

ObjectiveTo explore the status of mild cognitive impairment （MCI） among the elderly in Shanghai communities， and to identify the factors associated with MCI. MethodsThe Montreal Cognitive Assessment-Basic （MoCA-B） was used to screen for MCI in elderly adults. Logistic regression analysis was conducted to identify the factors associated with MCI. ResultsAmong 629 participants， 226 （35.90%） were positive for MCI. Older age （OR=1.04， 95%CI： 1.01-1.07）， lower family income （average OR=2.20， 95%CI： 1.01-4.80； poor OR=2.59， 95%CI： 1.03-6.50）， hearing impairment affecting daily life （OR=1.86， 95%CI： 1.19-2.91）， and anxiety symptoms （OR=1.58， 95%CI： 1.02-2.44） were associated with the positive for MCI. Living in central urban area （OR=0.57， 95%CI： 0.37-0.89） and having higher social support （OR=0.97， 95%CI： 0.94-1.00） were protective factors for MCI. ConclusionThe current status of MCI among the elderly in Shanghai communities is not optimistic. It is important and necessary to establish the cognitive-friendly community for the elderly.

Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System / 神经科学通报·英文版

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

Dietary exposure level of to perfluorinated compounds and its relationship with perinatal adverse events in pregnant women in Xuhui District of Shanghai / 环境与职业医学

Background Perfluorinated compounds (PFCs) are persistent organic pollutants. Dietary exposure to PFCs among pregnant women may lead to elevated risks of adverse events during pregnancy and postpartum depression. Objective To estimate potential risk of dietary exposure to PFCs among pregnant women in Xuhui District, Shanghai, and the relationship between dietary PFCs exposure and risks of adverse events during pregnancy and postpartum depression. Methods This study was a small cohort study which recruited women residing in Xuhui District from July 2017 to September 2018. All information was collected through questionnaires by trained investigators. Basic information and dietary information were collected at the time of inclusion, where the dietary information was obtained through the Food Frequency Questionnaire (FFQ). A follow-up visit was conducted within 42 d after delivery to collect the occurrence of adverse events during pregnancy and postpartum depression. According to the results of dietary survey, sampling and PFCs level testing were conducted on commercially available staple foods, poultry and livestock meat, aquatic products, vegetables, milk and dairy products, eggs, etc. The food sampling points covered all subdistricts in Xuhui District, including farmers' markets, supermarkets, convenience stores, and shops. Daily exposure level and hazard ratio (HR) of PFCs per capita were calculated according to the dietary survey and laboratory testing. Logistic regression was used to estimate the relationship between PFCs exposure and the risks of adverse events during pregnancy and postpartum depression. The levels of PFCs exposure were further divided into 4 groups according to interquartile range, and OR and Ptrend value were calculated respectively. Results A total of 345 pregnant women were recruited in this study, whose average age was (29.61±4.92) years. Among them, 26.37% subjects reported at least one adverse event during pregnancy, and 30.14% subjects reported an Edinburgh Postnatal Depression Scale (EPDS) score ≥12. A total of 132 food samples were collected and tested, and PFCs were positive mainly in milk and dairy products, poultry meat, livestock meat, eggs, fresh water products, and sea water products. The PFCs positive rate in fresh water products was the highest, reaching 100%. The average concentration of PFCs in the positive samples was 0.018-2.10 μg·kg−1. The HR of PFCs was 4.44. A higher risk of postpartum depression was found along with a higher perfluorooctane sulfonate (PFOS) exposure level (Ptrend=0.02). Conclusion Dietary PFCs exposure may pose a health risk to pregnant women. The study findings suggest that decreasing the intake of freshwater products might help reduce the risk of PFCs exposure among pregnant women in Xuhui district, Shanghai.

Real-world Efficacy and Safety Comparison of Neoadjuvant Treatment of HER2-positive Breast Cancer with TCbHP Versus AC-THP / 肿瘤防治研究

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

Assessing professional identity formation (PIF) amongst medical students in Oncology and Palliative Medicine postings: a SEBA guided scoping review.

