[摘 要] 目的：观察白细胞介素-37（IL-37）在乳腺癌患者的表达变化对CD8+ T细胞活性的影响。方法：纳入2020年7月至2022年9月在新乡医学院第一附属医院就诊的46例乳腺癌患者、24例乳腺良性肿瘤患者、20例对照者。采集外周血，分离血浆和外周血单个核细胞（PBMC），收集接受手术治疗的乳腺癌患者肿瘤组织和癌旁组织，分离组织中肿瘤浸润淋巴细胞（TIL），纯化CD8+ T细胞。ELISA法检测IL-37、可溶型单免疫球蛋白IL-1受体相关蛋白（SIGIRR）表达，实时定量PCR法检测组织中IL-37 mRNA，流式细胞术检测CD8+ T细胞中IL-18受体α链（IL-18Rα）和SIGIRR表达。外源性IL-37刺激纯化的CD8+ T细胞，与乳腺癌细胞系MCF-7共培养，通过测定乳酸脱氢酶水平计算靶细胞死亡比例，ELISA法检测上清中穿孔素、颗粒酶B、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）水平。结果：乳腺癌患者血浆IL-37水平高于乳腺良性肿瘤患者[（554.17 ± 96.63）pg/mL vs （499.52 ± 78.66）pg/mL，P = 0.020]和对照者[（483.97 ± 47.23）pg/mL，P = 0.003]。乳腺癌患者肿瘤组织中IL-37 mRNA相对表达量高于癌旁组织[（1.88 ± 0.21） vs （1.00 ± 0.53）pg/mL，P < 0.001]。外周血IL-18Rα+ CD8+细胞比例、SIGIRR+ CD8+细胞比例、血浆可溶型SIGIRR水平在乳腺癌患者、乳腺良性肿瘤患者、对照者之间的差异无统计学意义（均P > 0.05）。CD8+ TIL表达IL-18Rα和SIGIRR的比例在肿瘤组织和癌旁组织之间的差异无统计学意义（P > 0.05）。重组人IL-37刺激后，CD8+ T细胞诱导靶细胞死亡比例、上清中IFN-γ和TNF-α水平在直接接触和间接接触共培养系统中均低于无刺激（均P < 0.05）。在直接接触共培养系统中，IL-37刺激后上清中穿孔素和颗粒酶B水平均低于无刺激（均P < 0.001），但在间接接触共培养系统中，上清中穿孔素和颗粒酶B水平在无刺激和IL-37刺激之间的差异无统计学意义（均P > 0.05）。结论：乳腺癌患者中IL-37水平升高可能参与诱导外周血和肿瘤微环境中CD8+ T细胞功能衰竭。

Objective To investigate the biomechanical characteristics of Salto Talaris tibial components with different heights at the bone-prosthesis interface during different gait support phases after total ankle replacement.Methods An ankle joint model was reconstructed using a weight-bearing CT from a 61-year-old female patient with ankle arthritis,and Salto Talaris tibial components with different heights(5,7,9,11 mm)were modelled to simulate the loading of the tibial-prosthesis during four gait support phases,and to analyse the micromotion and stresses at the bone-prosthesis interface.Results The 11 mm and 9 mm models had a poorer prosthesis stability,with the peak micromotion exceeding 50 μm and the peak internal tibial stresses of 30.75 MPa and 29.86 MPa,respectively,which exceeded the yield stress of the cancellous bone.The tibial stresses of the 7 mm and 5 mm models were within reasonable ranges and the average peak micromotions were only 42.66 μm and 40.32 μm.In contrast,the initial stability of the 5 mm model prosthesis was the best.Conclusions For total ankle replacement with Salto prosthesis,the height of the tibial component should be chosen appropriately,and the optimal height was about 5 mm.Excessive flexion and extension activities of the ankle joint should be avoided to maintain the stability of the prosthesis after surgery.This study provides a theoretical basis for the improvement of the structural parameters of the Salto prosthesis,which is valuable for the selection of clinical surgical prostheses and helps to improve the results of total ankle replacement.

