Palliative care is a way to help end-of-life populations improve their quality of life， and its development in practice cannot be separated from the level of education in palliative care. At present， some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system， lack of medical students’ hospice knowledge； insufficient interdisciplinary teaching faculty， weak palliative care awareness of medical students； single teaching evaluation mode； weak palliative care practice teaching links. To this end， it is necessary to improve the palliative care curriculum system， explore rich and diverse teaching methods； strengthen interdisciplinary teaching and faculty development， enhancing the awareness of palliative care among medical students；establish a scientific and effective evaluation method， carry out multi-dimensional dynamic assessment； expand the palliative care practice teaching base， and accurately improve the practical skills of medical students in palliative care， and other countermeasures to improve the level of palliative care education， and to help the strategy of Healthy China.

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

Objective:To investigate the efficacy of percutaneous balloon compression (PBC) in the treatment of trigeminal neuralgia (TN) and the risk factors of postoperative recurrence.Methods:A retrospective case-control study was conducted to collect the clinical data of 200 TN patients admitted to Hebei General Hospital from February 2018 to February 2019. According to different treatment methods, the patients were divided into operation group ( n=150) and conservative group ( n=50). The operation group received PBC treatment, and the conservative group received conservative treatment. The clinical efficacy of the two groups was recorded, including total effective rate, VAS, quality of life score (physical function, health status, social function, mental health). Patients treated with PBC were followed up for 4 years, and were divided into relapse group ( n=23) and non-recurrence group ( n=127) according to postoperative recurrence. The baseline data and laboratory indexes of the two groups were recorded, including fasting blood glucose, procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α). Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between groups. Chi-square test was used for comparison between count data groups. The factors related to postoperative recurrence of TN patients were first analyzed by univariate analysis, and then by multivariate Logistic regression analysis. A nomogram prediction model was constructed to predict postoperative recurrence, and its prediction efficiency was evaluated. The model was stratified by X-tile software to discuss its clinical application value. Results:The total effective rate, VAS of the operation group were 94.00%, 2.14±0.57, the conservative group were 78.00%, 3.87±1.16, and the difference between the two groups was statistically significant ( P< 0.05). The scores of physical function, health status, social function and mental health of quality of life in the operation group after treatment were 89.75±4.67, 90.36±5.68, 87.68±4.16, 88.79±5.09, the conservative group were 82.54±4.03, 84.67±4.28, 81.45±4.09, 80.69±4.89, and the difference between the two groups was statistically significant ( P< 0.05). Of 150 patients treated with PBC, 23 (15.33%) relapsed. Hypertension( OR=2.537, 95% CI: 1.069-6.019), diabetes( OR=5.179, 95% CI: 1.492-17.970), hyperlipidemia( OR=2.447, 95% CI: 1.227-4.883), CRP≥6.62 mg/L( OR=6.386, 95% CI: 1.738-9.854), IL-6≥19.55 ng/L( OR=8.028, 95% CI: 1.279-12.214), procalcitonin ≥1.13 ng/mL ( OR=7.615, 95% CI: 5.020-14.559), TNF-α≥4.56 ng/L( OR=6.226, 95% CI: 4.950-13.337) were independent risk factors for postoperative recurrence of PBC ( P<0.05). Based on the nomogram constructed by the above 7 risk factors, the decision curve showed that the net benefit rate was greater than 0 when the threshold probability was between 0.01 and 0.91. The X-tile software was used to divide the model into three levels of low (>21.6), medium (13.8-21.6) and high (<13.8) risk according to the Logistic risk score, and the postoperative recurrence probability of PBC was 10.87%, 20.74% and 64.04%, respectively. The recurrence rate of PBC in the high-risk group was significantly higher than that in the medium-risk group and the low-risk group ( χ2=5.136, P=0.015). Conclusions:Percutaneous balloon compression of trigeminal nerve in the treatment of patients with trigeminal neuralgia has the advantages of high total effective rate, fewer postoperative complications, good clinical efficacy, quick effect and so on. The construction of percutaneous balloon compression of trigeminal nerve in patients with trigeminal neuralgia postoperative recurrence risk prediction model to provide reference for clinical improvement of patient rehabilitation.

