Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8⁺ T cell infiltration. The proportion of CD8⁺ T cells in the spleen continued to rise post-operation, while the proportion of CD4⁺ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.

Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

BACKGROUND:Current studies have confirmed that Ganoderma lucidum polysaccharides can promote nerve regeneration in neurodegeneration-related diseases.The occurrence of neurodegenerative diseases is closely related to mitochondrial dysfunction,but the role of Ganoderma lucidum polysaccharides on the regulation of apoptosis and mitochondrial function in neurodegenerative diseases is not yet clarified. OBJECTIVE:To explore the regulatory effects and mechanisms of Ganoderma lucidum polysaccharides on apoptosis and mitochondrial dysfunction in H2O2-induced SH-SY5Y cells. METHODS:SH-SY5Y cells were divided into three groups:control group,H2O2 group,and Ganoderma lucidum polysaccharides group.Cells in the control group were normally cultured.Cells in the H2O2 group were treated with 300 μmol/L H2O2 for 24 hours.In the Ganoderma lucidum polysaccharides group,the intervention with 300 μg/L Ganoderma lucidum polysaccharides was conducted first for 1-2 hours,followed by the addition of 300 μmol/L H2O2 for 24 hours.The mitochondrial membrane potential was detected by JC-1 kit.Apoptosis was detected by TUNEL staining kit.The activities of malondialdehyde and superoxide dismutase were detected by malondialdehyde test kit and superoxide dismutase test kit,respectively.The apoptosis and expression of mitochondrial dynamics-related proteins were detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the mitochondrial membrane potential and superoxide dismutase activity were significantly reduced,as well as apoptotic rate and malondialdehyde levels were significantly increased in the H2O2 group(P<0.05).After treatment with Ganoderma lucidum polysaccharides,the membrane potential and superoxide dismutase activities were significantly increased,and apoptotic rate and malondialdehyde levels were significantly reduced compared with the H2O2 group(P<0.05).(2)The expression levels of pro-apoptotic proteins Bax and Caspase-3 were significantly increased,but the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the H2O2 group compared with the control group(P<0.05).Compared with the H2O2 group,the levels of Bax and Caspase-3 were significantly decreased,but the expression of anti-apoptotic protein Bcl-2 was significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(3)Compared with the control group,the expression of mitochondrial splitting proteins Fis1 and p-Drp1 was significantly increased,but the expression of mitochondrial fusion proteins OPA1,Mfn1,and Mfn2 was decreased in the H2O2 group(P<0.05).Compared with the H2O2 group,Fis1 and p-Drp1 expression was significantly reduced,but the expression levels of OPA1,Mfn1,and Mfn2 were significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(4)The above results confirm that Ganoderma lucidum polysaccharides can attenuate H2O2-induced oxidative stress damage and apoptosis in SH-SY5Y cells by ameliorating mitochondrial dysfunction.

Objective To observe value of thin slice CT multiple signs combined with multiplanar reformation(MPR)for diagnosing tracheobronchial tuberculosis(TBTB).Methods Data of 234 TBTB patients who underwent chest thin slice CT scanning were retrospectively analyzed.MPR was performed,the direct signs and indirect signs of TBTB were observed.The diagnostic efficacy of axial plain CT images(direct observation)and of MPR combined with the former(combined observation)were compared.Results The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of direct observation was 38.88％(201/517),98.13％(1 789/1 823),85.53％(201/235),84.99％(1 789/2 105)and 85.04％(1 990/2 340),respectively,of combined observation was 91.10％(471/517),98.85％(1 802/1 823),95.54％(471/493),97.51％(1 802/1 848)and 97.14％(2 273/2 340),respectively.Significant differences of sensitivity,positive predictive value,negative predictive value and accuracy were found(all P＜0.001),whereas no significant difference of specificity was found between 2 methods(P＞0.05).Conclusion Thin slice CT multiple signs combined with MPR could be used to effectively diagnose TBTB.

