To investigate the association between obesity-related metabolic indices and the risk of knee osteoarthritis(KOA) in middle-aged and older Chinese adults(≥45 years) using data from the China Health and Retirement Longitudinal Study(CHARLS).

Objective:To determine the safety and efficacy of the modified off-pump biatrial mini-maze procedure to treat isolated atrial fibrillation.Methods:This study retrospectively included isolated atrial fibrillation patients who underwent the modified off-pump biatrial mini-maze procedure at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University from January 2021 to December 2023. These patients underwent a mini-maze procedure using the Dallas lesion set protocol. A purse-string suture was then performed on the right atrium, and 4 ablation lesions were made to the superior vena cava, the inferior vena cava, the appendix of the right atrium and the tricuspid valve annulus from the purse-string suture point using the bipolar radiofrequency clamp. After the operation, the patients were followed up at 3, 6 and 12months and every year thereafter.Results:A total of 301 patients were followed up. There were no deaths or strokes. A follow-up at intervals of 3, 6, 12, 24 and 36 months showed that the cumulative success rate free from isolated atrial fibrillation was 96.0%、91.0%、85.9%、79.5% and 72.7%.Conclusion:The modified off-pump biatrial mini-maze procedure is safe and effective and can be considered as an off-pump ablation option for patients and cardiac surgeons.

Objective:To determine the safety and efficacy of the modified off-pump biatrial mini-maze procedure to treat isolated atrial fibrillation.Methods:This study retrospectively included isolated atrial fibrillation patients who underwent the modified off-pump biatrial mini-maze procedure at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University from January 2021 to December 2023. These patients underwent a mini-maze procedure using the Dallas lesion set protocol. A purse-string suture was then performed on the right atrium, and 4 ablation lesions were made to the superior vena cava, the inferior vena cava, the appendix of the right atrium and the tricuspid valve annulus from the purse-string suture point using the bipolar radiofrequency clamp. After the operation, the patients were followed up at 3, 6 and 12months and every year thereafter.Results:A total of 301 patients were followed up. There were no deaths or strokes. A follow-up at intervals of 3, 6, 12, 24 and 36 months showed that the cumulative success rate free from isolated atrial fibrillation was 96.0%、91.0%、85.9%、79.5% and 72.7%.Conclusion:The modified off-pump biatrial mini-maze procedure is safe and effective and can be considered as an off-pump ablation option for patients and cardiac surgeons.

Objective:To preliminarily investigate the safety and efficacy of Pipeline embolization device (PED) in the treatment of unruptured intracranial vertebral artery dissecting aneurysm (VADA).Methods:Patients with unruptured intracranial VADA received PED treatment in the Department of Neurosurgery, Xi'an Ninth Hospital from December 2015 to September 2023 were included retrospectively. Their demographic data, vascular risk factors, clinical symptoms, preoperative modified Rankin Scale (mRS) scores, imaging data, and treatment regime were collected. The O'Kelly-Marotta (OKM) grading scale was used to evaluate the occlusion of aneurysms.Results:A total of 18 patients with unruptured intracranial VADA were enrolled, including 12 males (66.7%), aged 37-67 years. All patients successfully completed PED implantation without any periprocedural complications. Six patients (33.3%) were treated with coil-assisted embolization, and 12 (66.7%) were treated with PED implantation alone. Digital subtraction angiography (DSA) showed contrast retention in aneurysm lumen in 10 patients (55.6%) immediately after surgery. Clinical follow-up was performed in 18 patients, of which the mRS score was 0 in 12 patients (66.7%) and the mRS score was 1 in 6 patients (33.3%). Fifteen patients (88.3%) received DSA follow-up, including 12 (80.0%) with OKM grade D and 3 (20.0%) with grade C, and the posterior inferior cerebellar arteries had smooth blood flow.Conclusion:PED is safe and effective in the treatment of unruptured intracranial VADA.

Objective The CRISPR/Cas9 system was utilized to generate an Apoe knockout mice model to support further investigations of the role of Apoe in lipid metabolism and atherosclerosis.Methods Two single guide RNAs designed for Apoe in C57BL/6J mice were co-injected with Cas9 mRNA into fertilized eggs,followed by transplantation into ICR recipient mice to obtain F0 generation mice.KO mice were identified by polymerase chain reaction(PCR)screening of tail DNA.Apoe mRNA expression in various tissues was assessed by quantitative real-time PCR and lipid indexes were measured in serum samples.Lipid accumulation in the inner lining of aortic vessels was detected by oil red O staining.Results PCR and sequencing confirmed the successful construction of Apoe KO mice(C57BL/6-Apoeem1/Nifdc).Apoe mRNA levels were significantly reduced in the liver,brain,spleen,kidney,and lung tissues of Apoe KO homozygous mice(Apoe-/-),as shown by reverse transcription quantitative real-time PCR.Serum total cholesterol and low-density lipoprotein cholesterol levels were increased in Apoe-/-mice,and high-density lipoprotein cholesterol levels were decreased in male Apoe-/-mice.Extensive lipid plaques were observed in the inner lining of the arteries in Apoe-/-mice compared with WT mice,under normal chow consumption conditions.Conclusions This study successfully established an Apoe KO mice model exhibiting a typical abnormal lipid metabolism phenotype with arterial lipid accumulation,even without a high-fat diet intervention.This work provides background data for the Apoe KO mice resource and a new model for the study of abnormal lipid metabolism.

