Osteoarthritis (OA) is a common chronic degenerative disease of joints, which is one of the main causes of chronic pain and disability. Several studies have shown that OA is causally associated with many factors, such as cytokines, metabolic diseases, nutrients, gut microbiota, and life behaviors. The risk factors included obesity, hyperlipidemia and bone mineral density, and the protective factors included the use of potassium-sparing diuretics and aldosterone antagonists, folic acid and arginine. These factors influence the progression of OA mainly by participating in the body's inflammatory response and material metabolic processes or by altering the biomechanics of weight-bearing joints. In addition, the chronic pain symptoms of OA, the expression of inflammatory factors, and the use of non-steroidal anti-inflammatory drugs may increase the risk of other diseases, such as type 2 diabetes, severe depression, and Parkinson's disease. Mendelian randomization is a new method to explore the causal association between diseases and risk factors. This method uses the random allocation of genetic variants to simulate randomized controlled trials and uses the instrumental variables related to risk factors and diseases to test the causal association between them. This review included the Mendelian randomization-related studies of OA and analyzed the causal association between OA and metabolic diseases, cardiovascular diseases, musculoskeletal diseases, central nervous system diseases, psychiatric diseases, cytokines, metabolomics, nutrients, gut microbiota, life behavior, telomere length and mitochondrial heterogeneity, which is of great significance for the prevention and treatment of OA.

Objective To investigate the effectiveness and safety of coaxial catheter technique in carotid artery stent implantation via radial artery approach.Methods The general and clinical data of patients,who underwent carotid artery stent implantation via radial artery approach at the Department of Neurology,Daxing Teaching Hospital of Capital Medical University of China between January 2021 and October 2022,were retrospectively analyzed.During the operation,coaxial catheter technology was used to make a 6F catheter inserting into the target vessel for performing carotid stent implantation,and the rate of successful catheter placement,surgical success rate,and perioperative complications were analyzed.Results A total of 40 patients,who underwent carotid artery stent implantation via radial artery approach,were enrolled in this study.The involved vessels included left internal carotid artery(n=16),right internal carotid artery(n=24),type Ⅰaortic arch(n=13),type Ⅱ aortic arch(n=20),type Ⅲ aortic arch(n=7),and bovine aortic arch(n=1).The rate of successful catheter placement was 100％,the surgical success rate was 95％,and no procedure-related complications occurred.The time spent on surgery was(34.4±13.6)min.No patients developed symptoms of cerebral infarction or myocardial infarction in 30 days after the operation.Conclusion The use of coaxial catheter technology can make the catheter inserting into the target vessel quickly and avoid repeated catheter exchange.Coaxial catheter technology is safe and effective in performing carotid artery stent implantation via radial artery approach.(J Intervent Radiol,2023,32:1169-1173)

Background::Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies.Methods::Seven patients with UC were included who underwent curative surgery at our hospital between July 2020 and October 2020. We performed single-cell RNA sequencing (scRNA-seq) analysis in seven tumors with six matched adjacent normal tissues and integrated the results with two public scRNA-seq datasets. The functional properties and intercellular interactions between single cells were characterized, and the results were validated using multiplex immunofluorescence staining, flow cytometry, and bulk transcriptomic datasets. All statistical analyses were performed using the R package with two-sided tests. Wilcoxon-rank test, log-rank test, one-way analysis of variance test, and Pearson correlation analysis were used properly.Results::Unsupervised t-distributed stochastic neighbor embedding clustering analysis identified ten main cellular subclusters in urothelial tissues. Of them, seven urothelial subtypes were noted, and malignant urothelial cells were characterized with enhanced cellular proliferation and reduced immunogenicity. CD8 + T cell subclusters exhibited enhanced cellular cytotoxicity activities along with increased exhaustion signature in UC tissues, and the recruitment of CD4 + T regulatory cells was also increased in tumor tissues. Regarding myeloid cells, coordinated reprogramming of infiltrated neutrophils, M2-type polarized macrophages, and LAMP3 + dendritic cells contribute to immunosuppressive TME in UC tissues. Tumor tissues demonstrated enhanced angiogenesis mediated by KDR + endothelial cells and RGS5 +/ACTA2 + pericytes. Through deconvolution analysis, we identified multiple cellular subtypes may influence the programmed death-ligand 1 (PD-L1) immunotherapy response in patients with UC. Conclusion::Our scRNA-seq analysis clarified intra-tumoral heterogeneity and delineated the pro-tumoral and immunosuppressive microenvironment in UC tissues, which may provide novel therapeutic targets.