BACKGROUND: Introduction to a multi-professional team who are working and caring for the dying, and facing complex moral and ethical dilemmas during Oncology and Palliative Medicine postings influence a medical student's professional identity formation (PIF). However, limited appreciation of PIF, inadequate assessments and insufficient support jeopardise this opportunity to shape how medical students think, feel and act as future physicians. To address this gap, a systematic scoping review (SSR) of PIF assessment methods is proposed. METHODS: A Systematic Evidence-based Approach (SEBA) guided SSR of assessments of PIF in medical schools published between 1st January 2000 and 31st December 2021 in PubMed, Embase, ERIC and Scopus databases was carried out. Included articles were concurrently content and thematically analysed using SEBA's Split Approach and the themes and categories identified were combined using SEBA's Jigsaw Perspective. The review hinged on the following questions: "what is known about the assessment of professional identity formation amongst medical students?", "what are the theories and principles guiding the assessment of professional identity formation amongst medical students?", "what factors influence PIF in medical students?", "what are the tools used to assess PIF in medical students?", and "what considerations impact the implementation of PIF assessment tools amongst medical students?". RESULTS: Two thousand four hundred thirty six abstracts were reviewed, 602 full-text articles were evaluated, and 88 articles were included. The 3 domains identified were 1) theories, 2) assessment, and 3) implementation in assessing PIF. Differing attention to the different aspects of the PIF process impairs evaluations, jeopardise timely and appropriate support of medical students and hinder effective implementation of PIF assessments. CONCLUSION: The Krishna-Pisupati model combines current theories and concepts of PIF to provide a more holistic perspective of the PIF process. Under the aegis of this model, Palliative Care and Oncology postings are envisaged as Communities of Practice influencing self-concepts of personhood and identity and shaping how medical students see their roles and responsibilities as future physicians. These insights allow the forwarding of nine recommendations to improve assessments of PIF and shape the design of a PIF-specific tool that can direct timely and personalized support of medical students.

A systematic scoping review moral distress amongst medical students.

BACKGROUND: Characterised by feelings of helplessness in the face of clinical, organization and societal demands, medical students are especially prone to moral distress (MD). Despite risks of disillusionment and burnout, efforts to support them have been limited by a dearth of data and understanding of MD in medical students. Yet, new data on how healthcare professionals confront difficult care situations suggest that MD could be better understood through the lens of the Ring Theory of Personhood (RToP). A systematic scoping review (SSR) guided by the RToP is proposed to evaluate the present understanding of MD amongst medical students. METHODS: The Systematic Evidence-Based Approach (SEBA) is adopted to map prevailing accounts of MD in medical students. To enhance the transparency and reproducibility, the SEBA methodology employs a structured search approach, concurrent and independent thematic analysis and directed content analysis (Split Approach), the Jigsaw Perspective that combines complementary themes and categories, and the Funnelling Process that compares the results of the Jigsaw Perspective with tabulated summaries to ensure the accountability of these findings. The domains created guide the discussion. RESULTS: Two thousand six hundred seventy-one abstracts were identified from eight databases, 316 articles were reviewed, and 20 articles were included. The four domains identified include definitions, sources, recognition and, interventions for MD. CONCLUSIONS: MD in medical students may be explained as conflicts between the values, duties, and principles contained within the different aspects of their identity. These conflicts which are characterised as disharmony (within) and dyssynchrony (between) the rings of RToP underline the need for personalised and longitudinal evaluations and support of medical students throughout their training. This longitudinal oversight and support should be supported by the host organization that must also ensure access to trained faculty, a nurturing and safe environment for medical students to facilitate speak-up culture, anonymous reporting, feedback opportunities and supplementing positive role modelling and mentoring within the training program.

Effects of Lisdexamfetamine, a Prodrug of D-Amphetamine, on Locomotion, Spatial Cognitive Processing and Neurochemical Profiles in Rats: A Comparison With Immediate-Release Amphetamine.