Objective We generated ob mice(C57BL/6N-Lepem1/Nifdc)with Lep gene knockout(ob/ob)using the CRISPR/Cas9 system,to establish a suitable animal model for preclinical drug evaluation for clinical diseases such as diabetes.Methods According to the principle of CRISPR/Cas9 target design,single guide RNA targeting the mouse Lep gene was designed for transcription in vitro,and microinjected with Cas9 mRNA into mouse zygotes.Mouse tail DNA was extracted and detected by polymerase chain reaction and sequencing,followed by mating of positive and wild-type mice.Blood biochemistry and liver pathology were assessed in homozygous ob mice.Results Eight positive mice were identified and a stable mouse strain was selected for further breeding.Serum triglycerides,total cholesterol,and alanine aminotransferase levels were significantly higher in homozygous ob mice than in wild-type mice,and liver pathology showed inflammatory infiltration and lipid vacuolar transformations.Conclusions We successfully established a Lep gene knockout mouse model,which will provide an important addition to the national rodent experimental animal database and an animal model for preclinical drug evaluation.

Objective The CRISPR/Cas9 system was utilized to generate an Apoe knockout mice model to support further investigations of the role of Apoe in lipid metabolism and atherosclerosis.Methods Two single guide RNAs designed for Apoe in C57BL/6J mice were co-injected with Cas9 mRNA into fertilized eggs,followed by transplantation into ICR recipient mice to obtain F0 generation mice.KO mice were identified by polymerase chain reaction(PCR)screening of tail DNA.Apoe mRNA expression in various tissues was assessed by quantitative real-time PCR and lipid indexes were measured in serum samples.Lipid accumulation in the inner lining of aortic vessels was detected by oil red O staining.Results PCR and sequencing confirmed the successful construction of Apoe KO mice(C57BL/6-Apoeem1/Nifdc).Apoe mRNA levels were significantly reduced in the liver,brain,spleen,kidney,and lung tissues of Apoe KO homozygous mice(Apoe-/-),as shown by reverse transcription quantitative real-time PCR.Serum total cholesterol and low-density lipoprotein cholesterol levels were increased in Apoe-/-mice,and high-density lipoprotein cholesterol levels were decreased in male Apoe-/-mice.Extensive lipid plaques were observed in the inner lining of the arteries in Apoe-/-mice compared with WT mice,under normal chow consumption conditions.Conclusions This study successfully established an Apoe KO mice model exhibiting a typical abnormal lipid metabolism phenotype with arterial lipid accumulation,even without a high-fat diet intervention.This work provides background data for the Apoe KO mice resource and a new model for the study of abnormal lipid metabolism.

Objective We generated ob mice(C57BL/6N-Lepem1/Nifdc)with Lep gene knockout(ob/ob)using the CRISPR/Cas9 system,to establish a suitable animal model for preclinical drug evaluation for clinical diseases such as diabetes.Methods According to the principle of CRISPR/Cas9 target design,single guide RNA targeting the mouse Lep gene was designed for transcription in vitro,and microinjected with Cas9 mRNA into mouse zygotes.Mouse tail DNA was extracted and detected by polymerase chain reaction and sequencing,followed by mating of positive and wild-type mice.Blood biochemistry and liver pathology were assessed in homozygous ob mice.Results Eight positive mice were identified and a stable mouse strain was selected for further breeding.Serum triglycerides,total cholesterol,and alanine aminotransferase levels were significantly higher in homozygous ob mice than in wild-type mice,and liver pathology showed inflammatory infiltration and lipid vacuolar transformations.Conclusions We successfully established a Lep gene knockout mouse model,which will provide an important addition to the national rodent experimental animal database and an animal model for preclinical drug evaluation.