Objective:To analyze the clinical and radiological features of patients with hypoplasia of the internal carotid artery.Methods:Four patients with hypoplasia of the internal carotid artery (including 3 patients with congenital absence of the internal carotid artery), admitted to our hospital from January 2010 to December 2021, were chosen in our study. The clinical data and imaging features of these patients were retrospectively analyzed.Results:The age of these patients ranged from 31 to 73 years, and two patients were female. Clinically,2 patients presented with dizziness, 1 patient presented with limb weakness, and 1 patient was asymptomatic. In 3 patients with congenital absence of the internal carotid artery, DSA results showed that the internal carotid artery was not developed, and CT bone window showed that the internal carotid artery canal was absent; 1 patient with hypoplasia of the internal carotid artery showed thin imaging in DSA results. One patient was combined with anterior communicating artery aneurysm and left internal carotid artery aneurysm. One patient was with vertebral arterial dolichoectasia. The collateral circulation compensation: type A was noted in 3 patients and type C was noted in 1 patient.Conclusion:The patients with hypoplasia of the internal carotid artery are usually asymptomatic, and patients with congenital absence of the internal carotid artery can have ischemic symptom; these patients can be complicated with vascular abnormalities such as aneurysm and vascular thickening.

Objective:To analyze the clinical and radiological features of patients with hypoplasia of the internal carotid artery.Methods:Four patients with hypoplasia of the internal carotid artery (including 3 patients with congenital absence of the internal carotid artery), admitted to our hospital from January 2010 to December 2021, were chosen in our study. The clinical data and imaging features of these patients were retrospectively analyzed.Results:The age of these patients ranged from 31 to 73 years, and two patients were female. Clinically,2 patients presented with dizziness, 1 patient presented with limb weakness, and 1 patient was asymptomatic. In 3 patients with congenital absence of the internal carotid artery, DSA results showed that the internal carotid artery was not developed, and CT bone window showed that the internal carotid artery canal was absent; 1 patient with hypoplasia of the internal carotid artery showed thin imaging in DSA results. One patient was combined with anterior communicating artery aneurysm and left internal carotid artery aneurysm. One patient was with vertebral arterial dolichoectasia. The collateral circulation compensation: type A was noted in 3 patients and type C was noted in 1 patient.Conclusion:The patients with hypoplasia of the internal carotid artery are usually asymptomatic, and patients with congenital absence of the internal carotid artery can have ischemic symptom; these patients can be complicated with vascular abnormalities such as aneurysm and vascular thickening.