Objective To investigate the biomechanical characteristics of Salto Talaris tibial components with different heights at the bone-prosthesis interface during different gait support phases after total ankle replacement.Methods An ankle joint model was reconstructed using a weight-bearing CT from a 61-year-old female patient with ankle arthritis,and Salto Talaris tibial components with different heights(5,7,9,11 mm)were modelled to simulate the loading of the tibial-prosthesis during four gait support phases,and to analyse the micromotion and stresses at the bone-prosthesis interface.Results The 11 mm and 9 mm models had a poorer prosthesis stability,with the peak micromotion exceeding 50 μm and the peak internal tibial stresses of 30.75 MPa and 29.86 MPa,respectively,which exceeded the yield stress of the cancellous bone.The tibial stresses of the 7 mm and 5 mm models were within reasonable ranges and the average peak micromotions were only 42.66 μm and 40.32 μm.In contrast,the initial stability of the 5 mm model prosthesis was the best.Conclusions For total ankle replacement with Salto prosthesis,the height of the tibial component should be chosen appropriately,and the optimal height was about 5 mm.Excessive flexion and extension activities of the ankle joint should be avoided to maintain the stability of the prosthesis after surgery.This study provides a theoretical basis for the improvement of the structural parameters of the Salto prosthesis,which is valuable for the selection of clinical surgical prostheses and helps to improve the results of total ankle replacement.

Objective:To analyze the clinical data of patients with end-stage ankle and hindfoot ar-thropathy who underwent tibiotalocalcaneal(TTC)arthrodesis by the same surgeon,explore the short-and mid-term clinical results,complications and functional improvement,and discuss the clinical progno-sis and precautions of TTC arthrodesis.Methods:Retrospective analysis was made on the clinical data of 40 patients who underwent TTC arthrodesis by the same surgeon from March 2011 to December 2020.In this study,23 males and 17 females were included,with an average age of(49.1±16.0)years.All the patients underwent unilateral surgery.The clinical characteristics,imaging manifestations,main diagno-sis and specific surgical techniques of the patients were recorded.The clinical outcomes were evaluated by comparison of the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot score and visual analogue scale(VAS)between pre-operation and at the last follow-up.The fusion healing time,symptom improvement(significant improvement,certain improvement,no improvement or deterioration)and postoperative complications were also recorded.Results:The median follow-up time was 38.0(26.3,58.8)months.The preoperative VAS score was 6.0(4.0,7.0),and the AOFAS score was 33.0(25.3,47.3).At the last follow-up,the median VAS score was 0(0,3.0),and the AOFAS score was 80.0(59.0,84.0).All the significantly improved compared with their preoperative corre-sponding values(P＜0.05).There was no wound necrosis or infection in the patients.One patient suf-fered from subtalar joint nonunion,which was syphilitic Charcot arthropathy.The median bony healing time of other patients was 15.0(12.0,20.0)weeks.Among the included patients,there were 25 cases with significant improvement in symptom compared with that preoperative,8 cases with certain improve-ment,4 cases with no improvement,and 3 cases with worse symptoms than that before operation.Con-clusion:TTC arthrodesis is a reliable method for the treatment of the end-stage ankle and hindfoot ar-thropathy.The function of most patients was improved postoperatively,with little impact on daily life.The causes of poor prognosis included toe stiffness,stress concentration in adjacent knee joints,nonunion and pain of unknown causes.