Objective:To investigate the role and mechanism of dopamine receptor D2(DRD2)in the immune microenvironment of breast cancer. Methods:The xenograft model of breast cancer is established using female C57BL/6J mice and murine breast cancer EO771 cells.Mice with transplanted tumor were treated by intraperitoneal injection of the specific antagonist of DRD2,thioridazine,while PBS was injected intraperitoneally in the control group.siDRD2 targeting DRD2 gene was intratumorally injected to tumor-bearing mice[negative control siRNA(siNC)was injected to the control group].The percentage of Ki-67 positive cells and CD4+T lymphocytes in tumor tissue was examined by immunohistochemical analysis.The proportion of CD45+CD4+T lymphocytes,CD45+CD4+IFNγ+Th1 cells and CD45+CD4+IL-1 7+Th17 cells was detected by flow cytometry. Results:Compared with the control group,the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)in tumor tissue were decreased in the thioridazine-treated group.The proportion of CD45+immune cells(P＜0.05)and CD4+T lymphocytes(P＜0.001)in thioridazine-treated group was higher than that in the control group.The proportion of Th1 cells(CD45+CD4+IFNγ+)increased(P＜0.001)in thioridazine-treated group.There was no significant changes in the proportion of Th1 7 cells(CD45+CD4+IL-1 7+)(P＞0.05).Compared with the control group(siNC),the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)were decreased in siDRD2 group.The proportion of tumor infiltrating CD4+T lymphocytes(P＜0.001)and Th1 cells(P＜0.001)in the siDRD2 group was higher than that in the siNC group,whereas the change in the proportion of Th1 7 cells was not statistically significant(P＞0.05). Conclusion:Down-regulation of DRD2 could promote the differentiation of Th1 cells and inhibit the proliferation of breast cancer cells in a mouse breast cancer model.

In the battle of COVID-19 epidemic prevention and control in China, the "countermarching people" faced up to all difficulties and went forward one after another to the forefront of anti-epidemic. Many vivid figures and examples have aroused our feelings and thoughts on life. Under the background of this special period, medical colleges should take the COVID-19 prevention and control as an opportunity to enrich the contents of bioethics education, blend in patriotism education, social responsibility education, medical moral education, and life and death culture education. By strengthening the construction of teaching staff, attaching importance to the integration of teaching contents, optimizing teaching carriers, expanding practical activities and recommending online teaching resources, the teaching reform of bioethics education is explored in order to enhance the effectiveness and sustainability of bioethics education and moral education.

Objective To study the stress distribution and biomechanical stability of the long-type composite locking plate already used in clinic practice and the novel short-type composite locking plate for treating Sanders type IIa, IIb and IIIab calcaneal fractures. Methods The three-dimensional (3D) models of Sanders type IIa, IIb and IIIab calcaneal fractures were established, and the force conditions of calcaneus in neutral standing position and under 20°dorsal extension were simulated. By referring to the physical form of human specimens, 500 N vertical axial load was applied, so as to study the displacement and relative displacement of the fracture block under the force, and the force conditions of bone tissues and internal fixation were analyzed. Results For Sanders type IIa, IIb calcaneal fractures treated with long-type and short-type composite locking plates, the stress concentration positions of the plates and calcaneal fractures were basically the same. The maximum stress difference of the two plates for fixing calcaneal fractures with the same type was smaller than 5 MPa, and there was no significant difference in the maximum displacement of the fracture models. For Sanders type IIIab calcaneal fractures treated with long-type and short-type composite locking plates, the maximum stress concentration occurred in the forearm of plate screws, indicating the risk of metal fatigue. The maximum stress difference was up to 12 MPa, and the maximum calcaneal displacement was up to 9 μm. Conclusions The long-type and short-type composite locking plates showed no significant differences in treating Sanders type IIa, IIb calcaneal fractures. For fixing Sanders type IIIab calcaneal fractures, the long-type composite locking plate was superior to the short-type composite locking plate.

Objective:To explore the application value of neurovascular three-dimensional (3D) reconstruction with 3D-slicer software in the preoperative diagnosis of neurovascular relations and offending arteries in patients with vertebrobasilar dilatation (VBD) complicated with facial muscle spasm (HFS).Methods:The clinical data of 42 patients with VBD complicated with HFS accepted microvascular decompression (MVD) in our hospital from January 2016 to February 2019 were retrospectively analyzed. The data of skull 3D-TOF MR angiography and 3D-FiESTA MR imaging were imported into 3D-slicer software to establish 3D models of the blood vessels, brain stem and facial auditory nerves of the patients before surgery. The neurovascular relations and offending arteries found during surgery were compared with those diagnosed by 3D-TOF MR angiography combined with 3D-FiESTA MR imaging and 3D models.Results:The consistencies of neurovascular relations and offending arteries found during surgery and those showed by 3D models were good ( Kappa=0.889, P=0.000; Kappa=0.869, P=0.000). The consistency of neurovascular relations showed by 3D models and those diagnosed by 3D-TOF MR angiography combined with 3D-FiESTA MR imaging was good( Kappa=0.809, P=0.000); there was no significant difference between the two methods in diagnosing neurovascular relations ( McNemar-Bowker=5.000, P=0.082). The consistency of offending arteries showed by 3D models and those diagnosed by 3D-TOF MR angiography combined with 3D-FiESTA MR imaging was poor ( Kappa=0.336, P=0.000); there was significant difference between the two methods in diagnosing offending arteries ( McNemar-Bowker=23.000, P=0.000). Conclusion:The 3D-slicer software is used to perform 3D simultaneous reconstruction of blood vessels, nerves and brain stem in the cerebellopontine angle, and the results are highly consistent with surgical findings; 3D-slicer software is more helpful than 3D-TOF MR angiography combined with 3D-FiESTA MR imaging in identification of offending arteries, surgical risk assessment and surgical strategy formulation in patients with VBD complicated with HFS.

