Objective To investigate the best models of esophageal cancer surgical approaches,lymphadenectomy ranges and postoperative comprehensive treatment.Methods From January 1998 to December 2007 in 10 years,1 162 cases of different parts with esophageal cancer were analysized which were treated with surgically adopting sequential abdomen,chest,neck three-incision approaches.Taking three-step screening way of preoperative imaging,preoperative ultrasound localigation fineneedle aspiration biopsy cytology and intraoperative rapid fieezing pathological examination were applied to make the selectivity of the first-times cervico-thoraco-abdominal three-field lymph node dissection (3FLND),first-times standard thoracoabdominal two-field lymph node dissection (2FLND) and second-times third-field cervical lymphadenectomy.Meanwhile,we implemented actively postoperative comprehensive treatment and observed the overall clinical efficacy and long-term survival.Results In the group of 1 162 cases with esophageal cancer surgery.The operating resection rate was 100 ％,Radical resection of 97.6 ％ (1 134/1 162).Perioperative overall complication rate was 16.4 ％ (191/1 162).Anastigmatic fistula was 0.6 ％ (7/1 162).Five cases dead in 30 days after surgery.The whole group of lymph node metastasis rate was 52.6 ％ (611/1 162),lymph node metastasis degree in 12.1％ (3 092/25 564).Full group of the first-times 3FLND was 348 cases.The positive rate was 94.8 ％ (330/348),Implementing the first-times 2FLND was in 814 cases and the second-times thirdfield cervical lymph node dissection was performed in 89 cases.The postoperative complications of the 3FLND was significantly higher than that of 2FLND (23.6 ％ vs 13.4 ％).The difference was statistically significant (x2 =18.37,P ＜ 0.001).However,The difference was not statistically significant between 3FLND and 2FLND (P ＞ 0.05).There is no significant difference between the first-times 3FLND with the second-times 3FLND accumulating survival (P ＞ 0.05).But different degree of lymph node metastasis determined prognosis.The difference was significant (x2 =35.57,P ＜ 0.001).In our group the postoperative comprehensive treatment application rate was 87.2 ％.Surgery combined with comprehensive treatment overall 1,3,5 years survival rates were 92.1％,69.2 ％,49.6 ％ respectively.Conclusions The sequential three-incision approaches and selectivity of lymph node dissection have the radical nature thoroughly,fewer complications,high quality of life and the long-term survival advantages.It should be a widely used method in the clinical surgery of the esophageal cancer.Implementing the three-step screening way to selecting the first-times 3FLND,the firsttimes 2FLND and the second-times third-field cervical lymphadenectomy that have targeted strongly and high accuracy,a definite object in view and avoiding patient excessive trauma.Applying the comprehensive treatment after surgery and the re-treated of patients with recurrence that can further more improve the longterm survival of patients.The comprehensive treatment should be the target direction of the future development of esophageal cancer.

Objective To evaluate the value of magnetic resonance black-blood thrombus imaging (BTI) of the stage of disease in intracranial venous and sinus thrombosis(CVT).Methods From June 2015 to October 2016,37 patients with CVT diagnosed with routine imaging examinations in Beijing Xuanwu Hospital,Capital Medical University were enrolled prospectively,and they also underwent BTI examination.The patients were randomly divided into either a acute group (≤14 d,n=23) or a chronic group (>15 d,n=14) according to the time from the onset of symptoms to BTI.Signal to noise ratio(SNR) and contrast to noise ratio(CNR) difference between acute and chronic CVT groups were compared.The magnetic resonance venography (MRV) examination was used as a reference to calculate the accuracy of BTI on per-segment level.Results (1) The SNR and CNR of thrombosis in the acute group and chronic group were 206±97 and 94±41,201±96 and 86±40,respectively.There was significant difference between two groups (t=4.9 and 5.0 respectively;all P<0.01).(2) In 37 patients with CVT,the thrombi in 159 cerebral veins and venous sinus segments were detected with MRV.BTI identified the thrombi accurately in 152 vascular segments,and the thrombi in 352 vascular segments were eliminated.The diagnostic sensitivity and specificity were 95.6% (152/159) and 98.0% (352/359) respectively.Conclusion Achieving direct angiography of cerebral venous thrombosis,BTI technique can accurately differentiate acute or chronic thrombus.It has higher accuracy.

