[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Knee osteoarthritis(KOA)is a chronic joint disease characterized by degeneration of articular cartilage and joint pain.Its pathogenesis is complex,involving cell death,inflammatory responses and the interaction of various signaling pathways.Apoptosis is activated by Caspase family proteins and DNA endonucleases,leading to cellular dysfunction and promoting the degeneration of articular cartilage.Pyroptosis is a form of programmed cell death triggered by inflammasome activation,involving the activation of nucleotide-binding oligomeric domain-like receptor protein 3 inflammasome,which leads to the release of pro-inflammatory cytokines such as interleukin(IL)-6,IL-1 β and tumor necrosis factor-α.This release intensifies local inf/lammation and accelerates the progression of the disease.Ferroptosis is driven by iron-catalyzed lipid peroxidation,which induces the rupture of chondrocyte cell membranes and the degradation of matrix,thereby promoting joint degeneration.In addition,autophagy plays a dual role in KOA:moderate autophagy supports chondrocyte repair,while excessive autophagy may promote joint destruction,cartilage matrix degradation and subchondral bone sclerosis.The PI3K/AKT,NF-κB,Wnt/β-catenin and Hedgehog signaling pathways can regulate the growth,differentiation,proliferation,migration and apoptosis of articular chondrocytes.Single-cell RNA sequencing technology has provided new insights into the cellular heterogeneity and molecular mechanisms in the pathogenesis of KOA.This review explores the mechanisms of cell death in KOA,with a focus on the roles of pro-inflammatory cytokines,signaling pathway,and single-cell RNA sequencing techniques in the occurrence and progression of KOA.

Knee osteoarthritis(KOA)is a chronic joint disease characterized by degeneration of articular cartilage and joint pain.Its pathogenesis is complex,involving cell death,inflammatory responses and the interaction of various signaling pathways.Apoptosis is activated by Caspase family proteins and DNA endonucleases,leading to cellular dysfunction and promoting the degeneration of articular cartilage.Pyroptosis is a form of programmed cell death triggered by inflammasome activation,involving the activation of nucleotide-binding oligomeric domain-like receptor protein 3 inflammasome,which leads to the release of pro-inflammatory cytokines such as interleukin(IL)-6,IL-1 β and tumor necrosis factor-α.This release intensifies local inf/lammation and accelerates the progression of the disease.Ferroptosis is driven by iron-catalyzed lipid peroxidation,which induces the rupture of chondrocyte cell membranes and the degradation of matrix,thereby promoting joint degeneration.In addition,autophagy plays a dual role in KOA:moderate autophagy supports chondrocyte repair,while excessive autophagy may promote joint destruction,cartilage matrix degradation and subchondral bone sclerosis.The PI3K/AKT,NF-κB,Wnt/β-catenin and Hedgehog signaling pathways can regulate the growth,differentiation,proliferation,migration and apoptosis of articular chondrocytes.Single-cell RNA sequencing technology has provided new insights into the cellular heterogeneity and molecular mechanisms in the pathogenesis of KOA.This review explores the mechanisms of cell death in KOA,with a focus on the roles of pro-inflammatory cytokines,signaling pathway,and single-cell RNA sequencing techniques in the occurrence and progression of KOA.

Objective:To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender.Methods:This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient ( ICC). Results:A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions:Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

