Objective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease(NAFLD)and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group(Chow group)and a methionine-choline-deficient(MCD)diet group(MCD group),with 10 mice per group.The MCD diet was used to induce NAFLD.Each group was further divided into two subgroups,resulting in four subgroups:Chow+saline,Chow+liraglutide,MCD+saline,and MCD+liraglutide group.After daily intraperitoneal injection of liraglutide(400 μg/kg)or an equivalent volume of saline for 4 weeks,an intraperitoneal glucose tolerance test(IPGTT)was performed.Serum levels of aspartate transaminase(AST),alanine aminotransferase(ALT),total cholesterol(TC),triglyceride(TAG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured.Liver tissues were collected post-euthanasia to assess TAG content.Histopathological changes,lipid deposition,and fibrosis were evaluated via hematoxylin-eosin(HE)staining,Oil Red O staining,and Masson staining.Real-time quantitative PCR(qPCR)and Western blotting were used to analyze the expression of α-smooth muscle actin(α-SMA),fibronectin(FN),collagen type Ⅰ α(COL1A),matrix metalloproteinase 9(MMP9),tissue inhibitor of metalloproteinase 1(TIMP1),transforming growth factor β(TGF-β),SMAD3,and phosphorylated SMAD3(pSMAD3).Results·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15,30,and 60 min,with a decreased area under the curve(AUC)(both P<0.05).Biochemical analysis showed that liraglutide lowered AST and ALT levels(both P<0.001),increased TC and HDL-C levels(both P<0.05),but had no significant effect on TAG or LDL-C in MCD mice.HE staining and Oil Red O staining revealed reduced lipid droplets,ballooning degeneration,and inflammatory infiltration in hepatocytes after liraglutide treatment.Masson staining indicated decreased collagen fiber deposition in the liver.qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3,alongside downregulated MMP9 in MCD mice.Liraglutide reversed these changes,lowering α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3 expression while increasing MMP9 expression.Conclusion·Liraglutide ameliorates liver injury,lipid deposition,and fibrosis in NAFLD mice,through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression.

The overall incidence of lymphomas associated with HIV infection is low, and only few hematological oncology specialties provide standardized treatment. Newly diagnosed patients with impaired immune function have a high incidence of complications, such as infections during induction chemotherapy, which increases treatment difficulties. For patients with relapse/refractory status, salvage treatment options are extremely limited, because new drug clinical trials are lacking. At present, both domestic and international clinical practices have shown that patients with lymphomas associated with HIV infection can achieve long-term survival after standardized combination antiretroviral therapy (cART) with targeted immunochemotherapy, followed by autologous hematopoietic stem cell transplantation (auto-HSCT) immediately after achieving complete remission. In recent years, some new drugs, such as XPO1 inhibitors, immune checkpoint inhibitors, antibody-drug conjugates (ADC drugs), bispecific antibodies, and small-molecule drugs, have been tentatively incorporated into treatment regimens for patients with lymphomas associated with HIV infection, and preliminary clinical data have been obtained. Based on two patients with lymphomas associated with HIV infection who were admitted to our center, this study proposed a standardized diagnostic and treatment pathway and provided corresponding references for clinicians to apply new drugs. The aim of this study was to promote diagnostic and treatment capabilities and improve the survival and quality of life of patients of lymphomas associated with HIV infection in China.

The overall incidence of lymphomas associated with HIV infection is low, and only few hematological oncology specialties provide standardized treatment. Newly diagnosed patients with impaired immune function have a high incidence of complications, such as infections during induction chemotherapy, which increases treatment difficulties. For patients with relapse/refractory status, salvage treatment options are extremely limited, because new drug clinical trials are lacking. At present, both domestic and international clinical practices have shown that patients with lymphomas associated with HIV infection can achieve long-term survival after standardized combination antiretroviral therapy (cART) with targeted immunochemotherapy, followed by autologous hematopoietic stem cell transplantation (auto-HSCT) immediately after achieving complete remission. In recent years, some new drugs, such as XPO1 inhibitors, immune checkpoint inhibitors, antibody-drug conjugates (ADC drugs), bispecific antibodies, and small-molecule drugs, have been tentatively incorporated into treatment regimens for patients with lymphomas associated with HIV infection, and preliminary clinical data have been obtained. Based on two patients with lymphomas associated with HIV infection who were admitted to our center, this study proposed a standardized diagnostic and treatment pathway and provided corresponding references for clinicians to apply new drugs. The aim of this study was to promote diagnostic and treatment capabilities and improve the survival and quality of life of patients of lymphomas associated with HIV infection in China.