Objective To discuss the value of high-resolution magnetic resonance imaging (HR-MRI) in the etiological diagnosis of patients with head and neck artery occlusion.Methods From December 2015 to February 2017,25 consecutive patients with acute head and neck artery occlusion in Xuanwu Hospital,Capital Medical University were enrolled prospectively.The 32-channel head-neck combined coils were used to conduct head-neck integrated HR-MRI.The characteristics of proximal vascular wall of the occluded vascular segments and the signal features of thrombi in the middle and distal segments of occlusion were analyzed.The evaluation of the occlusive etiology was performed by two neurologists according to the clinical history,laboratory examinations,and imaging examinations of the patients,and the accuracy of conventional lumen imaging and conventional lumen imaging combined with HR-MRI in etiological classification were compared.Results Twenty-five patients with acute head and neck artery occlusion completed HR-MRI examinations.A total of 31 segments of the occluded vessels were diagnosed,and 21 of these were diagnosed with the conventional luminal imaging,30 were diagnosed with the conventional luminal imaging+HR-MRI,including 24 segments of atherosclerotic occlusion (n=19),4 segments of arterial dissecting occlusion (n=4),and 3 segments of arteritis occlusion (n=2).(2) In patients with atherosclerotic occlusion,the eccentric thickening was observed in the proximal wall of occlusive segment;the typical double-lumen or crescent-shaped hyperintense hematoma were observed in occlusive arterial dissection;long-segment annular thickening and enhancement were observed in the segment of arteritis occlusion.(3) The accuracy of the cause classification diagnosis of conventional luminal imaging and conventional luminal imaging+HR-MRI were 67.7% (21/31) and 96.8% (30/31) respectively (P<0.01).Conclusions Compared with the luminal imaging,the head and neck combined HR-MRI can reveal the arterial wall characteristics of the initial segment of occlusion.It has certain advantages in the interpretation of the causes,such as atherosclerosis,arterial dissection and arteritis.

OBJECTIVE: To observe the hepatic injury induced by combined exposure to diethylhexyl phthalate( DEHP) and bisphenol A( BPA) in rats and explore the mechanism of oxidative stress. METHODS: Thirty-two specific pathogen free healthy male SD rats were randomly divided into control group,DEHP(750 mg/kg body weight) group,BPA(100 mg/kg body weight) group and combined exposure group,with 8 rats in each group. The rats were gavaged once per day,7 days per week,for 6 weeks. The changes of liver organ coefficient and histopathology were observed. The activities of superoxide dismutase( SOD), glutathione peroxidase( GSH-Px) and the levels of hydrogen peroxide( H2 O2),malondialdehyde( MDA) were detected by spectrophotometry. The relative mRNA expression of antioxidant gene nuclear factor erythroid-2 related factor 2( Nrf2),heme oxygenase-1( HO-1),glutamate cysteine ligase catalytic subunit( Gclc),thioredoxin reductase( Txnrd),superoxide dismutase 3( Sod3) and glutathione peroxidase 1( Gpx1) in liver tissue were examined by real-time fluorescent quantitative polymerase chain reaction. RESULTS: The body weight of DEHP exposure group was lower than that of control group from the beginning of the 2 nd week( P < 0. 05),and the body weight of combined exposure group was lower than control group from the beginning of the 3 rd week( P < 0. 05). The liver mass and organ coefficients in DEHP group and combined exposure group were significantly higher than that of control group( P <0. 05). The results of pathology examination showed that there was necrosis of liver cells in DEHP group,vacuolar degeneration in cytoplasm of BPA group,and severe inflammatory cell infiltration in combined exposure group. The activity of SOD and GSH-Px of each exposure group was reduced( P < 0. 05),the H2 O2 level of each exposure group was increased(P < 0. 05),meanwhile the MDA level in the liver tissue of the BPA group and the combined exposure group increased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1 and Gpx1 in each exposure group were decreased( P < 0. 05),the relative mRNA expression of Gclc,Txnrd and Sod3 in DEHP group and mixed exposure group were decreased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1,Gclc,Txnrd and Sod3 in combined exposure group were decreased compared with the BPA group( P < 0. 05).CONCLUSION: Under the conditions of this study,DEHP and BPA alone or in combination could cause hepatic injury. The combined effect was greater than single effect. The effect of DEHP was greater than that of BPA. The liver injury induced by DEHP and BPA was related to Nrf2 signaling pathway.

