Objective:To construct an entrustable professional activities (EPAs) assessment framework for undergraduate medical students suited to the national conditions in China.Methods:The Delphi method was used to construct an EPAs assessment framework for medical undergraduates. Twenty-one clinical experts across China were invited to participate in two rounds of Delphi consultation.Results:All the 21 experts completed the two rounds of Delphi consultation. The effective questionnaire response rates of the two rounds of consultation were 100.0% (21/21). For the first-round expert consultation, the W values of importance and feasibility scores of EPAs were 0.182 and 0.173 (both P<0.05), respectively. For the second-round expert consultation, the W values of importance and feasibility scores of EPAs were 0.167 and 0.152 (both P<0.05), respectively. According to the second-round Delphi consultation, the importance and feasibility scores of all 14 EPAs indicators were >3.5 points, with the coefficients of variation <0.25 points. We preliminarily established 12 EPAs indicators and 42 key assessment points and determined the expected entrustment levels of each EPA at different stages for medical undergraduates. Conclusion:This study preliminarily constructed an EPAs assessment framework for medical undergraduates, which provides a new evaluation method for the cultivation of medical undergraduates in China.

Objective:To analyze the epidemic characteristics of Cornona virus disease 2019 (COVID-19) in Wangkui County, Heilongjiang Province, and to provide a reference for optimizing epidemic prevention and control strategies.Methods:The epidemic characteristics of COVID-19 in Wangkui County, Heilongjiang Province in January 2021 were analyzed by applying the national infectious disease report system and information management system of Heilongjiang Provincial Center for Disease Control and Prevention, the public health emergency report management information system, the epidemiological investigation report of the Heilongjiang Provincial Center for Disease Control and Prevention and Suihua Municipal Certer for Disease Control and Prevention, and the epidemic information publicly released by the Health Commission of Heilongjiang Province.Results:From January 9 to February 5, 2021, 804 cases infected with Cornona virus were reported in Wangkui County, with an infection rate of 280.29/100 000. The epidemic affected 20 districts and counties in 6 cities, including Suihua, Harbin, Mudanjiang, Qiqihar, Yichun and Daqing. The sex ratio of male to female was 1.08 ∶ 1.00 (418 ∶ 386), the age ranged from 3 months to 93 years old, and the median age was 50 years old. The proportion of confirmed cases and asymptomatic infection was 1.23 ∶ 1.00 (444 ∶ 360), there were significant differences in gender, age and occupation between them ( P < 0.05). There were 314 places where the aggregation epidemic occurred, with family aggregation as the main way (300 households, 95.54%). The places with the highert average number of cases were banquets (25.75 cases/place) and grocery stores/chess and card rooms (16.00 cases/place). Conclusions:In January 2021, the epidemic of COVID-19 in Wangkui County is a typical outbreak in rural areas of North China. The main reasons for the rapid spread of the epidemic are a large number of gathering activities, frequent contact of personnel in confined spaces and other factors.

Objective:To evaluate the effect of ionizing radiation on chromosome aberration of peripheral blood lymphocytes in children with vascular interventional procedure.Methods:The chromosome aberration of peripheral blood lymphocytes was analyzed before and after vascular interventional procedure to assess the effect of low-dose ionizing radiation on chromosomes. Peripheral blood (PB) was collected using heparin as an anticoagulant from 26 patients before and after (within 10 minutes) vascular interventional surgery. Informed consent was obtained from the patients′ parents.Results:Dicentric + centric ring (dic+ r) formation increased significantly ( U=647, P<0.01) in peripheral blood lymphocytes of children after interventional operation. No correlation was observed between the rate of dic+ r and the cumulative dose (CD), dose area product (DAP), age, body weight, gender and the estimated effective dose E ( P>0.05). There was no significant difference in dic+ r rate of children between different genders, ages and lesion sites ( P>0.05). The dic+ r rate after interventional operation exceeded 40×10 -3 in 4 of 26 cases with the highest of 95.83×10 -3. Conclusions:The ionizing radiation during children′s vascular interventional procedure might lead to the increase of chromosome aberration of peripheral blood lymphocytes and some children are abnormally sensitive. Great attention should be paid to the justification and radiation protection during interventional procedure for children.

