Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

A 40-year-old male patient was treated orally with carbamazepine 0.1 g once daily for epilepsy. Twenty days later, the patient developed fever without obvious cause (highest body temperature 39.0 ℃), which showed no improvement after treatments with ribavirin and ibuprofen. Eleven days later, splenomegaly occurred, and serum ferritin was elevated (1 188.18 μg/L). Etiological testing showed positive influenza virus A/B antibody but negative nucleic acid; tests of Epstein-Barr virus, cytomegalovirus, novel coronavirus, respiratory syncytial virus, adenovirus, human rhinovirus, Mycoplasma pneumoniae, Mycobacterium tuberculosis, Leishmania donovani, Brucella, and Toxoplasma gondii all showed negative results. Blood culture and autoantibody profile were both negative. Anti-infective treatments with ceftizoxime, levofloxacin, ganciclovir, and oseltamivir were successively given. Oseltamivir was later changed to peramivir. Eight days later, the patient′s body temperature fluctuated between 38.4 ℃ and 38.6 ℃. Fibrinogen decreased to 1.49 g/L, serum ferritin increased to 1 218.91 μg/L, and soluble CD25 increased to 3 814 kU/L. Bone marrow smear showed hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis was diagnosed, which was considered to be caused by carbamazepine. Carbamazepine and the aforementioned anti-infective drugs were discontinued, and intravenous infusion of dexamethasone 15 mg once daily was administered. The patient′s body temperature decreased to 37.5 ℃. Six days later, intravenous infusion of etoposide 100 mg once was added. The next day, the patient no longer had fever, and laboratory indicators showed significant improvement. The patient′s laboratory indicators returned to normal in re-examination 3 months later.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

A 40-year-old male patient was treated orally with carbamazepine 0.1 g once daily for epilepsy. Twenty days later, the patient developed fever without obvious cause (highest body temperature 39.0 ℃), which showed no improvement after treatments with ribavirin and ibuprofen. Eleven days later, splenomegaly occurred, and serum ferritin was elevated (1 188.18 μg/L). Etiological testing showed positive influenza virus A/B antibody but negative nucleic acid; tests of Epstein-Barr virus, cytomegalovirus, novel coronavirus, respiratory syncytial virus, adenovirus, human rhinovirus, Mycoplasma pneumoniae, Mycobacterium tuberculosis, Leishmania donovani, Brucella, and Toxoplasma gondii all showed negative results. Blood culture and autoantibody profile were both negative. Anti-infective treatments with ceftizoxime, levofloxacin, ganciclovir, and oseltamivir were successively given. Oseltamivir was later changed to peramivir. Eight days later, the patient′s body temperature fluctuated between 38.4 ℃ and 38.6 ℃. Fibrinogen decreased to 1.49 g/L, serum ferritin increased to 1 218.91 μg/L, and soluble CD25 increased to 3 814 kU/L. Bone marrow smear showed hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis was diagnosed, which was considered to be caused by carbamazepine. Carbamazepine and the aforementioned anti-infective drugs were discontinued, and intravenous infusion of dexamethasone 15 mg once daily was administered. The patient′s body temperature decreased to 37.5 ℃. Six days later, intravenous infusion of etoposide 100 mg once was added. The next day, the patient no longer had fever, and laboratory indicators showed significant improvement. The patient′s laboratory indicators returned to normal in re-examination 3 months later.

