With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To evaluate the nutritional status of patients with decompensated liver cirrhosis and explore the correlation with malnutrition and the risk factors of depressed mood.Methods:190 cirrhotic patients admitted to the Department of Gastroenterology of the First Hospital of Shanxi Medical University from June to September 2023 were selected according to the inclusion and exclusion criteria. Eligible patients were divided into subgroups based on the presence or absence of malnutrition as determined by subjective global assessment (SGA). The Center for Epidemiological Studies Depression (CES-D) scale was used to assess patients' propensity for depressed mood. Relevant clinical data were also collected and analyzed.Results:A total of 185 patients were included, of which 126 were in the non-malnutrition group and 59 malnutrition group. There were significant between-group differences in terms of CES-D results, age, body mass index, platelets, D-dimer, serum sodium, third lumbar skeletal muscle index, grip strength, triceps skinfold thickness, and upper arm muscle circumference (all P<0.05). Correlation analysis showed that grip strength, triceps skinfold thickness, upper arm muscle circumference, serum sodium, and depressed mood tendency status were correlated with the development of cirrhotic malnutrition ( P<0.05). The diagnostic model for malnutrition in cirrhosis using these five indicators showed the area under the curve of 81.9%. Conclusions:Depression is closely related to the development of malnutrition in patients with liver cirrhosis. Independent risk factors for malnutrition in cirrhosis include serum sodium≤135 mmol/L, grip strength, triceps skinfold thickness, lower-than-normal upper arm circumference , and the tendency of depression , which demonstrate the combined contribution to the diagnosis of malnutrition in cirrhosis.

  Objective  To analyze the current status of the development of adaptation guidelines in China, as well as their methodological quality and the reporting quality, in order to provide reference for the development of adaptation guidelines.  Methods  We searched and collected adaptation guidelines led by Chinese researchers or institutions from 2015 to 2023 from four electronic databases, China National Knowledge Infrastructure, WanFang Data Knowledge Service Platform, SinoMed and PubMed, extracted the basic information of the adapted guidelines, and assessed their methodological quality and reporting quality using the Appraisal of Guidelines for REsearch and Evaluation (AGREE) Ⅱ and RIGHT-Ad@pt tools.  Results  A total of 14 adaptation guidelines were included, mainly focusing on nursing (42.9%, 6/14), with the most frequently used adaptation method of ADAPTE (71.4%, 10/14), and with reference to pre-existing guidelines mainly from the United States, the United Kingdom, and international organizations. Assessment by the AGREE Ⅱ tool showed that the average methodological quality score of the adapted guidelines was 36.6%. The scores were relatively high in the domains of clarity of expression and rigor of formulation (44.4% and 54.9%), and lowest in the domain of applicability (15.3%). The results of the RIGHT-Ad@pt tool showed that the reporting quality of the adaptation guidelines was relatively good, with the highest reporting rate of 91.2% and the lowest of 35.3%, and the reporting rates of seven articles were higher than 70%.  Conclusions  Adaptation guidelines in China are still in their infancy, with a relatively small number and mainly focusing on the nursing field. The most commonly used adaptation method is the ADAPTE method. The methodological quality and reporting quality of adaptation guidelines need to be further improved, and more research should be conducted on the specific conditions and timing of adaptation guidelines development.

Aim To explore the effect of quercetin(Que)on ferroptosis and the potential mechanisms in an Erastin-induced ferroptosis model in chondrocytes.Methods A model of Erastin-induced ferroptosis was established in C28/I2 chondrocytes.Cells were treated with different concentrations of Que.Cell viability and cytotoxicity were assessed by MTT and LDH assays.The expression levels of Prdx6 and ferroptosis-related proteins ACSL4 and GPX4 in chondrocytes were deter-mined by Western blot.Lipid ROS production in chon-drocytes was measured by flow cytometry,while the changes in mitochondrial membrane potential were de-tected by RH123 staining.Prdx6 mRNA expression in chondrocytes was quantified by RT-qPCR.The chan-ges in the expression of the ferroptosis-related proteins ACSL4 and GPX4 were detected by immunofluores-cence staining.Results Compared to the Erastin-in-duced ferroptosis model group,Que significantly im-proved the viability of C28/I2 chondrocytes and re-duced cell cytotoxicity.It decreased the expression of the ferroptosis-related protein ACSL4 and increased the expression of GPX4.Que also inhibited the production of lipid ROS in chondrocytes and strengthened their mitochondrial membrane potential.In addition,the ex-pression of Prdx6 was significantly reduced in the Eras-tin group compared to the control group,while Que treatment upregulated the expression of Prdx6.Mean-while,the inhibitory effect of Que on chondrocyte fer-roptosis was reduced by the use of MJ33,an inhibitor of Prdx6.Conclusion Que can inhibit Erastin-induced ferroptosis of C28/I2 chondrocytes,possibly by upregu-lating Prdx6,and thus play a protective role in chon-drocytes.

Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.

Objective To enhance the triage efficiency of patients with acute heart failure(AHF)by improving emergency severity index(ESI)score,and to achieve stratified care for patients with AHF.Additionally,the aim is to improve the combination of stratified scores and nursing care in emergency departments to address the limitations of current studies.Methods A retrospective nested cohort study was conducted on 120 patients with AHF admitted to the Affiliated Hospital of Guizhou Medical University from January 1,2019 to December 30,2021.According to the clinical outcomes of the patients,the patients were divided into subgroup A(71 cases,recovered after treatment,no serious complications during treatment),subgroup B[35 cases,discharged after treatment,multiple organ dysfunction syndrome(MODS),acute respiratory distress syndrome(ARDS),shock and other serious complications occurred during treatment],and subgroup C(14 cases,cardiac death during treatment).A prospective randomized controlled study involving 106 patients with AHF admitted to our hospital from January 1 to December 30,2022,was conducted,and the patients were divided into control group(53 cases)and stratified care group(53 cases)according to the random number table method.The control group received routine nursing care,while patients in the stratified care group received stratified care based on the ESI scoring clinical care pathway.The early warning score model of elderly patients with AHF was constructed with risk threshold as warning signal.The improved ESI scoring criteria were used to score AHF patients,with a total score of 25 points.The higher the score,the higher the risk.0-10 is divided into Ⅰ level risk,>10-20 is divided into Ⅱ level risk,>20 is divided into Ⅲ level risk.Implement nuring at grades Ⅲ,Ⅱ,and Ⅰ,respectively.The changes of modified ESI scores in subgroup A,subgroup B and subgroup C were observed,and Spearman correlation coefficient was used to evaluate the correlation between modified ESI scores and clinical outcomes of different severity of disease.Receiver operator characteristic curve(ROC curve)was drawn to evaluate the effectiveness of the risk threshold classification method of different nursing plan designs in the stratified nursing group and the control group,and to compare the efficiency differences of emergency nursing rescue time,rescue success rate,and stay time in the emergency department,and the incidence of complications such as MODS,ARDS,shock and nursing satisfaction during treatment between the stratified nursing group and the control group.Results The modified ESI score in subgroup C was the highest,significantly higher than that in subgroup B and A(19.6±1.7 vs.17.8±1.5,15.3±1.3,all P<0.05).Spearman correlation analysis showed that the modified ESI score was significantly positively correlated with the occurrence of complications,the occurrence of cardiac death,and the recovery after treatment(r values were 0.623,0.635,0.322,P values were 0.004,0.003,0.012,respectively).Therefore,an improved ESI score has a certain early warning effect on complications and cardiac death of patients.ROC curve analysis showed that the area under the ROC curve(AUC)of routine care for stratified care was 0.710 and 0.620,and the 95％ confidence interval(95％ CI)was 0.620-0.750 and 0.580-0.690,respectively,with Pvalues of 0.023 and 0.034.It shows that the difference between the two nursing methods is significant,and further indicates that the risk threshold classification method designed in this study is effective.With the increase of risk,the rescue time and emergency stay time of the two groups were gradually extended,and the success rate of rescue was gradually decreased,the rescue time and emergency stay time of grade Ⅲ risk were the longest and the success rate of rescue was the lowest,and the rescue time and emergency stay time of the stratified nursing group were significantly shorter than those of the control group(minutes:59.6±6.3 vs.76.5±7.2 and 57.6±5.4 vs.68.2±7.1,both P<0.05),the success rate of rescue was significantly increased[(68.7±6.1)％ vs.(54.6±5.2)％,P<0.05],and the difference of rescue time between grade Ⅰ risk and grade Ⅲ risk was the largest.There were significant differences in the success rate of rescue and the duration of emergency stay in grade Ⅲ risk.The incidence of complications such as MODS,ARDS and shock in stratified care group was significantly lower than that in control group[incidence of MODS:13.2％(7/53)vs.18.9％(10/53),incidence of ARDS:15.1％(8/53)vs.22.6％(12/53),incidence of shock:13.2％(7/53)vs.20.8％(11/53),all P<0.05],satisfaction of patients with service attitude,operation technique,comfort and timeliness were significantly improved compared with the control group[service attitude:28.3％(15/53)vs.18.9％(10/53),operation technology:30.2％(16/53)vs.20.8％(11/53),comfort:32.1％(17/53)vs.24.5％(13/53),timeliness:32.1％(17/53)vs.24.5％(13/53),all P<0.05].Conclusion Based on the modified ESI score,early risk warning thresholds are divided and stratified nursing is conducted,which is beneficial for timely intervention in AHF,effectively ensuring the clinical nursing value of patients during the implementation of medical measures,and has broad application prospects.

