Objective To investigate the protective effects and mechanisms of sulodexide on renal fibrosis induced by prolonged warm ischemia. Methods An in vivo ischemia-reperfusion injury (IRI) model was established in rats, which were randomly divided into Sham group, IRI 60 min group (IRI group), and IRI 60 min + sulodexide group (IRI+SDX group), with 20 rats in each group. Pathological examination was used to evaluate renal tissue injury and fibrosis levels in each group. Immunohistochemistry was performed to detect the expression levels of kidney injury molecule (KIM)-1, intercellular adhesion molecule (ICAM)-1, von Willebrand factor (vWF), transforming growth factor (TGF)-β, α-smooth muscle actin (SMA), and type I collagen (COL-1). Immunofluorescence staining was used to detect CD31 expression. Real-time quantitative polymerase chain reaction was employed to measure the expression of KIM-1, ICAM-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in renal tissues. Transmission electron microscopy was used to observe the structure of the renal glycocalyx. Evans blue dye was injected to assess renal vascular permeability. Rat survival was recorded, and serum levels of syndecan (SDC)-1, heparan sulfate (HS) and serum creatinine were measured. An ex vivo perfusion model was also established, with rats randomly assigned to either the hypothermic oxygenated machine perfusion (HOPE) group or the HOPE+SDX group (five rats per group). Perfusion parameters were recorded after 2 hours of ex vivo perfusion. Results One day after reperfusion, compared with the Sham group, the IRI group exhibited more severe renal tissue injury, higher tubular injury scores, increased expression of KIM-1, ICAM-1 and vWF, decreased CD31 expression, elevated serum levels of SDC-1 and HS, increased vascular permeability, and higher expression of TNF-α, IL-1β and IL-6. Compared with the IRI group, the IRI+SDX group showed reduced renal tissue injury, lower tubular injury scores, decreased expression of KIM-1, ICAM-1 and vWF, increased CD31 expression, lower serum levels of SDC-1 and HS, decreased vascular permeability, and reduced expression of TNF-α, IL-1β and IL-6 (all P < 0.05). Ten days after reperfusion, renal tissue injury was further alleviated in the IRI+SDX group. Twenty-five days after reperfusion, the IRI+SDX group exhibited decreased expression of TGF-β, α-SMA, and COL-1, as well as reduced collagen deposition area (all P < 0.05). Compared with the HOPE group, the HOPE+SDX group showed increased renal perfusion flow and decreased intrarenal vascular resistance (both P < 0.01). Conclusions Sulodexide may alleviates renal IRI and fibrosis caused by prolonged warm ischemia by inhibiting inflammatory responses and protecting vascular endothelial glycocalyx.

Objective To explore the effects of nicotinamide mononucleotide （NMN） on hypertensive rats. Methods Two rat hypertension models including spontaneously hypertensive rats（SHR）and two-kidney two-clip （2K2C） rats were used to be given single, long-term or lifelong administration of NMN respectively. NMN’s effects were assessed comprehensively by monitoring survival time, blood pressure levels, and the extent of organ damage in hypertensive model rats. Results It was revealed that NMN did not exhibit protective effects in terms of lowering blood pressure levels, reducing organ damage or increasing survival time in hypertensive rats. Conclusion This study suggested that NMN did not demonstrate anti-hypertensive effects in rat hypertension models and could provide valuable insights for future clinical observation on NMN.

Objective:To investigate the clinical characteristics, therapeutic efficacy and prognosis of patients with human immunodeficiency virus (HIV)-associated Hodgkin lymphoma.Methods:A retrospective case series study was conducted. The clinical data of 22 HIV-associated Hodgkin lymphoma patients in Chongqing University Cancer Hospital from December 2013 to June 2022 were retrospectively analyzed. Their clinical features, laboratory results, treatment, and prognosis were analyzed. Kaplan-Meier method was used to perform survival analysis.Results:The age [ M ( Q1, Q3)] of 22 patients was 44 years old (36 years old, 53 years old); 18 cases were male, 4 cases were female; clinical staging was stage Ⅲ in 5 patients and stage Ⅱ in 17 patients. All 22 patients were infected with HIV through sexual transmission, with 10 cases transmitted through man sex with man and 12 cases transmitted through heterosexual transmission. Nine patients were found to be infected with HIV at the time of diagnosis of lymphoma, and 13 patients presented with lymphoma at 22.2 months (12.3 months, 38.4 months) after diagnosis of HIV infection. Of the 22 patients, 3 abandoned treatment; 19 patients were treated with antiretroviral therapy combined with ABVD regimen chemotherapy, 9 patients had complete remission, and 10 patients had partial remission. After follow-up of 46.8 months (24.8 months, 64.5 months), the 5-year progression-free survival rate was 83.9%, and the 5-year overall survival rate was 89.5%. Conclusions:HIV-associated Hodgkin lymphoma exhibits an invasive process in clinical practice, and standardized antiretroviral therapy combined with ABVD regimen chemotherapy can lead to long-term survival for patients.