D-amphetamine has been used to enhance cognitive performance over the last few decades. Due to the rapid absorption after administration, d-amphetamine shows narrow effective window and severe abuse potential. Lisdexamfetamine, a prodrug of d-amphetamine, reduces the magnitude of plasma d-amphetamine concentration and prolongs the action duration when compared with immediate-release d-amphetamine at equimolar doses. However, the differences of these two drugs, which produce distinct pharmacokinetic characteristics, in cognition improvement still unclear. In present study, we compared the effects of d-amphetamine (i.p) and lisdexamfetamine (p.o) at equimolar doses (0.2, 0.5, 1.5, 4.5, and 13.5 mg/kg of d-amphetamine base) on locomotion, spatial working memory and recognition memory in rats. Given the crucial involvement of dopamine neurotransmitter system within the medial prefrontal cortex (mPFC) in cognitive processing, microdialysis was conducted to profile the difference in neurochemical characteristics between the two drugs. In our results, d-amphetamine ranges from 0.5 to 1.5 mg/kg significantly increased locomotor activity. However, d-amphetamine ranges from 0.2 to 13.5 mg/kg failed to improve spatial working memory and recognition memory in Y-maze-based spontaneous alternation and two-trial delayed alternation tasks of rats, respectively. In contrast, lisdexamfetamine with 4.5 mg/kg significantly increased the locomotion and improved both spatial working and recognition memory. Further, microdialysis showed that lisdexamfetamine induced lower magnitude and longer duration of extracellular dopamine increase than that of d-amphetamine. These results suggest that lisdexamfetamine was more effective than d-amphetamine in improving spatial cognitive performance, which was attributed to the steady and lasting dopamine release pattern within the mPFC.

Reduced Neutralization of SARS-CoV-2 Omicron Variant in Sera from SARS-CoV-1 Survivors after 3-dose of Vaccination

Recent studies found that Omicron variant escapes vaccine-elicited immunity. Interestingly, potent cross-clade pan-sarbecovirus neutralizing antibodies were found in survivors of the infection by SARS-CoV-1 after BNT162b2 mRNA vaccination (N Engl J Med. 2021 Oct 7;385(15):1401-1406). These pan-sarbecovirus neutralizing antibodies were observed to efficiently neutralize the infection driven by the S protein from both SARS-CoV and multiple SARS-CoV-2 variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta). However, whether these cross-reactive antibodies could neutralize the Omicron variant is still unknown. Based on the data collected from a cohort of SARS-CoV-1 survivors received 3-dose of immunization, our studies reported herein showed that a high level of neutralizing antibodies against both SARS-CoV-1 and SARS-CoV-2 were elicited by a 3rd-dose of booster vaccination of protein subunit vaccine ZF2001. However, a dramatically reduced neutralization of SARS-CoV-2 Omicron Variant (B.1.1.529) is observed in sera from these SARS-CoV-1 survivors received 3-dose of Vaccination. Our results indicates that the rapid development of pan-variant adapted vaccines is warranted.

Systematic scoping review on moral distress among physicians.

BACKGROUND: Concepts of moral distress (MD) among physicians have evolved and extend beyond the notion of psychological distress caused by being in a situation in which one is constrained from acting on what one knows to be right. With many accounts involving complex personal, professional, legal, ethical and moral issues, we propose a review of current understanding of MD among physicians. METHODS: A systematic evidence-based approach guided systematic scoping review is proposed to map the current concepts of MD among physicians published in PubMed, Embase, PsycINFO, Web of Science, SCOPUS, ERIC and Google Scholar databases. Concurrent and independent thematic and direct content analysis (split approach) was conducted on included articles to enhance the reliability and transparency of the process. The themes and categories identified were combined using the jigsaw perspective to create domains that form the framework of the discussion that follows. RESULTS: A total of 30 156 abstracts were identified, 2473 full-text articles were reviewed and 128 articles were included. The five domains identified were as follows: (1) current concepts, (2) risk factors, (3) impact, (4) tools and (5) interventions. CONCLUSIONS: Initial reviews suggest that MD involves conflicts within a physician's personal beliefs, values and principles (personal constructs) caused by personal, ethical, moral, contextual, professional and sociocultural factors. How these experiences are processed and reflected on and then integrated into the physician's personal constructs impacts their self-concepts of personhood and identity and can result in MD. The ring theory of personhood facilitates an appreciation of how new experiences create dissonance and resonance within personal constructs. These insights allow the forwarding of a new broader concept of MD and a personalised approach to assessing and treating MD. While further studies are required to test these findings, they offer a personalised means of supporting a physician's MD and preventing burn-out.

[Epidemiological and clinicopathological characteristics of prostate cancer in Hunan].