Objective The objective of this study was to investigate the expression of interleukin-38(IL-38)in patients with breast cancer and its regulatory function to CD8+T cell activity.Methods 44 patients with breast cancer,25 patients with benign breast tumor,and 20 controls,who were treated in the First Affiliated Hospital of Xinxiang Medical University from July 2020 and Sep-tember 2022.Mononuclear cells from plasma and peripheral blood of all subjects were isolated,tumor-infiltrating lymphocytes from tumor tissues of breast cancer patients were isolated,and CD8+T cells were purified.IL-38 protein level in the plasma was measured by enzyme-linked immunosorbent assay(ELISA).The relative level of IL-38 mRNA in the tissue was semi-quantified by real-time quantitative PCR.Recombinant human IL-38 was used to stimulate CD8+T cells from peripheral blood and tumor tissue from patients with breast cancer.A co-culture system was established between CD8+T cells and breast cancer MCF-7 cell line.The percentage of target cell death was calculated by measuring lactate dehydrogenase level in the supernatants.The levels of perforin,granzyme B,inter-feron-γ and tumor necrosis factor-α(TNF-α)in the supernatants were measured by ELISA.The immune checkpoint molecules ex-pression in CD8+T cells were detected by flow cytometry.Results The levels of plasma IL-38 were significantly higher in patients with breast cancer(74.23±19.88 pg/mL)compared with in patients with benign breast tumor(62.87±16.27 pg/mL,P=0.018)and controls(61.77±12.75 pg/mL,P=0.013).The relative expression of IL-38 mRNA in tumor tissues was significantly higher than in para-tumor tissues(1.57±0.22 vs.1.00±0.18,P<0.001).The proportion of target cell death induced by peripheral and tumor-in-filtrating CD8+T cells,and the levels of perforin and granzyme B secretion in direct contact co-culture group were higher than those in indirect contact co-culture group(P<0.05).There were no significant differences of either interferon-γ or TNF-α levels between di-rect contact and indirect contact co-culture group(P>0.05).In the direct contact co-culture group,the levels of target cell death pro-portion,perforin,granzyme B,interferon-γ and TNF-α l in the IL-38 stimulation group were lower than those in the non-stimulation group(P<0.05).In the indirect contact co-culture group,the target of cell death proportion,interferon-γ and TNF-α the IL-38 stimulation group were also lower than those in the non-stimulation group(P<0.05).However,there were no statistical differences of either perforin or granzyme B levels between the IL-38 stimulation group and non-stimulation group within the indirect contact co-culture group(P>0.05).There were also no differences in the levels of immune checkpoint molecules in CD8+T cells between the non-stimulation group and the IL-38 stimulation group(P>0.05).Conclusion Highly expressed IL-38 in patients with breast cancer may be involved in inducing CD8+T cell functional failure.

Objective:To observe the difference in the effect of simple titanium plate internal fixation and titanium plate internal fixation combined with titanium nail intermaxillary traction in the treatment of jaw fractures and their impact on the oral and maxillofacial function of patients.Methods:From August 2016 to May 2021, 94 patients with jaw fractures admitted to the Department of Stomatology, Linyi Central Hospital, Shandong (supplementing the gender, age range and average age of the patients), were divided into 47 cases in the control group, and the titanium plates were used alone, combined operation group 47 cases, titanium plate internal fixation combined with intermaxillary traction with titanium nails. The changes of oral and maxillofacial function and fracture healing were measured before operation and 3 months after operation, and the perioperative indicators and postoperative complications were recorded.Results:Three months after operation, the scores of maxillofacial function, mouth function and masticatory function in the combined operation group (0.52±0.09 points, 0.67±0.12 points, 0.58±0.08 points) were significantly lower than those in the control group (1.05±0.21 points, 1.14±0.22 points, 1.02±0.21 points) ( t=15.90, 12.86, 13.42, P<0.05). The effective rate of the combined operation group was 95.74% (45/47), which was significantly higher than that of the control group (80.85%, 38/47) (χ 2=5.05, P<0.05); there was no significant difference in operation time and hospitalization time between the groups ( P>0.05), the fracture healing time in the combined surgery group (65.02±7.06) d was significantly shorter than that in the control group (82.69±10.25) d ( t=9.73, P<0.05). The postoperative complication rate of combined treatment group was 6.38% (3/47), which was significantly lower than the control group 21.28% (10/47) (χ 2=4.37, P<0.05). Conclusions:In the treatment of jaw fractures, titanium plate internal fixation combined with titanium nail intermaxillary traction treatment can significantly improve the oral and maxillofacial function of patients, promote postoperative fracture healing, improve curative effect and reduce the incidence of complications compared with simple titanium plate internal fixation.

