It is necessary to improve the stability of human serum albumin in response to the complex temperature, light and other conditions during the manufacture and storage. In this paper, the stabilization effect and simple stabilization mechanism of ligands on albumin were described from the perspective of ligand binding to albumin.Through review and comparison, it can be concluded that the common ligand sodium octanoate mainly plays a role in improving thermal stability, and the common ligand N-acetyl-L-tryptophan mainly plays a role in improving antioxidant activity, N-acetyl-L-methionine has better antioxidant and anti-photooxidation than N-acetyl-L-tryptophan.

Objective:Object To evaluate the therapeutic effectiveness of postoperative adjuvant mitotane therapy in the context of adrenocortical carcinoma (ACC) by using a meta-analysis methodology.Methods:A comprehensive literature review was conducted by systematically searching the PubMed, EMBASE, Web of Science, and Cochrane Library databases. The search spanned from the establishment of each database to October 2023. Search terms, "mitotane", "adrenocortical carcinoma" or synonyms. Inclusion criteria, Studies comparing outcomes (overall survival (OS) and/or recurrence-free survival (RFS)) in ACC patients with or without mitotane, reporting adjusted hazard ratios (HR) in multivariate Cox regression. Exclusion criteria, Patients with distant metastases, RI(Microscopic residual tumor) rection of ACC, or adjuvant chemotherapy. Data extracted on mitotane treatment concentration, duration, and tumor stage. A meta-analysis was conducted utilizing R4.2.2 software to assess the impact of ACC on OS or RFS through the calculation of HR and 95% confidence intervals (CI). Subgroup analysis of RFS was conducted based on the use of mitotane to reach effective levels or adequate duration, as well as tumor stage ≤T 3. Results:A meta-analysis was conducted, including a total of 15 studies and involving 2084 patients with ACC. Of these patients, 991 received post-surgical treatment with mitotane, while 753 had ACC classified as stages ≤T 3. The results showed that adjuvant mitotane therapy in the ACC group after surgery led to significantly improved OS ( HR=0.45, 95% CI 0.34-0.58, I2=0, P=0.79) and RFS ( HR=0.65, 95% CI 0.51-0.83, I2=76%, P<0.01) compared to non-adjuvant mitotane therapy. Subgroup analysis further revealed that patients with effective mitotane concentration or sufficient time after surgery[Subgroup a(Median follow-up duration < 45 months): HR=0.59, 95% CI 0.44-0.79, I2=0, P=0.38; Subgroup b(Median follow-up duration ≥ 45 months): HR=0.93, 95% CI 0.90-0.96, I2=0, P=1.00 ]and with ≤T 3 stage ACC ( HR=0.61, 95% CI 0.47-0.79, I2=0, P=0.62)had better RFS compared to those who did not achieve the requisite mitotane concentration or postoperative interval, as well as patients with stage T 4 ACC. Conclusions:The administration of adjuvant mitotane therapy following ACC resection has been shown to significantly extend patients' OS and RFS, particularly when the therapy achieves optimal concentration or is administered for an adequate duration. Furthermore, in patients with ACC classified as stage ≤T 3, the effect of adjuvant mitotane therapy on prolonging RFS appears to be more consistent and reliable.

Objective To explore the effect of low molecular weight heparin calcium on coagulation function and platelet(PLT)in patients before and after anterolateral thigh flap transplantation.Methods Fifty patients with skin and soft tissue defects of hands and feet treated in Wuxi Ninth Hospital and Jiujiang No.1 People's Hospital from January to December 2022 were selected as the study objects.They were divided into observation group(26 cases)and control group(24 cases)according to random number table method.Patients in observation group received low molecular weight heparin calcium 12h before surgery,and continued to receive routine treatment once a day after surgery.Patients in control group began to use low molecular weight heparin calcium routinely 4h after surgery,once a day.The coagulation function and PLT before and after surgery were compared between two groups.Results There were no significant differences in incidences of vascular crisis and skin flap necrosis between two groups(P>0.05).Five patients in observation group received intraoperative or postoperative blood transfusion,which was excluded in further analysis.On first day and third day after surgery,fibrinogen(FIB)and PLT in two groups were significantly higher than those before surgery,and thrombin time(TT)was significantly shorter than that before surgery(P<0.05).On third day after surgery,activated partial thromboplastin time(APTT)and prothrombin time(PT)in observation group were significantly longer than those before surgery(P<0.05).Before surgery,first day and third day after surgery,there were no significant differences in FIB,APTT,PT and TT between two groups(P>0.05).On third day after surgery,PLT of observation group was significantly higher than that of control group(P<0.05).Conclusion Both FIB and PLT were higher after surgery regardless of the use of low molecular weight heparin calcium before and after surgery,and FIB and PLT were more significantly higher in patients treated 12h before surgery.