OBJECTIVE: To investigate the mechanism of calcium ion(Ca~(2+))/calcineurin(CaN) signaling pathway in bisphenol A(BPA)-induced interleukin-6(IL-6) secretion in macrophages. METHODS: Raw 264.7 cells in logarithmic growth phase were divided into control group, activator group, BPA low-, medium-and high-dose groups and inhibitor group. The cells in control group were treated with 0.10% dimethyl sulfoxide. The activator group was treated with lipopolysaccharide at mass concentration of 2 mg/L. The 3 BPA groups were treated with BPA at final concentrations of 1, 10, or 100 μmol/L. Two sets of verapamil or tacrolimus(FK506) groups were given verapamil at the final concentration of 10 or 30 μmol/L; or final concentration of FK506 at 250 or 500 nmol/L. Then the cells were treated with final concentration of 100 μmol/L BPA. The cells were collected at 4, 12, and 24 hours. The mRNA expression of IL-6 and CaN at 4 and 12 hours were detected by real-time fluorescence quantitative polymerase chain reaction. The relative expression of IL-6 and CaN protein was detected at 24 hours by enzyme-linked immunosorbent assay, and the intracellular Ca~(2+) level was detected at 4 hours using a single-tube multi-function detector. RESULTS: At 12 hours, the mRNA expression of IL-6 in the 100 μmol/L BPA group was higher than that in control group, activator group and the 1 and 10 μmol/L BPA groups(P<0.05), and higher than that in the 10 and 30 μmol/L verapamil groups, and in the 250 and 500 nmol/L FK506 groups(P<0.05). The mRNA expression of CaN in the 100 μmol/L BPA group was higher than that in control group, activator group and 1 and 10 μmol/L BPA groups(P<0.05), and higher than in 10 and 30 μmol/L verapamil groups(P<0.05). The relative expression of IL-6 protein in the 100 μmol/L BPA group was higher than that in control group, activator group and 1 and 10 μmol/L BPA groups(P<0.05). The relative expression of CaN protein in 100 μmol/L BPA group and 10 and 30 μmol/L verapamil groups were higher than that in control group and activator group(P<0.05). The relative expression of CaN protein in the 10 and 30 μmol/L verapamil groups were lower than that in the 100 μmol/L BPA group(P<0.05). The intracellular Ca~(2+) level in the 100 μmol/L BPA group was higher than that in control group and activator group(P<0.05). The intracellular Ca~(2+) level in the 10 μmol/L verapamil group was lower than that in the 100 μmol/L BPA group(P<0.05). CONCLUSION: BPA might promote the secretion of IL-6 through Ca~(2+)/CaN signaling pathway in macrophages.

OBJECTIVE: To investigate the effects of combined exposure to di(2-ethylhexyl) phthalate(DEHP) and bisphenol A(BPA) on glucose metabolism in female rats during gestational and lactation periods, and its possible mechanism. METHODS: Twenty-four specific pathogen free pregnant SD rats were randomly divided into control group, DEHP group, BPA group, and combined exposure group, with 6 rats in each group. From the 5 th day of gestation to the 21 st day after birth of the offspring, the rats in the DEHP group were treated with DEHP 600 mg/kg body weight(bw); rats in BPA group were treated with 80 mg/kg bw BPA, and rats in combined exposure group were treated with 600 mg/kg bw DEHP and 80 mg/kg bw BPA by intragastric perfusion, while the rats in the control group were given the same amount of corn oil, once per day. After exposure, maternal rats were sacrificed immediately. The levels of glucose metabolism related indicators in liver tissues and serum were examined, and the mRNA and protein expression of phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(AKT) signaling pathway related factors in liver tissues were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot. RESULTS: Except for the activity of phosphoenolpyruvate carboxykinase(PEPCK) in BPA group, the levels of liver glycogen and serum high density lipoprotein cholesterol(HDL-C) in rats of the 3 exposure groups decreased(P<0.05), while the activity of serum PEPCK and the level of low density lipoprotein cholesterol(LDL-C) increased(P<0.05) compared with rats in the control group. The levels of liver glycogen and serum HDL-C in the combined exposure group were lower than that in the BPA group(P<0.05), while the level of serum LDL-C were lower than that in DEHP group and BPA group(P<0.05). The levels of serum glycosylated serum protein, total cholesterol and triglyceride in the 4 groups were not statistically different when compared with each other(P>0.05). Except for the PI3 K protein in DEHP group, the mRNA and protein expression of PI3 K, AKT, and glucose transporter 4 in liver tissues of rats in the 3 exposure groups decreased(P<0.05), and the mRNA expression of forkhead box protein 1(Foxo1) decreased(P<0.05), but the protein expression of FOXO1 increased(P<0.05) compared with the control group. CONCLUSION: Exposure to DEHP or BPA during pregnancy and lactation can cause glucose metabolism disorders in rats. The combined exposure of DEHP and BPA has certain synergistic effect. This process may be achieved through the PI3 K/AKT signaling pathway.

Currently， the ethical review model for organ donation and transplantation in domestic hospitals is generally characterized by suddenness， unpredictability， tight time， difficulty in convening meetings and training committee members， as well as generally low quality and efficiency of ethical review， which cannot meet clinical needs and cause the waste of some scarce resources. The team of the Clinical Application Center of Human Organ Transplantation and the Ethics Committee of the First People’s Hospital of Kunming combine more than 10 years of review practice experience， as well as continuously explore and optimize the ethical review process and operating procedures for organ donation and transplantation. The special application has been approved and jointly developed with Soochow University and the Medical Ethics Committee of Fujian Province to build a full-process information software system management platform for organ ethical review of donation and transplantation， giving the full play the advantages of the review information system in improving work efficiency and review quality， facilitating full-process information management， and conducting online training and learning for committee members， with a view to providing a specialized practical model for addressing the difficulties and challenges related to ethical review of human organ donation and transplantation.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2