The red doctor spirit， as an essential component of the Chinese Communist Party’s red health culture， is deeply rooted in the historical fertile soil of revolutionary practice. It serves as a crucial spiritual force driving the development of China’s healthcare undertakings and the reform of medical education. Anchored in firm political belief and a noble professional mission， it follows a dual path of constructing medical ethics and promoting humanistic care， thereby laying a solid cultural foundation for the modern medical education system in China. Integrating the spirit of red medicine into the ideological and political education system for medical students helps guide them in strengthening their ideals and beliefs， fulfilling their professional mission of healing the wounded and rescuing the dying， cultivating a rigorous and pragmatic work style， and establishing a professional spirit of pursuing excellence. Through the dual advancement of ideological guidance and practical instruction， the professional sense of responsibility among medical students can be further enhanced， providing sustained spiritual momentum for the cultivation of medical talents in the new era and the implementation of the “healthy China” strategy.

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.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

OBJECTIVE：To explore th e applicatio n of team situatio nal simulation education and teaching mode in clinical pharmacy teaching. METHODS ：A total of 60 clinical pharmacy interns were selected as the research objects ，and course disease was type 2 diabetes mellitus. Thirty interns were randomly selected as control group ，using traditional teaching mode ；other 30 interns were selected as trial group ，which carried out team situational simulation education and teaching mode. The teaching effects were evaluated by using the satisfaction of interns to the two modes ，the comprehensive score of graduation examination and the self-evaluation of learning effect. RESULTS ：Compared with traditional teaching mode ，team situational simulation education and teaching mode was conducive to stimulate the learning interest of interns ，improve their interpersonal communication ability ， cultivate teamwork spirit ，improve the awareness of humanistic care ，and cultivate the professional attitude of clinical pharmacists （P＜0.05）. Compared with control group ，the comprehensive score of trial group was dominantly increased （P＜0.001），and the scores of professional quality ，humanistic care and communication skills in the trial group were significantly higher than control group（P＜0.01）. In terms of self-evaluation of learning effect ，except for the pathogenesis of type 2 diabetes and the commonly used treatment regimens ，the self-evaluation scores of the other items in trial group were significantly higher than control group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Team situational simulation education and teaching mode is superior to traditional teaching mode for clinical pharmacy teaching.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Inflammatory orofacial pain, in which substance P (SP) plays an important role, is closely related to the cross-talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs). SGC activation is emerging as the key mechanism underlying inflammatory pain through different signalling mechanisms, including glial fibrillary acidic protein (GFAP) activation, phosphorylation of mitogen-activated protein kinase (MAPK) signalling pathways, and cytokine upregulation. However, in the TG, the mechanism underlying SP-mediated orofacial pain generated by SGCs is largely unknown. In this study, we investigated whether SP is involved in inflammatory orofacial pain by upregulating interleukin (IL)-1β and tumour necrosis factor (TNF)-α from SGCs, and we explored whether MAPK signalling pathways mediate the pain process. In the present study, complete Freund's adjuvant (CFA) was injected into the whisker pad of rats to induce an inflammatory model in vivo. SP was administered to SGC cultures in vitro to confirm the effect of SP. Facial expression analysis showed that pre-injection of L703,606 (an NK-1 receptor antagonist), U0126 (an inhibitor of MAPK/extracellular signal-regulated kinase [ERK] kinase [MEK] 1/2), and SB203580 (an inhibitor of P38) into the TG to induce targeted prevention of the activation of the NK-1 receptor and the phosphorylation of MAPKs significantly suppressed CFA-induced inflammatory allodynia. In addition, SP promoted SGC activation, which was proven by increased GFAP, p-MAPKs, IL-1β and TNF-α in SGCs under inflammatory conditions. Moreover, the increase in IL-1β and TNF-α was suppressed by L703, 606, U0126 and SB203580 in vivo and in vitro. These present findings suggested that SP, released from TG neurons, activated SGCs through the ERK1/2 and P38 pathways and promoted the production of IL-1β and TNF-α from SGCs, contributing to inflammatory orofacial pain associated with peripheral sensitization.