Objective:To investigate the effects of preoperative mammalian target of rapamycin(mTOR )inhibitor on partial nephrectomy for renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML).Methods:A retrospective analysis was conducted on clinical data from 13 patients who were diagnosed with TSC-RAML and treated at Peking Union Medical College Hospital between August 2019 and July 2022. This cohort included 4 males and 9 females, with ages ranging from 22 to 66 years. All patients underwent partial nephrectomy, with 2 patients requiring two-stage surgeries due to bilateral RAMLs, resulting in a total of 15 surgeries being performed. Preoperative mTOR inhibitors, specifically everolimus (10 mg/d) or sirolimus (2 mg/d), were administered orally for at least 3 months prior to 7 of the surgeries. The effects of mTOR inhibitors on tumor size, tumor computed tomography attenuation value (CT value), and tumor CT enhancement were evaluated. The comparison of surgery-related clinical parameters was conducted between patients who received preoperative mTOR inhibitors and those who did not to assess the influences of mTOR inhibitors on surgery.Results:Compared to the baseline tumor, there was a significant reduction in tumor diameter after mTOR treatment [(6.4±3.1) cm vs. (8.7±3.9)cm], as well as in the CT value in both the unenhanced phase[(-18.63±48.73)HU vs. (-2.13±51.58)HU] and corticomedullary phase[(13.25±64.01)HU vs. (47.25±66.99)HU]. Additionally, tumor CT enhancement also decreased as compared with that before treatment [(31.88±18.20)HU vs. (49.38±20.63)HU]. Patients who received preoperative mTOR inhibitor showed a trend towards shorter operative time for removing per milliliter of tumor compared to those without preoperative mTOR inhibitor [1.06(0.18, 2.40) min/ml vs. 1.98(0.39, 5.03) min/ml] and so was the renal artery clamping time [0.17(0.03, 0.79) min/ml vs. 0.34(0.10, 1.71) min/ml]. Additionally, the amount of intraoperative bleeding for removing per milliliter of tumor was lower in patients with preoperative mTOR inhibitors compared to those without [0.72(0.19, 0.88) ml/ml vs. 1.69(0.59, 4.54) ml/ml].Conclusions:The administration of mTOR inhibitors before partial nephrectomy in patients with TSC-RAM have the potential to reduce tumor size and blood supply, as well as operative time, renal artery clamping time and intraoperative bleeding, which might contribute to surgery safety and preservation of renal function.

Objective:To analyze the clinical efficacy and safety of endoluminal treatment of complex renal artery aneurysm (RAA).Methods:The clinical data and follow-up results of 19 patients with complex RAA admitted to Renji Hospital, Shanghai Jiaotong University School of Medicine from November 2014 to September 2021 were retrospectively analyzed. Two patients were treated with simple spring coil embolization into the aneurysmal artery, 14 patients were treated with simple spring coil embolization of the aneurysmal cavity, and 3 patients were treated with stent-assisted + spring coil embolization technique. Based on the location of the aneurysm, RAA were classified into type Ⅰ, Ⅱ, and Ⅲ. 7 patients with type Ⅰ, 10 patients with type Ⅱ, and 2 patients with type Ⅲ were studied. Variance analysis was used to compare the differences in glomerular filtration rate(GFR) of the affected side when the tumor was located at different locations, and Pearson was used to analyze the correlation between the number of coils implanted and the size of the tumor and GFR.Results:Ten of the 19 patients who were underwent successful endoluminal intervention. The average size of the patients′ aneurysms was (20.89±6.65) mm, and the average number of spring coils implanted was 8.22±3.08. The preoperative and postoperative serum creatinine were in the normal range, and no RAA tumor enlargement or recurrence was found during the follow-up period. The postoperative GFR was abnormal in patients with type Ⅰ, type Ⅱ, and type Ⅲ renal aneurysms, and the mean GFR value differed among the three types of patients( P=0.003). There was a negative correlation between the postoperative GFR values of the affected kidney and the number of spring coils implanted ( P=0.047), and no significant relationship between GFR and aneurysm size. Conclusion:The endovascular technique is an effective and safe means of treating complex RAA.