Objective Evaluation of the efficacy of high-frequency repetitive transcranial magnetic stimulation for chronic disturbance of consciousness after severe craniocerebral injury based on magnetic resonance spectroscopy.Methods The clinical data of 106 patients with chronic disturbance of consciousness after severe craniocerebral injury from January 2018 to December 2022 were retrospectively analyzed,and they were divided into control group(conventional rehabilitation treatment)and observation group(high frequency repetitive transcranial magnetic stimulation treatment)by propensity score matching method(1∶1),with 53 cases in each group.Both groups were examined by magnetic resonance spectroscopy(MRS)before and after treatment.The brain metabolic indexes[N-acetyl aspartate(NAA)/creatine(Cr)value,choline complex(Cho)/Cr value],Glasgow coma scale(GCS)score,electroencephalogram(EEG)grading,coma recovery scale(CRS-R)score,brainstem auditory evoked potential(BAEP)grading,upper limb sensory evoked potential(SSEP)grading and Cerebral blood flow perfusion index[cerebral blood volume(CBV),mean transit time(MTT),cerebral blood flow(CBF)]were compared between the two groups.Results After treatment,the NAA/Cr values of the thalamus and brainstem in the two groups increased,while the Cho/Cr values decreased,and the levels of brain metabolic indexes in the observation group were signifi-cantly better than those in the control group(P<0.05).The two groups'GCS score and CRS-R score increased,and the improvement of the observation group was better than that of the control group(P<0.05).The BAEP grading,EEG grading,and SSEP grading of the two groups improved,and those of the observation group were better than the control group(P<0.05).The CBF and CBV of the two groups increased,and MTT decreased,and the level of cere-bral blood perfusion index in the observation group was better than that in the control group(P<0.05).Conclusion High frequency repetitive transcranial magnetic stimulation has a significant effect on the recovery of patients with chronic consciousness disorders after severe craniocerebral injury.The mechanism may be related to improving the blood flow velocity of brain tissue and metabolism in the brain.

Objective To generate mice with whole-body overexpression of human METRNL gene.Methods Based on Cre-loxP system,Dppa3-Cre mice were mated with Rosa26-LSL-METRNL knock-in mice(R26-LSL-METRNL+/-)to generate R26-L-METRNL+/-mice.The genotypes of the offsprings were identified,and tissues of the blood,heart,liver,spleen,lung,kidney,brain,white adipose and muscle were collected.The expression of human METRNL gene in mice was investigated by quantitative real-time PCR,western blot and enzyme linked immunosorbent assay.Results Compared with wild type control mice,human METRNL in R26-L-METRNL+/-mice significantly expressed at both mRNA and protein levels in tissues,with abundant METRNL protein in blood.Conclusion The mouse model overexpressing human METRNL gene(R26-L-METRNL+/-mouse)was successfully constructed.

Objective To study the effect of MT-1207 on blood glucose,blood lipids and atherosclerosis in mice.Methods The apolipoprotein E knockout(ApoE-/-)mice were fed with normal feed,drug feed containing losartan and drug feed containing MT-1207 at a dosage of 30 mg/kg.The body weight,blood glucose and blood lipids were detected,and the plaque area of atherosclerotic was evaluated.8-week-old male C57 mice were fed a high fat diet and given intragastric administration of MT-1207 and losartan at a dose of 30 mg/kg per day.The body weight,blood glucose and lipids levels were also examined to further evaluate the effects of MT-1207 on blood glucose and lipids levels.Results ApoE-/-mice treated with MT-1207 and losartan gained weight faster.There was no significant improvement in blood glucose and lipid levels,and no significant change in atherosclerotic plaque area.MT-1207 and losartan had no significant improvement effect on blood glucose and blood lipids of C57 mice.Conclusion MT-1207 and losartan couldn't improve the levels of blood glucose,blood lipids and atherosclerosis,and couldn't aggravate atherosclerosis.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Objective To analyze the perioperative outcomes of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection. Methods The perioperative clinical data of patients receiving heart valve replacement in the Department of Cardiovascular Surgery, the First Affiliated Hospital of University of Science and Technology of China from November 2022 to February 2023 were retrospectively analyzed. According to whether the patients were infected with SARS-CoV-2, they were divided into a non-infected group and an asymptomatic group. The perioperative data of the patients were compared between the two groups, and the effect of asymptomatic infection on the result of heart valve replacement surgery was analyzed. Results A total of 66 patients were enrolled including 36 males and 30 females with a mean age of 58.0±11.1 years. There were 51 patients in the non-infected group and 15 patients in the asymtomatic group. There were 2 patients of mitral valve replacement, 20 patients of aortic valve replacement, 1 patient of double valve replacement, 3 patients of aortic valve replacement with tricuspid valvoplasty, 22 patients of mitral valve replacement and tricuspid valvoplasty, 18 patients of double valve replacement and tricuspid valvoplasty. Asymptomatic infected patients received more emergency surgery than uninfected patients (26.7% vs. 0.0%, P<0.01). There was no statistical difference in the duration of extracorporeal circulation, aortic occlusion, mechanical ventilation time after the surgery, ICU stay, postoperative drainage volume, or postoperative complications between the two groups. Conclusion Perioperative results of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection and non-infection are almost the same.

Thyroid eye disease (TED) is an orbital disease closely associated with thyroid disorders, with 25%-50% of patients with diffuse toxic goiter (Graves Disease) developing secondary TED, which can lead to blindness and disability and significantly impair patients' visual function and quality of life.Activity staging is a crucial assessment index for TED and is essential for clinical evaluation, treatment planning, and prognosis.The Clinical Activity Score (CAS) is currently the most widely used method for this purpose both domestically and internationally.To improve the accuracy and consistency of CAS evaluations, the European Group of Graves' Orbitopathy (EUGOGO) recommended the use of a CAS scoring atlas in the TED guidelines.However, existing atlases are primarily based on Caucasians.Considering the anatomical differences in the orbit between Chinese and Caucasians and the resulting divergent ocular characteristics, there is a need for a comprehensive interpretation of the CAS scoring details in the current guidelines.This should be followed by further refinement to tailor the CAS scoring criteria to Chinese patients with TED.Such measures will standardize the operational methods and judgment criteria of CAS scoring in China, thereby providing a reliable basis for the accurate diagnosis and treatment of the disease.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.