Afferent baroreflex failure(ABF)is a rare disease.It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medul-la.The recognized causes include trauma,surgery in related areas(radical neck tumor surgery,carotid endarterectomy),neck radiotherapy,brain stem stroke,tumor growth paraganglioma and hereditary diseases,among which the most common cause is extensive neck surgery or radiotherapy for neck cancer.The main manifestations are fluctuating hypertension,orthostatic hypotension,paroxysmal tachycardia and bradycardia.This case is a young man,whose main feature is blood pressure fluctuation,accom-panied by neurogenic orthostatic hypotension(nOH).After examination,the common causes of hyper-tension and nOH were ruled out.Combined with the previous neck radiotherapy and neck lymph node dissection,it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection,which was called ABF.At the same time,the patient was complicated with chronic hyponatremia.Com-bined with clinical and laboratory examination,the final consideration was caused by syndrome of in-appropriate antidiuretic hormone(SIADH).Baroreceptors controlled the secretion of heart rate,blood pres-sure and antidiuretic hormone through the mandatory"inhibition"signal.We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery,which leads to abnormal blood pres-sure regulation and nOH,while the function of inhibiting ADH secretion was weakened,resulting in higher ADH than normal level and mild hyponatremia.The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate,and to alleviate the on-set of symptomatic hypotension.At present,drug treatment is still controversial,and non-drug treatment may alleviate some patients'symptoms,but long-term effective treatment still needs further study.The incidence of ABF is not high,but it may lead to serious cardiovascular and cerebrovascular events,and the mechanism involved is extremely complicated,and there are few related studies.The reports of rele-vant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complica-tions.

Objective To investigate the distribution and antibiotic resistance profiles of the bacterial strains isolated from urine samples in a tertiary Traditional Chinese Medicine hospital in Shanghai in the 12-year period from 2010 through 2021 for better empirical antibiotic use in clinical practice.Methods The clinical data of patients with urinary tract infection,including the species and antibiotic resistance of the bacterial strains isolated from urine samples from January 2010 to December 2021 were retrospectively analyzed.Results A total of 5 231 nondupliate bacterial strains were isolated,among which E.coli was the most common(52.8％),followed by Enterococcus spp(19.1％)and Klebsiella spp(11.1％).Most of the urinary isolates(76.0％)were isolated from the elderly aged 60-89,and only 3.1％of the strains were isolated from the young people aged under 44.Most of the bacterial strains were isolated from female patients(75.8％),however,more P.aeruginosa and A.baumannii were isolated from male patients compared to female patients(55.3％vs 44.7％and 67.7％vs 32.3％).About 13.7％of the strains were collected from the Department of Nephrology,more than the strains from any other clincial department.In intensive care unit(ICU),the proportion of E.coli was the lowest,while the proportion of Enterococcus spp was the highest.Enterobacterales showed lower resistance raets to carbapenems,cephamycin,amikacin,cefepime,and β-lactam/β-lactamase inhibitor combinations.P.aeruginosa showed higher susceptibility rates to carbapenems,aminoglycosides and β-lactam/β-lactamase inhibitor combinations compared to A.baumannii(≥54.6％vs≤39.8％).Gram-positive cocci were highly sensitive to glycopeptide antibiotics.No SS.aureus or E.faecalis isolates were found resistant to vancomycin.About 2.7％of the E.faecium isolates were resistant to vancomycin.The prevalence of drug-resistant bacteria was the highest in elderly patients,and in the strains isolated from ICU and emergency department.Conclusions Compared with general hospitals,a high proportion of elderly patients were treated in this hospital.It should be more cautious in the treatment of patients with urinary tract infection.The major bacterial species isolated from urine were E.coli,Enterococcus,and K.pneumoniae.Empirical treatment should be prescribed considering patient age and gender as well as the species and distribution of pathogenic bacteria.Urine culture and antibiotic susceptibility testing should be performed proactively.Appropriate antimicrobial agents should be selected according to the results of antimicrobial susceptibility testing.Antimicrobial ressitance surveillance should also be strengthened.

Standardized training of specialists is an important part of medical education system. The training goal is to cultivate high-quality specialists with high clinical practice ability, teaching and scientific research ability. Based on the training practice of clinical, teaching and scientific research ability of the standardized training of cardiovascular specialists in Peking University Third Hospital, this paper discusses how to establish and improve the quality management system of cardiovascular specialist training, and introduces the training content, training methods, training organization and management, and training effect respectively, hoping to provide more practical basis for improving the quality of standardized training for cardiovascular specialists.