Purpose To investigate the clinical pathologic features of five SMARCA4-deficient non-small lung cancers(SMARCA4-dNSCLCs).Methods Five cases of SMARCA4-dNSCLC was underwent by HE,immunohistochemical staining,and molecular detection,analyzed their clinicopathological char-acteristics and reviewed relevant literatures.Results All 5 ca-ses were male,and mean age was 66 years.Five patients had a history of smoking,three patients were treated with cough and blood in sputum as the first symptom,one was treated with a history of pulmonary tuberculosis combined with limb mobility disorder,and one was diagnosed with pulmonary nodules by physical examination.Under microscopic observation,tumor cells were poorly differentiated,with solid nest sheet distribu-tion,some with glandular structure,tumor cells had abundant e-osinophilic or transparent cytoplasm,vacuolar nuclear chroma-tin,nucleoli was visible,and nuclear mitosis was common.In-flammatory cell infiltration and sheet of necrosis were seen in the stroma.Immunohistochemical staining showed 5/5 diffuse ex-pression of CK(AE1/AE3)and CK7,5/5 loss expression of BRG1,1/5 diffuse expression of p40 and CK5/6,and Ki67 proliferating index ranged from 20％to 90％.FISH tests showed that 4/4 SMARCA4 genes missed.Five patients were followed up for 2-15 months,3 patients died and 2 patients survived.Conclusions SMARCA4-dNSCLC can have extensive morphologi-cal features,high degree of malignancy,and complicated treat-ment.BRG1 deficiency is helpful for diagnosis.Deepening the understanding of SMARCA4-dNSCLC can help the clinical cor-rect choice of treatment strategies and accurately evaluate patient prognosis.

Objective To investigate changes of laboratory indicators and pathological features of Henoch-Schonlein purpura nephritis(HSPN)children after crescent formation,and to explore non-invasive biomarkers for predicting crescent formation.Methods A total of 278 children with HSPN who were hospitalized from January 2018 to July 2023 were selected and divided into the crescent formation group(196 cases)and the non crescent formation group(82 cases)based on their crescent formation status.Patients in the crescent formation group were sub-divided into the cellular crescent formation group(52 cases)and the cellular fibrous crescent formation group(144 cases)based on the type of crescent formation.Laboratory indicators and pathological characteristics were compared between different groups.The correlation between each indicator and the proportion of crescent formation was analyzed.The influencing factors of crescent formation were analyzed by Logistic regression.Receiver operating characteristic(ROC)curves were plotted,and the effectiveness of laboratory indicators in predicting crescent formation was evaluated.Results Compared with the non crescent formation group,24-hour urine protein quantification(24 hUP),urine immunoglobulin G/creatinine(UGCR),urine red blood cell count(URBC),neutrophil/lymphocyte ratio(NLR),blood urea nitrogen(BUN)and triglycerides(TG)were significantly increased in the crescent formation group.There were increased proportion of diffuse mesangial hyperplasia(Mb),renal tubular atrophy or interstitial fibrosis(T1)(P＜0.05).Compared with the cellular crescent group,the proportion of glomerular segmental sclerosis or adhesion(S1)and T1 were increased,and the proportion of crescent formation was higher in the cellular fibrous crescent group.The proportion of capillary endothelial cell proliferation(E1)was decreased in the cellular crescent group(P<0.05).Spearman correlation analysis showed that 24 hUP,UGCR,URBC,NLR,BUN,TG,Mb and T1 were positively correlated with the proportion of crescent formation(all P＜0.05).The results of multivariate Logistic regression analysis showed that elevated UGCR and T1 were risk factors for crescent formation.The area under the curve(AUC)predicted by UGCR for crescent formation was 0.731(95%CI:0.667-0.795,P＜0.05),with an optimal cutoff value of 5.00 mg/mmol,sensitivity of 0.744 and specificity of 0.610.Conclusion UGCR can be used as a non-invasive biomarker to assist in evaluating crescent formation in children with HSPN.