Objective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease(NAFLD)and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group(Chow group)and a methionine-choline-deficient(MCD)diet group(MCD group),with 10 mice per group.The MCD diet was used to induce NAFLD.Each group was further divided into two subgroups,resulting in four subgroups:Chow+saline,Chow+liraglutide,MCD+saline,and MCD+liraglutide group.After daily intraperitoneal injection of liraglutide(400 μg/kg)or an equivalent volume of saline for 4 weeks,an intraperitoneal glucose tolerance test(IPGTT)was performed.Serum levels of aspartate transaminase(AST),alanine aminotransferase(ALT),total cholesterol(TC),triglyceride(TAG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured.Liver tissues were collected post-euthanasia to assess TAG content.Histopathological changes,lipid deposition,and fibrosis were evaluated via hematoxylin-eosin(HE)staining,Oil Red O staining,and Masson staining.Real-time quantitative PCR(qPCR)and Western blotting were used to analyze the expression of α-smooth muscle actin(α-SMA),fibronectin(FN),collagen type Ⅰ α(COL1A),matrix metalloproteinase 9(MMP9),tissue inhibitor of metalloproteinase 1(TIMP1),transforming growth factor β(TGF-β),SMAD3,and phosphorylated SMAD3(pSMAD3).Results·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15,30,and 60 min,with a decreased area under the curve(AUC)(both P<0.05).Biochemical analysis showed that liraglutide lowered AST and ALT levels(both P<0.001),increased TC and HDL-C levels(both P<0.05),but had no significant effect on TAG or LDL-C in MCD mice.HE staining and Oil Red O staining revealed reduced lipid droplets,ballooning degeneration,and inflammatory infiltration in hepatocytes after liraglutide treatment.Masson staining indicated decreased collagen fiber deposition in the liver.qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3,alongside downregulated MMP9 in MCD mice.Liraglutide reversed these changes,lowering α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3 expression while increasing MMP9 expression.Conclusion·Liraglutide ameliorates liver injury,lipid deposition,and fibrosis in NAFLD mice,through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression.

Objective:To analyze the consistency between MT-9000 and IOLMaster 700 in measuring preoperative ocular biometric parameters in patients with age-related cataracts.Methods:A cross-sectional study was conducted.A total of 536 patients (536 eyes) were consecutively included and scheduled for cataract extraction combined with intraocular lens implantation at Aier Eye Hospital of Wuhan University from June 20 to August 22, 2024.Two visualized sweep-frequency biometers, MT-9000 and IOLMaster 700, were used to measure the biometric parameters of all the patients.The parameters including axial length (AL), white to white (WTW), anterior chamber depth (ACD), lens thickness (LT), central corneal thickness (CCT), and mean keratometry (Km). The AL detection rates of the two instruments were compared, as were the differences in above parameters, and the correlation and consistency of the measurements were analyzed.Patients were divided into three groups based on AL measured by MT-9000: a short axis group (AL<22 mm) comprising 27 eyes, a normal axis group (22≤AL≤25 mm) comprising 392 eyes, and a long axis group (AL>25 mm) comprising 104 eyes.The differences in measured AL in different subgroups were compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Aier Eye Hospital, Wuhan University (No.2024IRB06017). Written informed consent was obtained from each subject.Results:The AL detection rate measured by MT-9000 was 99.3% (532/536), higher than 97.6% (523/536) measured by IOLMaster 700, with a statistically significant difference ( χ2=4.841, P=0.028). MT-9000 AL, LT and Km measurements were all higher than IOLMaster 700 measurements, showing statistically significant differences ( Z=6.418, t=4.971, 5.179; all P<0.001). WTW and CCT measurements from MT-9000 were both lower than those from IOLMaster 700, showing statistically significant differences ( Z=-3.017, t=16.322; both P<0.05). After grouping based on AL measurements from MT-9000, there was no statistically significant differences in AL measurements between MT-9000 and IOLMaster 700 in the short axis group and the normal axis group ( Z=-1.530, P=0.126; t=-0.880, P=0.380). In the long axis group, the AL measured by MT-9000 was longer than that by IOLMaster 700, with a statistically significant difference ( Z=7.254, P<0.001). The intra-class correlation coefficient values of AL, WTW, ACD, LT, CCT, and Km measured by MT-9000 and IOLMaster 700 were 1.000, 0.616, 0.997, 0.999, 0.988, and 0.995 (all P<0.001), respectively.The 95% limits of agreement (LoA) of AL, WTW, ACD, LT, CCT, and Km measured by Bland-Altman analysis were -0.06-+ 0.08 mm, -0.64-+ 0.57 mm, -0.06-+ 0.06 mm, -0.04-+ 0.05 mm, -13.6-+ 6.3 μm and -0.26-+ 0.32 D, respectively, which had 6.5%, 3.6%, 5.3%, 6.3%, 6.5% and 4.4% of the data points outside the 95% LoA. Conclusions:MT-9000 shows favorable agreement with IOLMaster 700 in the measurement of AL, ACD, LT, CCT and Km.MT-9000 is suitable for preoperative biometrics measurement in cataract patients.However, the agreement between the two devices is not desirable in the measurement of WTW, and interchangeable use of these two devices is not recommended in this regard.Additionally, MT-9000 outperforms IOLMaster 700 in terms of AL detection rate.