Objective:This study aimed to assess left atrial function in adults across various age groups using 4-dimensional automated left atrial quantification(4D Auto LAQ)technology.The study also aimed to compare the differences in two-dimensional(2D)and four-dimensional(4D)strains of the left atrium among different age groups, with the goal of enhancing the clinical utility of 4D Auto LAQ.Methods:A total of 409 healthy volunteers were recruited for the research.Two-dimensional and four-dimensional images were obtained using a GE Vivid E95 ultrasound system with a 4Vc four-dimensional probe.The study examined variations in 2D and 4D ultrasound parameters across various age groups.Furthermore, the relationship between left atrial reservoir strain(LASr), Left atrial conduit strain(LAScd), left atrial contraction strain(LASct), and age was explored.Results:The study involved 409 volunteers, with 217 males and 192 females, who were categorized into three age groups: young(18-45 years, n=56), middle-aged(46-65 years, n=202), and elderly(>65 years, n=151).Conventional ultrasound measurements indicated changes in left atrial anterior-posterior diameter with age progression: (31.70±3.65)mm for the young group, (34.02±3.91)mm for the middle-aged group, and(35.2±4.37)mm for the elderly group( P<0.01).The 2D and 4D left atrial parameters across the age groups were as follows: LASr(2D)(%): 37.48±7.51, 30.95±8.23, 26.9±7.56( P<0.01); LA VImax(ml/m 2): 23.54±5.79, 26.33±7.6, 28.99±8.15( P<0.01); LASr(%): 31.2±17.07, 22.5±8.59, 19.49±7.47( P<0.01).Both 2D and 4D left atrial parameters exhibited significant associations with age.Specifically, the correlations between LASr(2D)(%), LAScd(2D)(%), LASr(%), LAScd(%), and age were -0.429, 0.580, -0.354, 0.298, respectively( P<0.01). Conclusions:The 4D Auto LAQ technology is efficient in assessing left atrial function across various age groups, with age playing a significant role in influencing left atrial parameters.When compared to other ultrasound parameters, both 2D and 4D left atrial strain parameters have the ability to detect differences at an early stage, making them suitable for the early screening, evaluation, and monitoring of age-related left atrial dysfunction, especially in the elderly population.

Objective:To explore the risk factors for atrial fibrillation(AF)in elderly Chinese patients with severe valvular heart disease(VHD).Methods:This was a cross-sectional study and consecutively enrolled 978 elderly patients with severe VHD diagnosed in 18 Class A tertiary hospitals across the country from September 2021 to March 2022, including 322(32.9%)patients with concurrent AF.Clinical and echocardiographic data were collected to analyze the risk factors for AF.Results:Among VHD patients, compared with the non-AF group, the AF group was older, had a higher female ratio, higher diastolic blood pressure, higher proportions with cerebrovascular disease and chronic kidney disease, lower serum low density lipoprotein cholesterol and higher serum creatinine, amino-terminal A-type natriuretion peptide and glycosylated hemoglobin.As for echocardiographic parameters, the left atrial diameter was larger, the left ventricular end-diastolic diameter, interventricular septum thickness, and left ventricular posterior wall thickness were smaller in the AF group than in the non-AF group.All of the differences were statistically significant(all P<0.05). The results of multivariate Logistic regression analysis showed that the left atrial anteroposterior diameter increased( OR=1.166, P<0.01), the left ventricular end-diastolic diameter decreased( OR=0.929, P<0.01), and advanced age( OR=1.051, P<0.05)was an independent risk factor for elderly VHD patients with concurrent AF. Conclusions:In elderly patients with severe VHD, advanced age, an increased left atrial anteroposterior diameter, and a decreased left ventricular end-diastolic diameter were independently associated with AF.Therefore, evaluation of cardiac structure and regular follow-up should be performed in elderly patients with severe VHD for early intervention to reduce the incidence of AF.

Objective:To discuss the safety and feasibility for the use of 3D uniportal VATS sleeve resection.Methods:Totally 32 patients with central lung cancer received 3D uniportal VATS sleeve resection(group A) from June 2017 to May 2020 at Shanghai Chest Hospital. Meanwhile, 63 patients received conventional VATS sleeve resection(group B). The clinicopathological and perioperative outcome data were retrospectively collected and analyzed.Results:The baseline clinicopathological characteristics between these two groups were statistically similar. Compared with group B, the mean operative time[(174.19±73.69)min vs.(212.46±50.02)min, P=0.004] and blood loss[(73.13±42.70)ml vs.(130.48±133.72)ml, P=0.020] of group A were decreased, harvested lymph node stations was increased(7.63±1.59 vs. 6.76±1.70, P=0.018). Lymph nodes dissected showed no statistical difference(1.31±1.58 vs 1.21±1.96, P=0.803). There was no intraoperative death in both groups. Inspiringly, group A possessed lower rate of conversion to thoracotomy(0 vs. 36.5%, P=0.000), shorter chest drainage durations[(4.88±1.15)days vs.(6.81±3.8)days, P=0.007]. Although there were no deaths during hospitalization in both groups, the incidence of postoperative complications in group A was significantly lower than that in group B(25.0% vs. 47.6%, P=0.046). It also presented more complicated operations including pulmonary artery plasty(25.0% vs. 6.3%, P=0.024) and carina plasty(12.5% vs. 1.6%, P=0.005) against group B. Conclusion:3D uniportal VATS was a safe and feasible technique for the surgical treatment of central lung cancer when conducting a thoracoscopic sleeve resection.