Objective     To investigate the clinical characteristics, risk factors and perioperative outcome of prolonged mechanical ventilation (PMV) in elderly patients undergoing coronary artery bypass grafting (CABG). Methods     The data of elderly patients receiving CABG in the Nanjing First Hospital from January 2013 to June 2019 were collected. All patients were divided into a control group and a PMV group according to whether ventilation time≥24 h. The clinical characteristics and risk factors of PMV were compared between the two groups. Variables were 1∶1 balanced through propensity score matching (PSM) and perioperative outcomes of two groups was analyzed. Results     Finally 956 patients were collected, including 187 in the PMV group and 769 in the control group. There were 586 males and 370 females aged 70-94 (74.3±3.5) years. Compared with the control group, the PMV group had higher rates of smoking,  preoperative renal impairment, intraoperative blood transfusion and intra-aortic balloon pump (IABP) implantation, worse cardiac function, lower glomerular filtration rate and ejection fraction, larger left atrial diameter, longer cardiopulmonary bypass time and aortic cross-clamping time (P<0.05). There was no statistical difference in other clinical data between the two groups (P>0.05). Binary multivariate logistic regression analysis showed that females, smoking, chronic obstructive pulmonary disease, left ventricular ejection fraction≤56.0%, cardiopulmonary bypass time>106.0 min, IABP implantation and intraoperative blood transfusion were independent risk factors for PMV in elderly patients. After PSM, there were 146 patients in the control group and the PMV group, respectively. The PMV group had longer ICU stay and length of hospital stay and more drainage volume compared with the control group (all P<0.05). There was no statistical difference in perioperative mortality or other complications between the two groups (all P>0.05). Conclusion    There are a lot of factors associated with PMV of the elderly patients undergoing on-pump CABG. In order to establish a complete and formal PMV prediction model, clinicians can make a further step of assessment according to perioperative elements, and improve the prognosis of such patients.

Objective:To evaluate the role of hippocampal hemeoxygenase-1 (HO-1) in electroacupuncture (EA)-induced reduction of lipopolysaccharide (LPS)-induced brain injury in mice.Methods:Twenty-four healthy adult C57BL/6J mice of both sexes, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), LPS-induced brain injury group (LPS group), LPS plus EA group, and LPS plus EA plus HO-1 inhibitor zinc protoporphyria (ZnPP) group (LPS+ EA+ ZnPP group). A virus carrying calcium ion fluorescent probes was injected into and an optical fiber was implanted into the hippocampal CA1 region to record changes in the calcium fluorescence signals.Three weeks later, Baihui, Quchi and Zusanli acupoints were stimulated with constant voltage (2/15 Hz) and disperse-dense waves for 30 min once a day for 5 consecutive days, and the stimulation intensity was defined as less than 1 mA causing slight muscle contraction.ZnPP 50 μmol/kg was intraperitoneally injected at 12 h before each stimulation in LPS+ EA+ ZnPP group, and the equal volume of normal saline was given instead in the other groups.After the end of EA stimulation on the last day, LPS 5 mg/kg was intraperitoneally injected to induce brain injury.Open field tests were performed at 1 day after LPS injection to record the number of rearing and amplitude of neuronal calcium signals during rearing.Novel object recognition tests were conducted at 3 days after LPS injection, and the exploration index and amplitude of neuronal calcium signals while exploring novel objects were recorded.The mice were sacrificed after the end of behavioral testing, and the brain tissues were obtained and stained by Nissl, and the neurons in the hippocampal CA1 region were counted. Results:Compared with group C, the number of rearing and amplitude of calcium signals in neurons in the hippocampal CA1 region during rearing were significantly decreased, the exploration index and amplitude of calcium signals in neurons in the hippocampal CA1 region while exploring novel objects were decreased, and the neuron counts were reduced in LPS, LPS+ EA and LPS+ EA+ ZnPP groups ( P<0.05 or 0.01). Compared with group LPS, the number of rearing and amplitude of calcium signals in neurons in the hippocampal CA1 region during rearing were significantly increased, and the exploration index and amplitude of calcium signals in neurons in the hippocampal CA1 region while exploring novel objects were increased in group LPS+ EA ( P<0.05), and no significant change was found in the parameters mentioned above in group LPS+ EA+ ZnPP ( P>0.05). Compared with group LPS+ EA, the number of rearing and amplitude of calcium signals in neurons in the hippocampal CA1 region during rearing were significantly decreased, and the exploration index and amplitude of calcium signals in neurons in the hippocampal CA1 region while exploring novel objects were decreased in group LPS+ EA+ ZnPP ( P<0.05). Conclusion:The mechanism by which EA reduces LPS-induced brain injury is related to the activation of the endogenous protective mechanism HO-1 in mice.