Objective:The establish a standardized training assessment indicator system for young teachers in medical colleges and universities, and to improve the quality of training.Methods:A preliminary assessment indicator system was established through literature analysis and small-sample expert interviews, and then the Delphi method was used to conduct consultation with 40 experts familiar with the standardized training of young teachers in medical colleges and universities. The assessment indicator system was modified based on the opinions of the experts, and consultation was conducted again until basically consistent opinions were obtained from the experts. The analytic hierarchy process was used to assign weights to each indicator, and SPSS 17.0 was used for data analysis and processing.Results:After two rounds of expert consultation, 35 experts agreed with each indicator at a rate of more than 90%, and their opinions were basically consistent. The weight variation coefficient (W value) of each indicator ranged from 0.00 to 0.15, indicating a high degree of concentration. Finally, a standardized training assessment indicator system was established for young teachers, which consisted of 4 first-level indicators, 11 second-level indicators, and 35 third-level indicators.Conclusions:This assessment indicator system provides a basis for scientific evaluation of the quality of standardized training for young teachers in medical colleges and universities and improves the quality and efficiency of standardized training for young teachers by "promoting construction through evaluation and promoting supervision through evaluation".

Background and purpose:Currently,for patients with mid-to-low locally advanced rectal cancer and potentially resectable T4bM0 colon cancer,guidelines recommend neoadjuvant therapy strategies to enhance the response rate and increase the likelihood of conversion surgery.Among these patients,ypⅢ stage colorectal cancer(CRC)is assessed using the Union for International Cancer Control(UICC)/American Joint Committee on Cancer(AJCC)TNM staging system for postoperative pathological features.However,neoadjuvant therapy can lead to lymph node regression in the surgical area,resulting in an insufficient number of detected lymph nodes(less than 12),preventing classification according to conventional TNM staging.Thus,TNM staging often fails to predict the prognosis of ypⅢ patients who have undergone neoadjuvant therapy.This study aimed to evaluate the prognostic value of the positive lymph node ratio(LNR)in ypⅢ stage CRC patients treated with neoadjuvant therapy.Methods:Retrospective data was collected from ypⅢ stage CRC patients who received neoadjuvant therapy and underwent radical surgery at Fudan University Shanghai Cancer Center between 2008 and 2018.Collect clinical pathological characteristics such as age,gender,primary tumor location,tumor differentiation grade,pathological staging,and whether the patient has relapsed or died during follow-up at the time of surgery.Inclusion criteria:CRC patients who have received neoadjuvant therapy and surgery and have been confirmed to be stage Ⅲ by postoperative pathological examination.Exclusion criteria:① Preoperative imaging examination or intraoperative exploration reveals distant organ metastasis;② History of malignant tumors in the past;③ Multiple primary CRC.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:050432-4-2108*).The R software survminer package(surv_cutpoint algorithm)was used to calculate the optimal cutoff value for LNR relative to disease-free survival(DFS),and patients were divided into low and high LNR groups accordingly.Clinical pathological characteristics and DFS were compared between the two groups.COX proportional hazards regression models were employed to identify adverse pathological features,and survival plots along with prediction models for DFS were generated using the survival and rms packages.Results:A total of 489 patients were included,comprising 289 males and 200 females,with a median age of 56 years(23-80 years)and a median follow-up time of 1 062 d.During the follow-up period,164 patients(33.5%)died.In the entire cohort,204(41.7%)patients had fewer than 12 lymph nodes detected.The optimal cutoff value for LNR was 0.29,classifying 317 patients into the low LNR group(LNR≤0.29)and 172 patients into the high LNR group(LNR＞0.29).The high LNR group exhibited shorter DFS compared to the low LNR group[hazard ratio(HR)=2.103,95%CI:1.582-2.796,P＜0.000 1].Multivariate COX regression indicated that LNR was an independent prognostic factor for DFS(HR=1.825,95%CI:1.391-2.394,P＜0.001).The inclusion of LNR in a multicategory DFS nomogram prediction model effectively assessed DFS in stage Ⅲ CRC patients who had undergone neoadjuvant therapy.Conclusion:LNR is an independent prognostic factor for ypⅢ stage CRC patients,showing good predictive power for DFS when combined with other adverse pathological features.Therefore,incorporating LNR as a supplement to TNM staging can improve the accuracy of CRC prognosis assessment.