Objective    To investigate the results of emergent aortic arch replacement using moderate hypothermic circulatory arrest and unilateral antegrade cerebral perfusion (MHCA+UACP). Methods    We retrospectively analyzed the clinical data of 146 patients who underwent emergent aortic arch replacement using MHCA+UACP in our institution from January 2008 to June 2018. There were 111 males and 35 females aged 60.3±7.2 years. According to different surgical approaches, patients were divided into two groups: a total arch replacement (TAR) group (n=104) and a semi arch replacement (SAR) group (n=42). Right axillary artery was cannulated for cardiopulmonary bypass (CPB) and cerebral perfusion. Core temperature at the onset of MHCA was 23.4±1.4 ℃. UACP was initiated at 18-22 ℃ with the flow of 5-10 ml/(kg·min). Flow was adjusted to maintain cerebral perfusion pressure of 50–60 mm Hg. Results    CPB time was 235.0±42.0 min. Aortic clamp time was 154.0±29.0 min. Circulatory arrest (CA) time was 48.1±13.0 min. The CPB time and CA time of the TAR group were longer than those of SAR group. Overall mortality rate was 9.6%. Complications included permanent neurological dysfunction (PND), temporary neurological dysfunction (TND), acute kidney injury (AKI) requiring dialysis and delayed extubation (mechanical ventilation time > 72 hours). Overall incidence of PND and TND was 2.7% and 6.8%, respectively. The incidence of AKI requiring dialysis was 4.1%. The incidence of delayed extubation was 21.9%. No difference of mortality rate or incidence of complications was found between the two groups. The average follow-up was 63.0±33.1 months. The 5-year survival rate was 72.6% in the TAR group and 85.5% in the SAR group. Conclusion    Emergent aortic arch replacement using MHCA+UACP can be accomplished with excellent results.

Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P＜0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P ＜ 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .

Objective To explore the inflammatory effect of exosomes derived from alveolar epithelial cells stimulated by lipopolysaccharide (LPS) on the alveolar macrophages (NR8383). Methods The alveolar epithelial cells disposed with different treatments were co-cultured with alveolar macrophages by using a Transwell system separately. Alveolar epithelial cells (RLE-6TN) were randomly divided into 4 groups: normal group, LPS-stimulated group, exosome inhibitor group, and exosome inhibitor pretreatment + LPS stimulation group. NR8383 cultured alone was considered as a blank control. After the 12-h co-culture, the real-time PCR (qPCR) was performed to examine the mRNA relative expression of IL-6, TNF-α, and IL-1β in NR8383 cells. To further explore the role of exosomes derived from RLE-6TN on alveolar macrophages mediated inflammationary response, the experimental exosomes (exosomes derived from LPS-induced RLE-6TN) and control exosomes exosomes derived from normal RLE-6TN were extracted by gradient ultracentrifugation. Transmission electron microscopy and Western blotting analyses was performed to identify the exosomes, and qNano particle diameter analyzer was conducted to measure the particle diameter of exosomes. In vitro, NR8383 cells were divided into 3 groups which were cultured with exosomes derived from LPS-stimulated RLE-6TN at a concentration of 10 μg/mL (experimental group), exosomes derived from untreated RLE-6TN at the same concentration of 10 μg/mL (control group), and the PBS at the same volume with experimental group (PBS group), respectively for 12 h. After the treatment, the phagocytosis of NR8383 cells was observed by laser confocal microscope and the release of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in supernatants of NR8383 was detected by enzyme-linked immunosorbent assay ELISA Results (1)In the co-culture experiment, the mRNA relative expression of pro-inflammatory cytokine in the LPS group was significantly increased compared with the blank control group (P<0.01), however comparing the exosome inhibitor pretreatment+LPS group with the LPS group, the expression of pro-inflammatory cytokine was decreased (P<0.01). (2) The extracted exosomes were observed as circular or elliptical vesicles with a diameter of 40-100 nm under the transmission electron microscopy. Western blotting analyses showed that the extracted exosomes express the protein marker, such as CD63 and CD9; After incubation with NR8383 cells for 5 h, laser scanning confocal microscope showed that the exosomes labeled with red fluorescent were uptaken by NR8383 cells. (3)After the exosomes derived from the LPS-disposed RLE-6TN and the normal RLE-6TN cells were incubated with NR8383 cells respectively. The ELISA test showed that treated the alveolar macrophages with LPS induced alveolar epithelial secreted exosomes led to a robustly increased release of pro-inflammatory cytokine (P<0.01), but there was no significant difference between the control group and PBS group (P>0.05). Conclusions Exosomes derived from LPS-disposed alveolar epithelial cells activate the alveolar macrophage-mediated inflammatory response.