OBJECTIVE: To investigate the epidemiological and clinicopathological characteristics of PCa and provide some strategies for the clinical prevention and treatment of the malignancy. METHODS: This study included 1 594 cases of pathologically diagnosed PCa after radical prostatectomy in Xiangya Hospital of Central South University from January 1, 2010 to December 31, 2020. We collected the basic information about the patients, their main complaints and clinicopathological results, and analyzed the epidemiological and clinicopathological data. RESULTS: The patients were aged from 28 to 93 years, and the number of PCa cases showed an overall upward trend from 2010 to 2020. Urinary system symptoms were most common (62.53%) as initial symptoms, followed by increased PSA (17.82%), PCa, prostate nodule, prostate mass (8.43%) and bone metastasis (2.94%) found at physical examinations, and the cases of PSA elevation among the clinic visitors increased year by year from 2010 to 2020. Gleason score 7 was found in a largest proportion of the PCa patients, and adenocarcinoma was the main pathological type (78.6%). Logistic regression analysis showed that high Gleason score, instead of age and expressions of Ki67, AR and ERG, was an independent risk factor for intraductal carcinoma. CONCLUSION: The incidence of PCa shows an increasing trend, and is more common in those over 50 years old. PSA screening is gradually popularized in China. Intraductal carcinoma, as a major risk factor for aggressive PCa and poor prognosis of the malignancy, is significantly correlated with high Gleason scores.

Cap-assisted endoscopic sclerotherapy and procedure for prolapse and hemorrhoids for internal hemorrhoids: a randomized controlled study / 中华消化内镜杂志

Objective:To compare the efficacy and safety of cap-assisted endoscopic sclerotherapy (CAES) and procedure for prolapse and hemorrhoids (PPH) for internal hemorrhoids.Methods:This study was a prospective double-blind controlled clinical one. A total of 80 patients with internal hemorrhoids who visited Baoding No.1 Central Hospital from March 2018 to March 2020 and met the inclusion and did not meet exclusion criteria, were randomly divided into CAES group ( n=40) and PPH group ( n=40) by random number table method, and received corresponding treatment respectively. The perioperative indices of the two groups were compared, including intraoperative blood loss, operation time, visual analogue scale (VAS) score at 24 and 48 hours after operation, length of hospital stay, treatment costs, time to return to normal life, and curative rates. The complications within 3 months after operation and the 1-year recurrence after operation were also compared between the two groups. Results:The operation was successfully completed in all patients. The intraoperative blood loss (0.54±0.15 mL VS 7.32±2.17 mL) and treatment cost (6 249.53±435.67 yuan VS 7 832.96±526.74 yuan) in CAES group were significantly lower than those in PPH group ( t=19.714, P<0.05; t=14.650, P<0.05). The length of hospital stay (3.53±0.94 d VS 5.18±1.36 d) and time to return to normal life (5.26±1.28 d VS 7.17±2.09 d) in CAES group were significantly lower than those in PPH group ( t=6.312, P<0.05; t=4.929, P<0.05). There was no significant difference in operation time between the two groups ( t=0.977, P>0.05). The VAS scores at 24 h (2.64±0.70 points VS 3.59±0.93 points) and 48 h (1.28±0.31 points VS 2.16±0.57 points) after operation in CAES group were significantly lower than those in PPH group ( t=5.162, P<0.05; t=8.578, P<0.05). There was no significant difference in the curative rate [90.0% (36/40) VS 97.5% (39/40)] between CAES group and PPH group ( χ2=0.853, P=0.356). During the follow-up period within 3 months after the operation, the incidence of urinary retention [0.0% (0/40) VS 15.0% (6/40)] and pain [2.5% (1/40) VS 22.5% (9/40)] in CAES group was significantly lower than those in PPH group ( χ2=4.504, P<0.05; χ2=7.314, P<0.05). No other complications occurred in the 80 patients. After 1 year of follow-up, the recurrence rate of CAES group was 7.5% (3/40), which was not statistically different from that in PPH group [5.0% (2/40), χ2=0.180, P>0.05]. Conclusion:As a new minimally invasive technique for the treatment of internal hemorrhoids, CAES has similar curative rate and 1-year recurrence rate to PPH. Compared with PPH, CAES shows the advantages of less trauma, less pain, faster recovery and lower cost.