The existence of cancer stem cells is regarded as the major cause for therapeutic resistance and relapse of a variety of cancer types including hepatocellular carcinoma (HCC). However, the tracing of such a subpopulation in vivo has been challenging. We have previously demonstrated that the isoform 5 of the voltage-gated calcium channel α2δ1 subunit, which can be recognized specifically by a monoclonal antibody 1B50-1, is a bona fide surface marker for HCC stem cells. Here we developed a strategy for optical imaging of α2δ1-positive cells by using a fusion protein containing the single chain variable fragment (scFv) of Mab1B50-1 and the luciferase NanoLuc which was tagged with Flag in the C-terminal. The scFv of Mab1B50-1 was fused to the N-terminal of NanoLucFlag using overlap PCR, and the recombinant fragment, which was named as 1B50-1scFv-NanoLucFlag, was subsequently cloned into a eukaryotic expression vector. The resulting construct was transfected into FreeStyle 293F cells in suspension using PEI reagent. The expression of the fusion protein was identified as a protein with molecular weight about 50 kDa by Western blotting. After purification by ANTI-FLAG® M2 affinity chromatography, 1B50-1scFv-NanoLucFlag was demonstrated to bind to α2δ1 positive cells specifically with a Kd value of (18.62±1.84) nmol/L. Furthermore, a strong luciferase activity of 1B50-1scFv-NanoLucFlag was detected in α2δ1 positive cells following incubation with the fusion protein, indicating that the presence of α2δ1 could be quantified using this fusion protein. Hence, 1B50-1scFv-NanoLucFlag provides a potential tool for optical imaging of α2δ1 positive cancer stem cells both in vitro and in vivo.
Carcinoma, Hepatocellular ; Humans ; Liver Neoplasms ; Neoplastic Stem Cells ; Recombinant Proteins/genetics* ; Single-Chain Antibodies/genetics*

Standardized training for specialist is recognized as the growth pathway to clinical medical experts worldwide. The United States has established a comprehensive specialist training system with a detailed assessment and evaluation system. This article introduces the evaluation tools of competency-oriented nephrology specialist training in the United States, including milestones evaluation system and EPAs (entrustable professional activities), which is of great significance for improving the evaluation tools of specialist training in China.

Objective:To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening.Methods:The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children′s public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated.Results:A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area ( P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area ( P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area ( P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area ( P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area ( P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area ( P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions:The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.

Objective:To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening.Methods:The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children′s public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated.Results:A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area ( P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area ( P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area ( P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area ( P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area ( P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area ( P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions:The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.

The national outbreak of coronavirus disease 2019 (COVID-19) has brought a severe challenge to the management of standardized residency training (SRT). To protect SRT residents from being infected by 2019 novel coronavirus (2019-nCoV), to guarantee the training program well carried out, and to prevent psychological health problems are conundrums to the management of SRT. In this article, the specific countermeasures are introduced from the following aspects: perfecting the management system, implementing quarantine and life support, conducting epidemic prevention and control training, turning training patterns suitable to epidemic prevention, and maintaining the psychological health of the residents. And we expect to provide references for SRT management under the public health emergency in the future.

Objective To observe the effect of stress on the rapid component of delayed rectifier potassium current (IKr) in rat cardiomyocytes. Methods Forty male SD rats were randomly divided into four groups (10 each): control group (Ctrl), exhaustive group (ES), noise group (WN) and composite group (ES+WN). Stress animal models were prepared as follows: Rats in ES group were undergoing exhaustive swimming as the stress factor, in WN group undergoing white noise and in ES+WN group undergoing exhaustive swimming + white noise as the stress factor. Langendorff device was used to reversely perfuse collagenase for isolating the rat's ventricular myocytes. The effect of stress on IKr current and gating mechanism of single ventricular myocyte was recorded by whole-cell patch clamp technique. Results Compared with the Ctrl group, the tail current density of IKr (IKr,tail) of ventricular myocytes increased significantly in ES group and WN group (P<0.01). The IKr,tail current density of the ventricular myocytes in ES+WN group was significantly higher than that in ES group and WN group (P<0.01), and the effect was voltage dependent. Gating mechanism revealed that the half inactivation voltage of IKr,tail (V1/2,inact) can be shifted to the right in ES group, WN group and ES+WN group when compared with the Ctrl group, and the recovery time constant shortened after inactivation (P<0.01). However, the steady-state activation, fast inactivation constant and voltage dependence of IKr,tail were not statistically significant in ES group, WN group and ES+WN group when compared with the Ctrl group. Conclusion Stress increases the IKr current in rat cardiomyocytes, suggesting it be one of the electrophysiological bases of stress-induced arrhythmia.