ObjectiveTo evaluate the proficiency and consistency of domestic and foreign testing institutions in the field of veterinary drug residue detection in food， and to promote international cooperation and mutual recognition of testing results among these institutions. MethodsA robust statistical analysis was conducted on the testing results of 20 laboratories in eight countries and regions across North America， Europe， and Asia. The laboratories’ testing capabilities were evaluated using Z-score comparison. ResultsAmong the 20 participating laboratories， 18 achieved satisfactory results， resulting in a satisfaction rate of 90%， while 2 laboratories （10%） failed to meet the requirements. The satisfaction rate of domestic laboratories （100%） was higher than that of foreign laboratories （81.8%）. ConclusionDomestic laboratories perform better than overseas laboratories in determining veterinary drug residues in food. To enhance testing capabilities， these overseas laboratories with unsatisfactory evaluation results should strengthen their daily quality control and ensure traceability of original records.

The incidence of gastrointestinal malignancies is high in the population, and 40%?80% of gastrointestinal tumor patients suffer from malnutrition. The metabolic mechanism of tumor disease itself, and the perioperative stress reaction caused by surgical treatment can further aggravate malnutrition. Therefore, nutritional support should be routinely provided during the perioperative period in tumor patients with nutritional risk or malnutrition. For a long time, immunonutrients such as glutamine, ω-3 fatty acids, arginine and nucleotides have attracted much attention in the treatment of perioperative tumor patients. Most studies have shown that perioperative immunonutrition therapy not only improve nutritional deficiency and correct malnutrition, but also maintain immune function, reduce inflammation and maintain intestinal barrier integrity, to reduce postopera-tive complications and short postoperative duration of hospital stay. However, with the extensive clinical application and in-depth study of immunonutrition in recent years, there are still many doubts and controversies about its application in the perioperative gastrointestinal malignancies. The authors review the pharmacological mechanism and clinical application of perioperative immunonutrients, perioperative combined application of immunonutrients, and application timing and approach of immunonutrition in patients with gastrointestinal malignancies, so as to provide some clues for its subsequent clinical application.

Objective:To investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

Objectives:To analyze the potential biomarkers of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD) continuum.Methods:A prospective cohort study was consecutively conducted on 179 patients with AD continuum (135 presented with BPSD, 44 patients without BPSD as control) from Capital Medical University, Beijing Tiantan Hospital, the Chinese imaging biomarkers and lifestyle cohort between January 1, 2021 and December 31, 2022. Gender, age, body max index, education level, diagnosis, the apolipoprotein E epsilon4 allele (APOE ε4) carrier status, the scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), cerebrospinal fluid (CSF) AD-related pathological biomarkers (Aβ 42, Aβ 40, Aβ 42/40, tTau, pTau181), and blood biomarkers (white blood cell count, red blood cell count, hemoglobin, platelet, total bilirubin, albumin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose, erythrocyte sedimentation rate, homocysteine, vitamin B 12, folate) were compared between the two groups by using hypothesis testing and univariate logistic regression analysis. Multivariate logistic regression analysis was used to analyze the potential biomarkers associated with BPSD in patients with AD. Results:Among the 179 patients with AD continuum in the final analysis, 77 patients were men, 102 cases were women; 35 patients were identified with mild cognitive impairment (MCI) due to AD and 144 patients with AD dementia stage, the mean age was (66.54±9.75) years. Compared with those in control group, patients with BPSD had lower cerebrospinal fluid (CSF) Aβ 40 and blood hemoglobin levels [7.08 (4.42, 15.42) vs 9.62 (6.45, 12.12) pg/L, (132.70±13.37) vs (138.80±14.38) g/L] ( U=-1.856, t=2.579, P<0.05). The levels of CSF Aβ 40 ( OR=0.030, 95% CI: 0.001-0.760) and blood hemoglobin ( OR=0.051, 95% CI: 0.004-0.670) were independently negatively associated with BPSD in patients with AD continuum (both P<0.05). Conclusion:The decreased levels of CSF Aβ 40 and blood hemoglobin could be considered as potential biomarkers in detecting BPSD in patients with AD continuum.