SPECT/CT imaging of tumor-infiltrating CD8 + T cell to predict the efficacy of anti-PD-1 immunotherapy in mice / 中华核医学与分子影像杂志

Objective:To prepare 99Tc m-hydrazinonicotinamide(HYNIC)-αCD8/Fab ( 99Tc m-αCD8/Fab), and explore the predictive value of 99Tc m-αCD8/Fab SPECT/CT imaging for the efficacy of anti-programmed death-1 (PD-1) immunotherapy. Methods:The αCD8/Fab was modified with HYNIC- N-hydroxysuccinimide (NHS) and IRDye800-NHS to form HYNIC-αCD8/Fab and IRDye800-αCD8/Fab (Dye-αCD8/Fab), respectively. 99Tc m-αCD8/Fab was prepared in sodium bicarbonate buffer (pH=8.5), with SnCl 2 being used as the reducing agent. The labeling yield and radiochemical purity of 99Tc m-αCD8/Fab and its stability in PBS and fetal bovine serum (FBS) were tested in vitro. The mouse spleen and human peripheral blood lymphocytes were isolated for cell-specific binding and blocking experiments of 99Tc m-αCD8/Fab in vitro. SPECT/CT imaging was used to analyze the specific binding ability of the 99Tc m-αCD8/Fab probe in CT26 colon cancer mouse models (BALB/c). The near infrared fluorescence imaging and SPECT/CT imaging were performed to detect the intra-tumoral CD8 + T cell infiltration after anti-PD-1 therapy in tumor bearing mice, and the results were further verified by HE and immunofluorescence staining. CD8 + T cell depletion study was performed to determine the role of CD8 + T cells in the tumor responses to anti-PD-1 therapy. Two-way analysis of variance was used to compare the data difference. Results:The labeling yield of 99Tc m-αCD8/Fab was 90% with a high radiochemical purity (95%) and good stability in vitro (radiochemical purity still more than 80% after 720 min in PBS and FBS). 99Tc m-αCD8/Fab could specifically bind to mouse CD8 + T cells ((10.30±0.81) percent added radioactive dose (%AD)/10 6 cells), compared with the binding ability in human peripheral blood lymphocytes group and CD8 antibody blocking group ((1.78±0.61) and (1.59±0.25) %AD/10 6 cells; F=10.07, P<0.001). SPECT/CT imaging showed that 99Tc m-αCD8/Fab had markedly higher tumor uptake in the CT26 colon cancer mouse models. Near-infrared fluorescence imaging showed that the tumor uptake of 99Tc m-αCD8/Fab in the responsive group was significantly higher than in the nonresponsive group after anti-PD-1 treatment ((8.9±1.1)% vs (7.1±0.8)%; F=4.69, P=0.024), and SPECT/CT imaging found the similar result. HE and immunofluorescence staining of tumor and lymph nodes showed that the proportion of lymphocyte infiltration was higher in the responsive group. Furthermore, CD8 + T cell depletion significantly reversed the therapeutic effect of anti-PD-1 immunotherapy in tumor-bearing mice. Conclusions:In this study, 99Tc m-αCD8/Fab was successfully obtained. CD8-specific SPECT imaging could sensitively visualize the tumor-infiltrating CD8 + T cells, suggesting the potential application value to predict and evaluate the efficacy of immunotherapy in the clinical settings.

Expression and clinical significance of minichromosome maintenance protein 3(MCM3) in gastric cancer tissues / 国际生物医学工程杂志

Objective:To study the expression level and clinical significance of minichromosome maintenance protein 3(MCM3) in human gastric cancer.Methods:The expression levels of MCM3 mRNA and protein in gastric cancer and adjacent normal tissues were analyzed using public databases such as TCGA, CCLE and HPA. The clinicopathological features of 69 patients with gastric cancer were retrospectively analyzed, and the expression levels of MCM3 protein in tumor tissues and adjacent normal tissues were detected by immunohistochemical staining, and the relationship between it and clinicopathological features was analyzed. The interaction network of MCM3 proteins was analyzed using the STRING database.Results:The expression levels of MCM3 mRNA and protein in gastric cancer tissues were significantly higher than those in adjacent normal tissues ( P<0.05), and its high expression was correlated with the size of gastric cancer tumors ( P<0.05). In gastric cancer tissue, the expression of MCM3 was correlated with the expression level of proliferating cell nuclear antigen (PCNA) ( R=0.61, P<0.01), and there may be a protein-protein interaction. Conclusions:MCM3 plays an important role in gastric cancer by interacting with PCNA, and it is expected to become a new diagnostic and therapeutic target.