Objective:To explore the relationship between the length of cervical spinous process and cervical motion and affected segment of cervical spondylotic myelopathy(CSM).Methods:Retrospective analysis was performed on 375 patients who underwent cervical surgical treatment due to single-segment cervical spondylotic myelopathy from January 2015 to January 2019. There were 200 males and 175 females, aged 50.72±9.39 (range 40 to 60) years. Several parameters, including the sagittal diameter of vertebral body, the sagittal diameter of cervical canal, the length of cervical spinous process, C 3-C 7 lordotic angle, range of motion (ROM) at C 3-C 7 and segmental ROM were measured via preoperative plain radiographs. All parameters were tested via Shapiro-Wilk method. Pearson correlation analyses was used to quantify the relationship between the lengths of C 3-C 7 spinous process and segmental ROMs. Receiver operating characteristic (ROC) curve was mapped to obtain the cut-off points according to the length of cervical spinous process which had significant differences. Patients were divided into two groups based on the cut-off points. χ2 test and t test were used to exclude the interference of age, gender and other anatomical factors and compare the differences in the affected segment of cervical spondylotic myelopathy between groups, so as to analyze the relationship between the length of cervical spinous process and affected segment of cervical spondylotic myelopathy. Results:There were significant differences of C 6 spinous process 27.82±6.01 mm and significantly negative correlation between the length of C 6 spinous process and the ROM at C 6,7 segment ( r=-0.338, P<0.001), while no significant correlations were found in other segments. ROC curves were mapped to obtain the cut-off points, and the cut-off point was 0.76. Group I: the ratio of the length of spinous process of C 6/C 7 (C 6/C 7 ratio, range 0.49 to 1.01) under 0.76, Group II: C 6/C 7 ratio more than 0.76. Compared with patients with longer-type C 6 spinous process (C 6/C 7 ratio ≥0.76), patients with shorter-type C 6 spinous process (C 6/C 7 ratio <0.76) had significantly bigger ROM at C 6,7 segment (10.11° vs 7.10°, P<0.001) and higher incidence of C 6,7 spinal cord compression ( χ2=16.642, P<0.001, OR=2.521), while differences in age, sex, sagittal diameters of vertebral body and spinal canal between two groups were not significant. Conclusion:The length of C 6 spinous process was significantly correlated with ROM at C 6,7 segment and the incidence of C 6,7 degenerative myelopathy. The length of C 6 spinous process can be considered as a predictor of development of C 6,7 degenerative myelopathy.

Objective:To study the relationship between the expression of carnitine palmitoyltransferase 1α (CPT1α) and progression of renal interstitial fibrosis and chronic kidney disease (CKD), and to evaluate the value of CPT1α as a biomarker in pathological diagnosis of renal interstitial fibrosis and CKD.Methods:As a retrospective cohort study, information of CKD patients dignosed with tubulointerstitial fibrosis by renal biopsy and receiving follow-up from March 1, 2010 to July 30, 2017 in the Second Affiliated Hospital of Nanjing Medical University were collected. Renal tissues were stained by immunohistochemistry to detect the expression of CPT1α protein and then divided into three groups according to the quartile of proportion of CPT1α positive staining cells, including group Q1(>67.89%), group Q2(49.84%-67.89%) and group Q3(<49.84%). The degree of renal interstitial fibrosis was measured by Masson staining and lipid deposition was represented by Bodipy staining. Messenger RNA of CPT1α and collagen as well as other extracellular matrix genes were detected by real time-PCR. Relationships between proportion of CPT1α positive staining cells and renal interstitial fibrosis and renal function were analyzed by linear regression analysis. The relationship between CPT1α positive cell number ratio and renal function progression was measured by Pearson correlation analysis and generalized linear model. The effect of lipid-lowering medicine on renal function of CKD patients was analyzed by paired comparative analysis.Results:Ninety patients with CKD were included in this study. Renal interstitial fibrosis and lipid droplets deposition area increased in Q2/Q3 group compared with Q1 group by Masson and Bodipy staining (all P<0.05). Messenger RNA level of extracellular matrix-related proteins increased in Q2/Q3 group by real time-PCR than those of Q1 group (all P<0.05). Linear regression analysis showed that fibrosis area was negatively correlated with the proportion of CPT1α positive staining cells ( r=-0.309, P<0.01). The baseline expression of CPT1α in renal issues was negatively related with serum creatinine (Scr) ( r=-2.801, P<0.001), positively related with estimated glomerular filtration rate (eGFR) ( r=1.240, P<0.001). After a medium follow-up of 3.47 years, CPT1α positive cell number ratio was positively correlated with eGFR change rate by Pearson analysis ( r=0.220, P=0.038). Paired stratified analysis showed that taking lipid-lowering medicines attenuated the decrease of eGFR in Q2 group and Q3 group but not in Q1 group (both P<0.05). Conclusions:The decline of CPT1α in renal tissues of CKD patients is associated with the increase of Scr, the decrease of eGFR and renal interstitial fibrosis. CPT1α is a promising molecular marker to evaluate the degree of renal fibrosis and the progression of CKD.