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

Objective To explore the protective effect of erythropoietin(EPO) administrated by intranasal on cerebral ischemia reperfusion in rats with acute cerebral infarction reperfusion.Methods Total of 100 SD rats were divided into model control group,sham operation group,intraperitoneal administration group ([PEPO group),nasal saline group (INNS group) group,and nasal drug delivery group (INEPO group) with 20 in each group.The middle cerebral artery occlusion model of rat was established by thread embolism method and the NSS method was used to evaluate the neural behavior of rats.The expression of EPO in peripheral blood,cerebrospinal fluid and brain regions of rats were detected by Elisa.The vascular endothelial growth factor(VEGF) in brain was detected by immunofluorescence and then the density of newborn blood vessels in the brain was measured.Results Fifteen days after the operation,the NSS score of INEPO group(3.80± 1.61) was significantly lower than that of IPEPO group (11.53±2.11),and the difference was statistically significant(P＜0.01).And the levels of EPO in blood,cerebrospinal fluid and different brain regions of rats in INEPO group were higher than that of INNS group(all P＜0.01).Compared with IPE-PO group,the level of EPO cerebrospinal fluid and different brain regions of rats in INEPO group increased obviously,the difference was statistically significant (all P＜0.01),and the EPO concentration of the olfactory bulb was the most obvious (INEPO group:(1 456.90 ± 128.22) pg/ml,IPEPO group:(426.11 ± 36.68)pg/ml,P＜0.01).Seventy-two hours after operation,the expression of CD31 in ischemic penumbra of rats of model control group (18.21 ± 3.45),INNS group (18.54 ± 2.58),IPEPO group (27.01 ± 2.13) and INEPO group(35.52±2.79)was increased compared with sham operation group (5.14± 1.28),and the difference was statistically significant (all P＜0.05).The expression of CD31 in IPEPO group and INEPO group was significantly higher than that in INNS group (P＜0.05).In INEPO group,the expression of CD31 increased significantly compared with that of IPEPO group (P＜0.05).Conclusion Nasal administration of EPO can effectively improve the neurological function of rats with ischemia-reperfusion,and increase the expression of CD31 in the brain tissue of rats.The effect of nasal administration is better than that of intraperitoneal administration.

Objective To explore the effects of application calcitonin gene related peptide(CGRP) in cisterna magna on cerebral vasospasm after experimental subarachnoid hemorrhage (subarachnoid hemorrhage,SAH) in rat models.Methods 64 male Wistar rats were randomly divided into 4 groups.Group A was normal control group.After the subarachnoid hemorrhage models were established,group B,C,D were given normal saline,CGRP and adenovirus CGRP through cisterna magna respectively.White blood cells in cerebrospinal fluid were detected by automatic blood analyzer,CGRP activity was detected by enzyme linked immunosorbent assay,circulating endothelial cells were observed through laser scanning confocal microscope and parietal cortex regional cerebral blood flow were observed by laser doppler flowmeter.Basilar artery vasospasm and arterial blood gas analysis were detected by digital subtraction angiography and blood gas analyzer respectively.Results Before and after administration,there were no statistical differences in white blood cells and artery blood gas among the 4 groups (both P＞ 0.05).After administration 48 h,compared with group A,concentrations of CGRP in cerebrospinal fluid group B (0.006±0.002) did not increase (P＞0.05),but increased 200 times in Group C ((1.160±0.170) nmol/L,P＜0.05)and nearly 400 times in group D ((2.071±0.412) nmol/L,P＜0.05).Peripheral blood circulating endothelial cells count:after administration 48 h,group C((5.56±0.61) ind/0.9 μL) was less than in group B((9.94± 0.73) ind/0.9 μL).Group D((5.16±0.61) ind/0.9 μL) was less than group C(P＜0.01).Regional cerebral blood flow:after administration,compared with group B,cerebral blood flow of group C and group D increased,and the differences were both statistically significant (P＜0.01).Basilar artery diameter was detected after administration 12 h,group D ((1.000±0.025) mm) was 13％ bigger than group B ((0.670±0.028)mm,P＜0.05),3％ bigger than group C ((0.900±0.023) mm) (P＞0.05).Conclusion Cerebral vasospasm after SAH can be effectively improved by administration CGRP in cisterna magna.Adenovirus CGRP effect is better than CGRP.

Objective To summarize the clinical treatment experience of blood culture-negative infective endocarditis,and to explore the surgery chance and therapeutic strategy of blood culture-negative endocarditis. Methods One hundred and sixty-six patients who were diagnosed blood culture-negative endocarditis in the Aisa Heart Hospital of Wuhan from Jul. 2008 to Dec. 2012 were recruited in the study. Broad-spectrum antibiotics including cefuroxime axetil and levofloxacin were used before the result of blood culture,and sensitive antibiotics were selected to control patient's condition when getting the result of blood culture. But broad-spectrum antibiotics were continuously used to the blood culture-negative endocarditis until stable condition. When the conditions were stable,active preparation before surgery should be carried out. Thoroughly clear the vegetation and protect the cardiorespiratory function during operating. Kata-step antibiotics were used to control patient's condition until normal temperature,as well as the number of leukocytes decreased,blood sedimentation normalized and C-reaction protein decreased. Then,the narrow-spectrum antibiotics were selected including cephalosporin until discharged from hospital,and continued treatment of antibiotics for 4 - 6 weeks. Results Five patients died after the operation,including 1 case died of low cardiac output syndrome,2 cases died of multiple organ failure,1 case died of septicemia and the 1 case died of cerebral embolism. All the other patients discharged from hospital successfully. Conclusion The patients with blood culture-negative IE should be controlled rapidly. The duration and dose of antibiotics should be enough. Active operative preparation should be taken and then surgery timely. Thus,the hospital mortality could decrease and prompt the long-term outcome.