Objective:To analyze the consistency between MT-9000 and IOLMaster 700 in measuring preoperative ocular biometric parameters in patients with age-related cataracts.Methods:A cross-sectional study was conducted.A total of 536 patients (536 eyes) were consecutively included and scheduled for cataract extraction combined with intraocular lens implantation at Aier Eye Hospital of Wuhan University from June 20 to August 22, 2024.Two visualized sweep-frequency biometers, MT-9000 and IOLMaster 700, were used to measure the biometric parameters of all the patients.The parameters including axial length (AL), white to white (WTW), anterior chamber depth (ACD), lens thickness (LT), central corneal thickness (CCT), and mean keratometry (Km). The AL detection rates of the two instruments were compared, as were the differences in above parameters, and the correlation and consistency of the measurements were analyzed.Patients were divided into three groups based on AL measured by MT-9000: a short axis group (AL<22 mm) comprising 27 eyes, a normal axis group (22≤AL≤25 mm) comprising 392 eyes, and a long axis group (AL>25 mm) comprising 104 eyes.The differences in measured AL in different subgroups were compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Aier Eye Hospital, Wuhan University (No.2024IRB06017). Written informed consent was obtained from each subject.Results:The AL detection rate measured by MT-9000 was 99.3% (532/536), higher than 97.6% (523/536) measured by IOLMaster 700, with a statistically significant difference ( χ2=4.841, P=0.028). MT-9000 AL, LT and Km measurements were all higher than IOLMaster 700 measurements, showing statistically significant differences ( Z=6.418, t=4.971, 5.179; all P<0.001). WTW and CCT measurements from MT-9000 were both lower than those from IOLMaster 700, showing statistically significant differences ( Z=-3.017, t=16.322; both P<0.05). After grouping based on AL measurements from MT-9000, there was no statistically significant differences in AL measurements between MT-9000 and IOLMaster 700 in the short axis group and the normal axis group ( Z=-1.530, P=0.126; t=-0.880, P=0.380). In the long axis group, the AL measured by MT-9000 was longer than that by IOLMaster 700, with a statistically significant difference ( Z=7.254, P<0.001). The intra-class correlation coefficient values of AL, WTW, ACD, LT, CCT, and Km measured by MT-9000 and IOLMaster 700 were 1.000, 0.616, 0.997, 0.999, 0.988, and 0.995 (all P<0.001), respectively.The 95% limits of agreement (LoA) of AL, WTW, ACD, LT, CCT, and Km measured by Bland-Altman analysis were -0.06-+ 0.08 mm, -0.64-+ 0.57 mm, -0.06-+ 0.06 mm, -0.04-+ 0.05 mm, -13.6-+ 6.3 μm and -0.26-+ 0.32 D, respectively, which had 6.5%, 3.6%, 5.3%, 6.3%, 6.5% and 4.4% of the data points outside the 95% LoA. Conclusions:MT-9000 shows favorable agreement with IOLMaster 700 in the measurement of AL, ACD, LT, CCT and Km.MT-9000 is suitable for preoperative biometrics measurement in cataract patients.However, the agreement between the two devices is not desirable in the measurement of WTW, and interchangeable use of these two devices is not recommended in this regard.Additionally, MT-9000 outperforms IOLMaster 700 in terms of AL detection rate.

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 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 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.