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.
Cord Blood Stem Cell Transplantation ; Core Binding Factor Alpha 2 Subunit ; Graft vs Host Disease ; Humans ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; Oncogene Proteins, Fusion ; Peripheral Blood Stem Cell Transplantation ; RUNX1 Translocation Partner 1 Protein ; Transplantation Conditioning

To study the effect of serum containing Xihuang pill on the proliferation of human breast cancer cell lines MDA-MB-435 and MCF-7 and the gene and protein expressions of Bcl-2, Bax, TP53, in order to explore the effect and mechanism of Xihuang pill in resisting breast cancer. The serum of the rats was prepared by the method of MTT assay. The expressions of Bcl-2 and Bax were detected by RT-PCR. The serum levels of Bcl-2 and Bax and the mRNA expression of TP53 were detected by immunofluorescence. The rats with serum containing Xihuang pill could inhibit the proliferation of MDA-MB-435 cells and MCF-7 cells (<0.05). The serum containing Xihuang pill increased TP53 and Bax in MDA-MB-435 cells (<0.05), and the ratio of Bcl-2/Bax was decreased (<0.05). Meanwhile, the serum containing Xihuang pill could up-regulate the mRNA expression of Bax in MCF-7 cells and decrease the expression of Bcl (<0.05), but there was no significant difference between the expression of TP53mRNA and Bax protein expressions after the treatment of MCF-7 cells with Xihuang pill serum. Serum containing Xihuang pill can induce the apoptosis of human breast cancer cells, and the mechanism of estrogen receptor-negative breast cancer cell apoptosis may be induced by up-regulating the mRNA expression of TP53, which can induce the expression of Bax and promote the metastasis of Bax to mitochondria, and ultimately play the role of inducing apoptosis.

BACKGROUNDHow the transcriptional factors regulated the innate and adaptive immune system in pregnancy and pre-eclampsia are less understood. Nevertheless, what the plasma work in the development of this disease was not sure. The present study was design to evaluate what the transcriptional factors change in innate and adaptive immune system and what the plasma do in this filed.

METHODSPeripheral blood mononuclear cells (PBMC) from non-pregnant women (n = 18), women with clinically normal pregnancies (n = 23) and women with pre-eclampsia (n = 20) were separated from peripheral blood to isolate monocytes and T cells. The purity of monocytes and T cells were analysed by flow cytometry. Monocytes and T cells were stimulated in either lipopolysaccharides (LPS) or phorbol-myristate-acetate (PMA), respectively. Transcription Factor Arrays were used to screen the transcription factors of interest in comparing of different groups. PBMC were isolated from another 8 non-pregnant samples were co-incubated with different groups of plasma. Polymerase chain reaction (PCR) was performed using whole cell extractions of the samples.

RESULTSNuclear factor of activated T-cells-1 (NFAT-1), signal transducers and activators of transcription-1 (STAT-1) and activator protein-1 (AP-1) are up-regulated in monocytes in pregnancy and more so in pre-eclampsia. On the the contrary, NFAT-1, STAT-1 and AP-1 are down-regulated in T cells in pregnancy and more so in pre-eclampsia. A reduction was observed in interferon (IFN)-γ, interleukin (IL)-12 and IL-4 expression in T cells incubated with pre-eclamptic plasma. An elevation was observed in tumor necrosis factor (TNF)-α, IL-1 and IL-12 expression in monocytes incubated with pre-eclamptic plasma.

CONCLUSIONSInnate immunity is over activated and adaptive immunity is over suppressed in the development of pre-eclampsia. NFAT-1, STAT-1 and AP-1 might be the central transcription factors in the pathogenesis of pre-eclampsia. They induced some changes in plasma and "educate" the monocytes and T cells for relevant cytokine production. Successful completion of this study will enhance our understanding of pre-eclampsia and will discover new knowledge beyond pregnancy. The work will inform future therapies for the treatment of a wide range of condition such as transplantation immunology and a wide range of immune and inflammatory conditions.

Adult ; Female ; Humans ; Immunity, Innate ; physiology ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-4 ; metabolism ; Leukocytes, Mononuclear ; metabolism ; Male ; NFATC Transcription Factors ; genetics ; metabolism ; Pre-Eclampsia ; immunology ; metabolism ; Pregnancy ; STAT1 Transcription Factor ; genetics ; metabolism ; Transcription Factor AP-1 ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Young Adult