College students shoulder the heavy responsibility of the times and are the key to improving the quality of the peo-ple.The strategic goal of"Healthy China"has put forward higher requirements for general education courses in universities.Immunity and Health is a general education course offered by Shandong University for the entire school.While optimizing teaching content in the classroom to achieve knowledge goals,it guides students to think about the emotional value behind knowledge,improve immune intel-ligence,and thus achieve the mission of cultivating talents for the construction of a"Healthy China".This article explores the develop-ment process of the teaching mode of"Immunity and Health",which has important practical significance for enhancing general educa-tion in universities and promoting the purpose of"advocating a healthy and civilized lifestyle,shaping self-discipline and healthy behavior"in China.

Objective:To investigate the clinical efficacy of daratumumab-containing regimen in the treatment of multiple myeloma (MM) and the associated factors affecting patients' progression-free survival (PFS).Methods:A retrospective case series study was conducted. Clinical data of 21 MM patients who were treated with daratumumab-containing regimen in the Heping Hospital Affiliated to Changzhi Medical College from January 2021 to September 2023 were collected. The patients were treated with daratumumab (16 mg/kg intravenous drip) combined with other drugs for 28 d as 1 cycle until disease progression. Among the 21 cases, 6 cases were newly diagnosed multiple myeloma (NDMM), 7 cases were relapsed/refractory multiple myeloma (RRMM), and 8 cases were second-line treatment with daratumumab after the poor outcome of VRD (bortezomib + lenalidomide +dexamethasone) regimen at the time of initial treatment (daratumumab second-line treatment group). The efficacy of the patients after 2 cycles of daratumumab treatment was summarized; the PFS of the whole group and the NDMM and RRMM patients was analyzed by using Kaplan-Meier method, and log-rank test was used for comparison between the groups; the different status of disease, gender and age were included in the univariate and multivariate Cox proportional hazards models to screen the factors affecting the PFS of MM patients.Results:The median age [ M ( Q1, Q3)] of 21 patients was 62 years old (55 years old, 68 years old); 17 were male and 4 were female. After 2 cycles of daratumumab treatment, the overall remission rate (ORR) of the whole group was 85.7% (18/21), 2 cases (9.5%) achieved strict complete remission (sCR), 3 cases (14.3%) achieved complete remission (CR), 9 cases (42.9%) achieved very good partial remission (VGPR), 4 cases (19.0%) achieved partial remission (PR), 2 cases (9.5%) had stable disease and 1 case (4.8%) had disease progression. After 2 cycles of daratumumab treatment, all 6 NDMM patients were in remission, with 2 cases of sCR, 1 case of CR, and 3 cases of VGPR; 4 of 7 RRMM patients were in remission, with 1 case of CR and 3 cases of PR; 8 patients with daratumumab second-line treatment were in remission, with 1 case of CR, 6 cases of VGPR, and 1 case of PR; the difference in ORR among the 3 groups was statistically significant ( P = 0.010), the difference in ORR between patients with NDMM and daratumumab second-line treatment was not statistically significant ( P = 0.245), the ORR of NDMM patients was higher than that of RRMM patients, and the difference was statistically significant ( P = 0.029). The median follow-up time was 15.4 months (95% CI: 13.7-17.1 months). The median PFS time for the whole group was 10.6 months (95% CI: 7.3-15.5 months); the median PFS time was not reached in NDMM patients, the median PFS time was 14.6 months (95% CI: 2.1-27.2 months) in RRMM patients, the median PFS time was 9.6 months (95% CI: 9.5-9.7 months) in patients with daratumumab second-line treatment, and the difference in PFS among the 3 groups was not statistically significant ( P = 0.085). Multivariate Cox regression analysis showed that high age was an independent risk factor for PFS in MM patients ( HR = 1.12, 95% CI: 1.03-1.21, P = 0.009). Conclusions:Daratumumab has good results in treating MM and can be used as a first-line treatment option for NDMM patients, which may improve the remission rate of MM patients with previous ineffective treatment of VRD regimen, and may also improve the prognosis of RRMM patients. High age may be a risk factor for disease progression in MM patients treated with daratumumab.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.