Objective: To detect norovirus (NoV) GⅠ.1- and GⅡ.4-specific IgG, IgA and histo-blood group antigen (HBGA)-blocking antibodies in healthy populations of all age groups in China for better understanding the epidemiological features of norovirus in China from a serological point of view and providing basic data for vaccine development and clinical trial design. Methods: Indirect ELISA and HBGA-blocking assay were used to detect NoV-specific IgG, IgA and HBGA-blocking antibodies in serum samples collected from healthy natural populations (n=839, aged from six months to 88 years old) in Guangzhou, Fuyang and Yantai. The results were statistically analyzed. Results: The total positive rates of NoV GⅠ.1- and GⅡ.4-specific IgG antibodies were 91.9% and 93.0%. The positive rates of GⅠ.1- and GⅡ.4-specific IgA antibodies were 48.6% and 75.6%, and the titers of HBGA-blocking antibodies to GⅠ.1 and GⅡ.4 norovirus were 5.04 (95%CI: 4.63-5.49) and 18.15 (95%CI: 16.11-20.44). The positive rates of IgG and IgA antibodies generally showed an increasing trend with age. The positive rates of GⅠ.1- and GⅡ.4-specific IgG antibodies ranged from 79.2% to 100.0% and 76.7% to 100.0% in different age groups. They were 81.7% and 85.0% in the age group of 0.5-<1 year, 79.2% and 76.7% in the age group of 1-<2 years, and 98.1% and 96.3% in the age group of 12-<18 years, and maintained at 96% and 98% in the older age groups. The positive rates of GⅠ.1-specific IgA antibody ranged from 11.7% to 93.8% in different age groups and rapidly increased with age. It was 11.7% in the age group of 0.5-<1 year, and reached 93.3% in people aged 45-<60 years and 93.8% in people aged ≥60 years. The positive rates of GⅡ.4-specific IgA antibody ranged from 50.8% to 88.8% in different age groups with 50.8% in people aged 0.5-<1 year, and 86.7%-90.7% in people aged 12-<18 years and older. The titer of GⅠ.1 HBGA-blocking antibody generally increased with age. The antibody titer in populations aged 0.5-<12 years old was lower than that in those aged 18 years and above (GMT: 2.98-4.07 vs 8.21-11.62, P<0.001), and the titer in people of 12-<18 years old was lower than that in those of 45 years old and above (GMT: 5.21 vs 11.03-11.62, P<0.05). No obvious change with age was observed in the titer of GⅡ.4 HBGA-blocking antibody excepting the significant difference between populations of 2-<5 and 22-<45 years old (GMT: 26.73 vs 11.87, P<0.01). Conclusions This study revealed the characteristics of serum NoV GⅠ.1- and GⅡ.4-specific IgG, IgA and HBGA blocking antibodies in populations of different age groups in central and eastern China through analyzing their positive rates and titers and provided preliminary seroepidemiological data for the development of NoV vaccines in China.