Radiotherapy is one of the most commonly used and effective method to treat malignant tumors in clinical practice. However, there are still some limitations including high radiotherapy doses, harmful side effects on normal tissues, and radiation resistance of tumor cells. Therefore, seeking safe and effective radiotherapy sensitizers to improve radiation sensitivity of tumor cells has been focused for a long time. Histone deacetylase inhibitors (HDACIs), as a kind of epigenetic modifiers, can regulate the sensitivity of tumor cells to ionizing radiation and ultraviolet radiation in addition to the inherent anticancer characteristics. This article reviewed the molecular mechanisms of HDACIs in enhancing radiation sensitivity and by selectively killing tumor cells.

Endoplasmic reticulum stress (ERS) is an important defense mechanism. Under the stimulation of various physical and chemical factors, cells respond to a series of signal transduction pathways to determine whether cells are adapted or not. Fluoride can cause impairment to the nervous system of the body, leading to learning, memory and cognitive impairment, but its mechanism is unknown. Studies have shown that the mechanism of fluorosis damage may be related to ERS-mediated apoptosis. In recent years, nervous system injury caused by fluorosis has been widely concerned by researchers, and ERS may play an important role in its mechanism. Therefore, this article will comprehensively explain the possible role of ERS in nervous system injury caused by fluorosis, and provide a new idea for elucidating the pathogenesis of fluorosis.

Objective To detect the expression levels of insulin-like growth factor 1 (IGF-1) and leptin (LP) in serum of patients with colorectal cancer, and to analyze its clinical significance. Methods Seventy-three patients with colorectal cancer, 37 patients with benign colorectal cancer and 40 healthy subjects were enrolled. Serum IGF-1 and LP levels of all the subjects were measured. A two-year follow-up study of colorectal patients was performed to observe the occurrence of lymph node metastasis. Logistic regression was used to analyze the factors affecting lymph node metastasis in colorectal cancer patients. The area under the receiver operating characteristic curve (AUC) was used to analyze the diagnostic value of IGF-1 and LP for colorectal cancer and recurrence. Results The serum IGF-1 concentration in colorectal cancer was significantly lower than that in the control group (P<0.05), but there was no significant difference between the patients with benign lesions (P>0.05). The serum LP level of colorectal cancer was significantly higher than that of benign lesions and control group (P<0.05). Both IGF-1 and LP have certain diagnostic value for colorectal cancer, and the combined test and efficacy of the two methods are higher than those of the separate test (P<0.05). The two-year recurrence rate of colorectal cancer patients was 16.43％, and the patient age (≥40 years old), TNM grade (Ⅲ～Ⅳgrade), tumor diameter (≥4 cm), vascular infiltration and deep muscle infiltration in the recurrent patients were significantly higher than that in the untreated patients (all P<0.05). In the cancer metastasis patients, the level of serum IGF-1 and LP was significantly lower and higher than that in non-metastatic patients, respectively (all P<0.05). Vascular infiltration, deep myometrial invasion, low IGF-1 levels, and high LP levels were independent predictors of recurrence in colorectal cancer patients, and the combined predictive AUC of the above four factors was 0.956 (95％CI:0.9881～0.990). Conclusions In patients with colorectal cancer, IGF-1 level is low and LP level is high, which is closely related to cancer recurrence.