This study reported two women with extreme obesity who underwent metabolic surgery due to their mutations in leptin receptor (LEPR).Genomic DNA was extracted from the anticoagulant blood samples of the two patients and their parents.A panel of genes related to metabolic diseases or whole exon sequencing was screened and the results were confirmed by Sanger sequencing.This is the first time that these three mutations in LEPR were reported.Two patients complained insatiety and early-onset obesity since childhood at clinics.Patient 1 was a 39-year-old woman with height 150 cm,weight 130 kg,and BMI 57.8 kg/m2.Serum leptin level was 156.4 μg/L.A homozygous mutation of c.2317G＞T was found in exon 15 of LEPR gene in patient 1,which was descended from her father and mother respectively.Patient 2 was a 37-year-old woman with height 158 cm,weight 167 kg,and BMI 67 kg/m2.Serum leptin level was 193.4 μg/L.Genetic analysis showed compound heterozygous mutations of c.1482delT and c.1892C ＞ A.Her father showed heterozygous c.1482delT mutation,and her mother carried heterozygous c.1892C ＞ A mutation.Two patients all underwent metabolic surgery with body weight reduction of about 22 kg and 40 kg respectively after first six months.However,the follow-up studies showed that the body weight of patient 1 rebounded to pre-surgery level in two years and patient 2 did not further lose weight in the following six months.

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

Objective As the population ages,clinicians are increasingly confronted with octogenarians with early-staged non-small cell lung cancer(NSCLC).We reviewed the outcomes of octogenarians who underwent lobectomy for clinical stagc Ⅰ NSCLC,to determine whether there was a benefit to the VATS approach in this group,and to analysis the risk factors of complication and survival.Methods We conducted a retrospective single-institution review of patients age 80 years or greater who underwent lobectomy for NSCLC from January 2006 to December 2016.Clinical outcomes including complication rate and survival rate were analyzed.Results 162 octogenarians underwent lobectomy:98 VATS and 64 through open thoracotomy.Compared with thoracotomy,VATS patients had fewer complications (14.3 ％ vs.28.1％,P =0.03),shorter length of tube duration [(3.5 ± 1.5) days vs.(4.9 ± 2.0) days,P =0.04],and shorter length of stay [(5.5 ± 2.1) days vs.(7.8 ± 3.5) days,P =0.04].For patients with pathologic stage Ⅰ disease,the 5-year overall survival was 64.5％,for stage Ⅱ was 38.1％,and for stage Ⅲ was 20.1％.The 5-year overall survival rates of pathological stage Ⅰ and stage Ⅱ,Ⅲ are of significant differences(P =0.001).In a multivariate logistic regression analysis,the approach of thoracotomy emerged as an independent predictor of complication (OR =1.94,95％ CI 1.214-5.135,P =0.03).In a multivariate COX regression analysis,pathological stage(OR =2.01,95％C1 1.453-5.865,P=0.03) and ASA(OR =1.81,95％CI 1.188-4.015,P =0.04) are independent predictors of over survival.Conclusion Octogenarians with NSCLC can undergo resection with low mortality and survival among stage Ⅰ patients,which is comparable with the general lung cancer population.The VATS approach reduces morbidity in this age demographic,resulting in shorter length of tube duration and shorter stay,while the approach of thoracotomy is an independent predictor of complication.Our study also demonstrated that pathological stage and ASA are independent predictors of overall survival rate.