Objective To understand the situation of iodine deficiency disorders and iodine nutrition of children in Yunnan Province after the implementation of new standard of salt iodine,and provide the basic data for prevention and control of iodine deficiency disorders.Methods Using multistage sampling method,Yunnan provincial evaluations for iodine deficiency disorders elimination were carried out.According to the comparative analysis of 2010 (pre-adjustment) and 2015 (post-adjustment) evaluation results,the changes of the median of salt iodine,the coverage rate of iodized salt,the qualified rate of iodized salt,the rate of qualified iodized salt consumption,goiter rate of school children aged 8-10 and the median of urinary iodine were evaluated.Salt iodine was tested using the "Salt Industry General Test Method for Determination of Iodine" (GB/T 13025.7-1999);thyroid volume examination of children using B-scan ultrasonography,thyroid volume calculation and enlargement judgment using "Diagnostic Criteria for Endemic Goiter" (WS 276-2007);and urinary iodine detection using "Urinary Iodine Arsenic Cerium Catalytic Spectrophotometry" (WS/T 107-2006).Results The medians of salt iodine in 2010 and 2015 were 30.6 and 22.4 mg/kg,respectively,the difference was statistically significant (U =317 503.50,P ＜ 0.01).The coverage rates of iodized salt in 2010 and 2015 were 99.6％ (1 681/1 688) and 98.9％ (2 592/2 622),the qualified rates of iodized salt were 98.6％ (1 657/1 681) and 89.7％ (2 325/2 592),and the rates of qualified iodized salt consumption were 98.2％ (1 657/1 688) and 88.7％ (2 325/2 622),and the differences were statistically significant (x2 =6.42,125.11,130.18,P ＜ 0.01);the rates of children goiter in 2010 and 2015 were 0.8％ (25/3 272) and 1.4％(44/3 245),respectively;the medians of urinary iodine of children were 289.0 and 157.3 μg/L,respectively,the difference was statistically significant (U =1 121 669.50,P ＜ 0.01).Conclusion After decreasing of salt iodine level starting from 2012 in Yunnan Province,the children iodine nutrition condition is in a more proper level.

OBJECTIVETo explore the molecular basis for three pedigrees affected with hypophosphatemia vitamin D resistant rickets (X-linked hypophosphatemia, XLH).

METHODSPeripheral blood samples from the three pedigrees were collected. Following DNA extraction, the 11 exons and flanking regions of the PHEX gene were subjected to PCR amplification and direct sequencing. Pathogenicity of identified mutations was evaluated through genotype-phenotype correlation.

RESULTSFor pedigrees 1 and 2, pathogenic mutations were respectively identified in exon 8 (c.871C>T, p.R291X) and exon 15 (c.1601C>T, p.P534L) of the PHEX gene. For pedigree 3, a novel mutation (c.1234delA, p.S412Vfs*12) was found in exon 11 of the PHEX gene, which caused shift the reading frame and premature termination of protein translation.

CONCLUSIONThe three mutations probably account for the XLH in the affected pedigrees. The discovery of novel mutations has enriched the spectrum of PHEX gene mutations.

OBJECTIVETo detect potential mutations in two neonates suspected for Cornelia de Lange syndrome (CdLS).

METHODSPeripheral blood samples from the neonates and their parents were collected and analyzed for CdLS-related genes using targeted sequence capture and next-generation sequencing. Suspected mutations were confirmed by direct Sanger sequencing.

RESULTSThe neonates were found to respectively carry mutations c.7219C to T and p.D2339Lfs*4 of the NIPBL gene, among which the p.D2339Lfs*4 mutation has not been reported previously. No pathogenic mutation was found in other CdLS-related genes including NIPBL, SMC1A, SMC3, RAD21 and HDAC8.

CONCLUSIONThe c.7219C to T and p.D2339Lfs*4 mutations of the NIPBL gene probably account for the disease in both patients.