Objective: To investigate the association of D-dimer (DD) level on admission with the hospital length of stay (LOS) for the children with community-acquired pneumonia (CAP). Methods: The children diagnosed as CAP hospitalized in the Second Hospital of Tianjin Medical University from December 2016 to December 2017 were studied. The clinical and biological variables were retrieved via electronic medical record system. Binary logistic regression model and Cox proportional risk model were constructed to estimate the assosiation of DD level with hospital length of stay(LOS). Results: A total of 413 children met the inclusion criteria. Their median of LOS was 7 days (range from 3 to 21 days). The median of DD level on admission was 510.87 ng/mL and tertiles were 400 ng/mL and 712.23 ng/mL. In logistic regression model, both the high (＞712.23 ng/mL) and middle (400-712.23 ng/mL) DD level groups were in more risk for hospital stay of more than 7 days in comparison with the low DD level group (＜400). The OR values were 3.335 (95%CI:1.973-5.637, P＜0.001) and 2.015 (95%CI:1.195-3.398, P=0.009) respectively. Consistently, in Cox model high level of DD was associated with low probability of discharge (HR=0.652, 95%CI: 0.486-0.874, P=0.004 ), suggesting more risk of prolonged LOS in contrast to the low DD level group. Conclusion The DD level on admission should be independently associated with the hospital length of stay, suggesting the consideration of DD levels may be helpful for clinical management of the hospitalized children with CAP.

BACKGROUND/AIMS: To evaluate cellular immune function in systemic lupus erythematosus (SLE) patients over 60 years old, the association between antinuclear antibody (ANA) titers and the ratio of CD4⁺/CD8⁺ was analyzed in this study. The distribution of ANAs and extractable nuclear antibodies (ENAs) in a healthy elderly population was also investigated. METHODS: Serum ANA titers were assayed by indirect immunofluorescence (IIF) and the CD4⁺/CD8⁺ T-cell ratio was determined by flow cytometry in 76 SLE patients and 30 healthy control individuals. IIF of cytoplasm and nuclear and nucleolar staining were performed on samples taken from 286 healthy elderly individuals. ENA levels were determined using a strip enzyme immunoassay among patients that tested positive for ANAs. RESULTS: ANA titers were negative in the 30 control individuals, but were positive in the 76 SLE patients. Based on ANA titers, the SLE patients were stratified to low (≤ 1:320), medium (1:640 to 1:1,280), and high (≥ 1:2,560) titer groups. The average CD4⁺/CD8⁺ ratio of the SLE group was significantly lower than that of the control group. Among the 286 healthy elderly volunteers, 59 (20.63%) tested positive for ANAs. A homogeneous pattern was present in 47.46% of those 59 patients and a granule pattern in the karyoplasm was present in 33.90%. Furthermore, of the 59 patients, ENAs immunoassay was positive in 18 (30.51%); Sjogren syndrome-related antigen A (SSA)/52 kd and Sjogren syndrome antigen B (SSB)/La were the two major antibodies. CONCLUSIONS The significantly lower CD4⁺/CD8⁺ ratio among SLE patients over 60 years old is associated with deregulated immune responses and the development of SLE. A low ANA titer (1:160) is common in healthy elders, emphasizing the importance of considering age when determining if the evaluation of ANA titers is to be included in autoimmune disease diagnosis.