OBJECTIVE: To analyze the incidence and risk factors of benign liver space-occupying mass in patients with chronic hepatitis B (CHB) and the ultrasound features that differentiate these masses from small hepatocellular carcinoma. METHODS: We retrospectively analyzed the color Doppler and clinical data of 17 721 patients with CHB treated in the Hepatology Unit of Nanfang Hospital between January, 2016 and December, 2017. The data were compared with those of 21629 healthy control subjects undergoing routine physical examination in the Center of Heath Management of Nanfang Hospital during the same period. RESULTS: Compared with the control subjects, the patients with CHB had significantly higher incidences of hepatic cysts (11.8% 8.7%, < 0.05), hepatic hemangioma (8.2% 1.6%, < 0.05) and hepatic cirrhosis nodules (20.6% 2.4%, < 0.05). The incidences of hepatic cysts and cirrhosis nodules increased with age and was significantly higher in male than in female patients ( < 0.001). The highest incidence of hepatic hemangioma was found in CHB patients aged 30-49 years without a gender difference (>0.05). Sonographically, the benign liver masses commonly showed homogeneous echo within the lesion with clear boundaries and regular shape. Hepatic hemangioma was distinctively hyperechoic in 83.32% (1579/1895) of the patients, while small hepatocellular carcinoma presented with weaker peripheral and internal blood flow signals with a lower flow velocity in the arteries and a higher flow velocity in the portal vein. Liver cirrhosis nodules mostly showed a mixture of strong and weak echoes (79.60%; 7637/9595) without blood flow signal within or around the nodule; an increased volume of the nodule accompanied by heterogeneous echoes within the nodule indicated an increased probability of malignant lesion. Hepatic cysts often displayed no echo within the lesion, but the echo could be enhanced posteriorly. CONCLUSIONS The patients with CHB are at a significantly higher risk of developing hepatic cysts, hepatic hemangiomas and hepatic cirrhosis nodules than the control population, and an older age and the male gender are associated with a higher incidence of hepatic cysts or cirrhosis. The differences in the sonographic and hemodynamic features can help to differentiate hepatic benign mass from malignant lesions, and kinetic changes in sonography can be used to monitor potential malignant transformation of the cirrhotic lesions.

OBJECTIVE: To compare the efficacy and safety of different antiviral and antifibrotic regimens in patients with chronic hepatitis B (CHB) and hepatic fibrosis and the incidence of hepatocellular carcinoma (HCC) associated with these therapies. METHODS: A total of 840 patients with CHB and concurrent hepatic fibrosis, who received antiviral therapy in Nanfang Hospital between June, 2010 and June, 2018, were enrolled in this follow-up cohort study. The patients were assigned to 3 cohorts matched for gender, age (difference≤5 years), HBeAg status and liver stiffness measurement (LSM) for treatment with one of the 3 antiviral drugs, namely entecavir, tenofovir dipivoxil and adefovir dipivoxil; each cohort was divided into 2 groups, with one of the groups having a combined treatment with Fufang Biejiaruangan tablet. The cumulative negative conversion rate of HBV DNA, normalization rate of ALT, hepatic fibrosis regression and the incidence of HCC were compared among the 3 cohorts and across the 6 groups at 144 weeks. RESULTS: A total of 749 patients were available to follow-up at 144 weeks. Compared with the baseline data, the cumulative negative conversion rate of HBV DNA increased gradually and the abnormal rate of ALT decreased significantly over time during the treatment in all the 6 groups (all < 0.001). Compared with the any of the antiviral drugs used alone, the combined treatments all resulted in significantly better antifibrotic effects (χ=11.345, χ=10.160, χ=6.358; all < 0.05). At 144 weeks, the incidence of HCC were 2.2%, 1.7%, 1.7% and 3.3% in enecavir group, enecavir with Biejiaruangan tablet group, adefovir group, and adefovir with Biejiaruangan tablet group, respectively, showing no significant difference between the two cohorts (4 groups; χ=6.813, =0.138). None of the patients in the 2 groups with tenofovir treatment had HCC by the end of the observation. CONCLUSIONS Antiviral therapy combined with antifibrotic therapy can effectively reverse hepatic fibrosis and reduce the incidence of HCC in patients with CHB; among the 3 antiviral drugs, tenofovir dipivoxil can be a better option for reducing the incidence of HCC in these patients.
Antiviral Agents ; Carcinoma, Hepatocellular ; etiology ; DNA, Viral ; Follow-Up Studies ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; complications ; Liver Neoplasms ; etiology ; Prospective Studies