ObjectiveThrough improving the potential of vascular endothelial growth factor receptor (VEGFR)-humanized mouse model (hKDR^+/+) with C57BL/6N background to allow the growth of different mouse tumor cell lines, to establish novel tumor-bearing mouse models which can support in vivo tumorigenesis of different mouse tumor cell lines and be used to evaluate drugs targeting VEGFR.MethodsFirstly, a method to evaluate the in vivo activity of antibody targeting VEGFR based on the hKDR^+/+ humanized mouse model was established. Recombinant activating gene 1 (Rag1) knockout mice (Rag1^-/-) were established using CRISPR/Cas9 technology. Then these Rag1^-/- mice were crossed with hKDR^+/+ mice to get a double gene modified homozygous hKDR^+/+/Rag1^-/- mouse model by screening. Finally, tumor cell lines derived from different mouse strains were tested on the double gene-modified mouse model to compare the differences in tumor growth. ResultsAntibodies designed for VEGFR showed significant anti-tumor activity in hKDR^+/+ mice, which significantly reduced tumor volume and weight compared with the PBS group (P<0.01, P<0.05). The number of B cells and T cells in the peripheral blood of Rag1^-/- mice and hKDR^+/+/Rag1^-/- mice decreased (P<0.05, P<0.001). Tumors were observed in hKDR^+/+/Rag1^-/-, Rag1^-/-, wild-type, and hKDR^+/+ mice after 7 d of inoculation of MC38 cells derived from C57BL/6 mice. Tumors were only observed in groups of hKDR^+/+/Rag1^-/- and Rag1^-/- mice, but not in the wild-type and hKDR^+/+ mice after 10 d of inoculation with CT26 cells derived from BALB/c mice. After 3 weeks of inoculation, the tumor volume of hKDR^+/+/Rag1^-/- mice was significantly larger than that of Rag1^-/- mice (P<0.01). ConclusionRag1 knockout mice were obtained and a novel hKDR^+/+/Rag1^-/- double genes modified mouse model was further screened. The tumor cell lines from different mouse strain origins were more prone to growth in mice with Rag1 gene deficiency. The results suggest that the reduced immune response of hKDR^+/+ humanized mice will improve the capacity of supporting the growth of mouse tumor lines in the model. As a result, more tumor-bearing mouse models may be constructed for the evaluation of drugs targeting VEGFR in this way.

OBJECTIVES: Intrauterine adhesions (IUA) refers to the adhesions between the myometrium of the uterine cavity, which is secondary to damage to the basal layer of the endometrium due to trauma or infection. The occurrence of IUA is mainly related to intrauterine operations. Hysteroscopic adhesiolysis (HA) is the standard surgical treatment for IUA. But the recurrence rate of IUA after HA is still high. Importantly, endometrium recovery is difficult, resulting in unsatisfied prognosis for moderate to severer IUA patients. Therefore, it is important to take effective primary preventive measures against the etiology to avoid endometrium damage from medical surgery. In this paper, we discuss and analyze predilection and severer sites of intrauterine adhesions, aiming to provide a basis for how to avoid and reduce injuries during intrauterine operations, such as abortion, dilation and curettage. METHODS: In this study, we retrospectively analyzed the surgical videos of patients who underwent HA for the first time from January 2019 to December 2021 in the Third Xiangya Hospital of Central South University so as to assess the area of adhesions and predilection and severer sites of occurrence of adhesions, and we collected 657 patients who underwent HA for the first time, including 81 patients with total IUA and 576 patients with partial IUA. We counted and analyzed the number and composition ratio of partial IUA patients with severer sites of damage to the lateral wall of the uterine cavity and severerr sites of damage to each segment of the uterine cavity. RESULTS: Among 576 patients with partial IUA, there were 60 patients with no significant difference in the degree of adhesions between the right and left sides, 143 patients with severer adhesions on the left side of the uterine cavity, and 373 patients with severer adhesions on the right side of the uterine cavity. There was a difference in the severity of damage of left and right lateral wall. The proportion of patients with severer adhesions on the right side of the uterine cavity (64.8%) was higher than that of patients with adhesions on the left side of the uterine cavity (24.8%), and there was statistically difference (P<0.05). There was 93 patients with severer adhesions at the fundus or bilateral horn of the uterus, 190 patients with severer adhesions at the middle and upper part of the uterine cavity, 245 patients with severer adhesions at the middle and lower part of the uterine cavity and at the endocervix, and 48 patients with no significant difference in the degree of adhesions in each part. The proportion of patients with severer adhesions at the middle and lower part of the uterine cavity and at the endocervix was higher (42.5%) than those with adhesions in the fundus or bilateral horn of the uterus (16.1%) and in the middle and upper part of the uterine cavity (33.0%), and there were statistically differences (both P<0.05). CONCLUSIONS The predilection site of IUA is the lateral wall of the uterine cavity. The severer adhesions is in the right lateral wall of the uterine cavity, the middle and lower segments and the endocervix, which may be related to the operating habits of the surgeon. Therefore, gynecologists should minimize damage to the lateral wall of the uterine cavity, especially the right lateral wall in performing uterine operations (more attention should be paid by right-handed physicians). Besides, we should pay attention to protecting the middle and lower segments of the uterine cavity and the endocervix, avoiding maintaining negative pressure to withdraw the uterine tissue suction tube from the uterine cavity during abortion procedures to minimize damage.
Humans ; Retrospective Studies ; Tissue Adhesions ; Uterus/pathology*