Objective To investigate the protective effect of sulodexide (SDX) on oxidized low density lipoprotein (ox-LDL) induced damage to human umbilical vein endothelial cell (HUVEC),and to discuss its mechanism.Methods By using CCK-8 method,the ox-LDL intervention HUVEC dose and the concentration of SDX were determined.The reactive oxygen species (ROS) assay kit was used to verify the protective effect of SDX on HUVEC.Real time fluorescent quantitation-polymerase chain reaction (RT-PCR) was employed to test the endothelial nitric oxide synthase (eNOS) and caveolin-1 mRNA expression;immunoblot assay was adopted to check the protein expression of phosphorylated eNOS (p-eNOS) and caveolin-1.The ability of cell migration was assessed by Transwell assay.Results Stimulated by 100 μg/ml concentration of ox-LDL,the cell viability of HUVEC decreased significantly (P＜0.01).After adding 125 LRU/ml concentration of LDX,the cell viability of HUVEC was remarkably improved (P＜0.01) and the production of ROS was strikingly decreased (P＜0.01).SDX could down-regulate the expression of caveolin-1 (P＜0.05) and up-regulate the expression of eNOS mRNA and p-eNOS (P＜0.05) for ox-LDL-damaged HUVEC,and markedly improve the migration ability of damaged HUVEC (P＜0.01).Conclusion By regulating the caveolin-1/eNOS signal route,SDX can improve impaired HUVEC cell migration ability,thus,to protect endothelial cells.

Background Retinal ischemia reperfusion injury (RIRI) is a common pathological process of many retinal vascular diseases with comprehensive pathogenesis mechanism.Researches showed that apoptosis of retinal cells and nerve fiber loss is the finally common pathway of RIRI,and Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway is a newly discovered signal transcript channel in recent years,which is involved in varieties of pathological processes.However,whether JAK-STAT pathway is associated with RIRI is still unelucidated.Objective This study was to investigate the time course of activation of JAK-STAT signal pathway and its significance during RIRI.Methods Forty clear adult male Sprague-Dawley rats were randomized into RIRI 6-hour,12-hour,24-hour and 48-hour groups.RIRI models were induced in lateral eyes of the rats by perfusing normal saline solution into the anterior chamber to elevate intraocular pressure (IOP) to 110 mmHg for 60 minutes and then allowing reperfusion,and the fellow eyes of the rats served as normal control group.The rats were sacrificed and the eyeballs were enucleated at 6,12,24 and 48 hours after reperfusion.The expressions of JAK2 and STAT3 protein (absorbance) in the retinas were located and detected by immunohistochemistry,and the relative expression levels of JAK2 and STAT3 mRNA in the retinas were detected by real-time fluorescence quantitative PCR.The use and care of the rats followed the ARVO Statement.Results Immunohistochemistry showed that JAK2 and STAT3 were faintly expressed in inner nuclear layer and retinal ganglion cells (RGCs) in the normal control group and strongly expressed in various RIRI groups.Significant differences were found in the expression intensities of JAK2 and STAT3 protein among the five groups (F =88.735,96.625,both at P ＜ 0.01).Compared with the normal control group,the expression intensities of JAK2 and STAT3 were enhanced in RIRI groups,with the peak values in RIRI 12-hour group (JAK2:t=4.308,5.559,5.315,4.726;all at P＜0.01.STAT3:t=5.047,7.843,6.281,4.887;all at P＜0.01).The thickening of inner retinal layer,loosening of retinal tissue,vacuolus degeneration of cells and decrease of RGCs were seen in the RIRI eyes.The relative expressing levels of the JAK2 mRNA and STAT3 mRNA in the retinas were significantly different among the groups (F =111.239,129.539;both at P＜0.01),and the relative expressing levels of JAK2 mRNA and STAT3 mRNA in the retinas were significantly increased in RIRI 6-hour,12-hour,24-hour and 48-hour groups in comparison with the normal control group (JAK2 mRNA:t=3.504,5.102,4.679,4.213;all at P＜0.01.STAT3 mRNA:t =6.541,8.787,5.693,5.898;all at P＜0.01).Conclusions The retinal morphology appears to be abnormal and RGCs are evidently decreased in rat eyes with RIRI,and the expressions of JAK2 and STAT3 in the retinas are simultaneously up-regulated,indicating that JAK-STAT signal pathway is involved during the RIRI process.