Objective: To summarize the experience of reoperations on patients who had late complications related to previous aortic surgery for Stanford type A dissection. Methods: From August 2008 to October 2016, 14 patients (10 male and 4 female patients) who underwent previous cardiac surgery for Stanford type A aortic dissection accepted reoperations on the late complications at Department of Thoracic and Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University. The range of age was from 41 to 76 years, the mean age was (57±12) years. In these patients, first time operations were ascending aorta replacement procedure in 3 patients, ascending aorta combined with partial aortic arch replacement in 4 patients, aortic root replacement (Bentall) associated with Marfan syndrome in 3 patients, aortic valve combined with ascending aorta replacement (Wheat) in 1 patient, ascending aorta combined with Sun′s procedure in 1 patient, Wheat combined with Sun′s procedure in 1 patient, Bentall combined with Sun′s procedure in 1 patient. The interval between two operations averaged 0.3 to 10.0 years with a mean of (4.8±3.1) years. The reasons for reoperations included part anastomotic split, aortic valve insufficiency, false aneurysm formation, enlargement of remant aortal and false cavity. The selection of reoperation included anastomotic repair, aortic valve replacement, total arch replacement and Sun′s procedure. Results: Of the 14 patients, the cardiopulmonary bypass times were 107 to 409 minutes with a mean of (204±51) minutes, cross clamp times were 60 to 212 minutes with a mean of (108±35) minutes, selective cerebral perfusion times were 16 to 38 minutes with a mean of (21±11) minutes. All patients survived from the operation, one patient died from severe pulmonary infection 50 days after operation. Three patients had postoperative complications, including acute renal failure of 2 patients and pulmonary infection of 1 patient, and these patients were recovered after treatment. Thirteen patients were finally recovered from hospital. The patients were followed up for 16 to 45 months, and no aortic rupture, paraplegia and death were observed in the follow-up. Conclusions Patients for residual aortic dissection after initial operations on Stanford type A aortic dissection should be attached great importance and always need emergency surgery, but the technique is demanding and risk is great for surgeons and patients, which need enough specification and accurate on aortic operation. More importantly, the Sun′s procedure also should be performed on the treatment of residual aortic dissection or distal arch expansion, and obtains the short- and long-term results in the future.

Objective To establish the background information of physiological parameters for germ?free ( GF ) Taihu piglets. Methods In this study we selected 25 days old GF Taihu piglets and 4 conventional ( CV) littermates, the male and female ratio was 1∶3, to measure the normal clinical values of hematology and serum biochemistry, immunoglobu?lin concentration and main organ coefficients. The analysis of relative growths of main organ weight to body weight was con?ducted in the Taihu GF and CV pigs by allometric scaling model. Results (1) Twelve hematological parameters and 8 blood biochemical parameters in the GF piglets were significantly lower than those in CV pigs (P<0?05). (2) The aver?age body weight, IgM concentration of GF pigs and CV pigs had significant difference ( P <0?05 ) , and no mesenteric lymph nodes were found in the GF pigs. (3) The gut weight had the largest allometric association with body weight in the GF pigs, while spleen weight has the largest allometric association with body weight in the CV pigs. Both the weight of heart and stomach in CV and GF pigs had a negative allometric association with body weight (allometric coefficient b<1), respectively. Conclusions Different microbe control grades affect the body weight, hematology and serum biochemistry, expression of immunoglobulin and development of main organs in laboratory pigs.