Objective To analyze the changes of endoplasmic reticulum stress (ERS) in the spleen of water-improving fluorosis rat,to explore the mechanism of fluoride-induced immune system damage,and to provide a scientific basis for prevention and control of endemic fluorosis.Methods Forty-eight male Wistar rats of SPF grade were randomly divided into control group and low,medium and high fluoride dose groups according to body mass (120-140 g),12 rats in each group.The sodium fluoride (NaF) content was 0,50,100 and 150 mg/L,respectively.The animals were allowed free access to water and food.After 12 weeks of fluoride exposure,6 rats in each group were selected to isolate the spleen;the remaining rats in each group were changed to drink distilled water containing no NaF,and the spleen was separated after 12 weeks of feeding.The levels of mRNA of glucoseregulated protein (GRP78),spliced X-box binding protein 1 (XBP1-s),activating transcription factor 4 (ATF4),homologous protein (CHOP) and cysteine containing aspartate specific protease 12 (Caspase-12) in spleen were determined by quantitative real-time PCR (qRT-PCR).Results Before the water-improving,the expressions of GRP78 (1.00 ± 0.09,1.69 ± 0.35,1.39 ± 0.29,1.19 ± 0.19),XBP1-s (1.00 ± 0.12,1.40 ± 0.23,1.24 ± 0.26,1.38 ± 0.11),ATF4 (1.00 ± 0.17,1.86 ± 0.56,2.33 ± 0.55,1.95 ± 0.74),CHOP (1.00 ± 0.53,2.84 ± 0.68,3.06 ± 1.29,2.50 ± 0.35) and Caspase-12(1.00 ± 0.12,1.90 ± 0.29,1.56 ± 0.35,1.76 ± 0.23) mRNA in the control group and low,medium and high fluoride dose groups were statistically significant (F =8.45,5.38,6.38,8.21,11.31,P ＜ 0.05).Except for the GRP78 in high fluoride dose group,the above indicators in fluoride groups were higher than the control group (P ＜ 0.05).After the water-improving,the expressions of GRP78 (1.00 ± 0.36,0.75 ± 0.13,0.98 ± 0.41,0.47 ± 0.19),XBP1-s (1.00 ± 0.25,0.70 ± 0.06,0.74 ± 0.17,0.65 ± 0.21),ATF4 (1.00 ± 0.51,0.66 ± 0.09,0.91 ± 0.34,0.81 ± 0.29),CHOP (1.00 ± 0.36,0.92 ± 0.12,0.84 ± 0.16,0.67 ± 0.20) and Caspase-12 (1.00 ± 0.45,0.65 ± 0.11,0.65 ± 0.25,0.51 ± 0.27) mRNA in the control group and low,medium and high fluoride dose groups were not statistically significant (P ＞ 0.05).Before and after the water-improving,the expressions of XBP1-s,ATF4,CHOP and Caspase-12 mRNA were statistically significant in fluoride groups (P ＜ 0.05),and the GRP78 only had a statistically significant difference in the low fluoride dose group (P ＜ 0.05).Conclusions Fluoride exposure causes ERS response in rat spleen,up-regulation of ERS-related gene expression,which is decreased after water-improving,and the ERS response is weakened.The water-improving may contribute to the recovery of fluoride-induced immune function damage.

Objective To study the effects of different fluoride concentrations on proliferation and apoptosis of rats' immune cells,and to explore the effects of fluoride on immune function.Methods Sixty male Wistar rats were randomly divided into four groups,and the concentrations of NaF in drinking water for each group (15 rats in each group) were 0,50,100,and 150 mg/L,respectively.They were freely fed water and commercial standard chow.All rats were sacrificed after 12 weeks.Thymus index was calculated.Lymphocyte proliferation activity in the blood was detected by Cell Counting Kit-8 assay.The apoptosis of monocytes in blood was detected by Annexin V/PI method.The apoptosis of lymphocytes in spleen and thymus was detected by Tunal method.Results After 12 weeks of fluoride exposure,the difference in the thymus immune organ index between the four dose groups was statistically significant (F =6.50,P ＜ 0.05);after 12 weeks,the thymus immune organ index of the low and middle dose groups was significantly lower than that of the control group (0.70 ± 0.19,0.84 ± 0.18 vs 1.16 ± 0.33,P ＜ 0.05).There were significant differences in B and T lymphocyte viability between the four dose groups (F =539.97,4.92,P ＜ 0.05).The viability of B lymphocyte in the blood of the middle dose group was significantly lower than those of control group and the low dose group [(58.09 ± 4.59)％ vs (100.00 ± 9.01)％,(106.70 ± 4.82)％,P ＜ 0.05].The viabilities of T lymphocyte in the blood of the low and middle dose groups were significantly lower than that of the control group [(81.11 ± 2.93)％,(75.68 ± 2.34)％ vs (100.00 ± 34.02)％,P ＜ 0.05].The apoptosis rates of blood mononuclear cells in the fluoride-treated groups were significantly increased than that of control group [(48.00 ± 7.45)％,(47.26± 5.94)％,(48.20 ± 3.40)％ vs (32.50 ± 13.70)％,P ＜ 0.05).Immunohistochemistry results showed that the number of apoptotic lymphocytes in the spleen and thymus increased significantly in high dose group.Conclusion Fluoride can reduce the thymus immune organ index of rats,affect the proliferation of lymphocytes in blood,thymus and spleen,and promote apoptosis of lymphocytes,thus affecting the immune function.