Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.

BACKGROUND:Arthroscopic single-row fixation with knotless suture bridge fixation techniques have been commonly used in the treatment of rotator cuff injuries,but the clinical efficacy in rotator cuff injuries combined with osteoporosis is unclear.OBJECTIVE:To investigate the clinical efficacy of arthroscopic single-row fixation versus knotless suture bridge fixation in the treatment of rotator cuff injuries combined with osteoporosis.METHODS:One hundred and twenty-two patients with rotator cuff injuries combined with osteoporosis who underwent arthroscopic treatment admitted to Affiliated Hospital of Xuzhou Medical University between January 2018 and August 2022 were retrospectively analyzed.They were divided into two groups according to the treatment plan.There were 63 patients with single-row fixation(single-row group)and 59 patients with knotless suture-bridge fixation(suture-bridge group).The visual analog scale scores for pain,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley score,and shoulder range of motion were compared between the two groups at the preoperative and 1 year postoperative periods.Rotator cuff re-tears were evaluated at 1 year postoperatively using the Sugaya staging criteria.The occurrence of complications was recorded in both groups.RESULTS AND CONCLUSION:(1)All patients received more than 1-year follow-up.No complications such as incision infection and nerve injury occurred in both groups after surgery.(2)Postoperative visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were significantly improved 1 year postoperatively in both groups compared with the preoperative period(P＜0.05).Visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were better in the suture-bridge group than in the single-row group 1 year postoperatively(P＜0.05).(3)At 1 year postoperatively,the re-tear rate in the single-row group[22％(14/63)]was significantly higher than that in the suture-bridge group[7％(4/59)],and the difference between the two groups was statistically significant(x2=5.777,P=0.016).(4)It is indicated that arthroscopic single-row fixation and knotless suture bridge fixation for rotator cuff injuries combined with osteoporosis both yielded satisfactory clinical outcomes,but knotless suture bridge fixation was more clinically effective,with a lower rate of postoperative retear.

BACKGROUND:Arthroscopic single-row fixation with knotless suture bridge fixation techniques have been commonly used in the treatment of rotator cuff injuries,but the clinical efficacy in rotator cuff injuries combined with osteoporosis is unclear.OBJECTIVE:To investigate the clinical efficacy of arthroscopic single-row fixation versus knotless suture bridge fixation in the treatment of rotator cuff injuries combined with osteoporosis.METHODS:One hundred and twenty-two patients with rotator cuff injuries combined with osteoporosis who underwent arthroscopic treatment admitted to Affiliated Hospital of Xuzhou Medical University between January 2018 and August 2022 were retrospectively analyzed.They were divided into two groups according to the treatment plan.There were 63 patients with single-row fixation(single-row group)and 59 patients with knotless suture-bridge fixation(suture-bridge group).The visual analog scale scores for pain,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley score,and shoulder range of motion were compared between the two groups at the preoperative and 1 year postoperative periods.Rotator cuff re-tears were evaluated at 1 year postoperatively using the Sugaya staging criteria.The occurrence of complications was recorded in both groups.RESULTS AND CONCLUSION:(1)All patients received more than 1-year follow-up.No complications such as incision infection and nerve injury occurred in both groups after surgery.(2)Postoperative visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were significantly improved 1 year postoperatively in both groups compared with the preoperative period(P＜0.05).Visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were better in the suture-bridge group than in the single-row group 1 year postoperatively(P＜0.05).(3)At 1 year postoperatively,the re-tear rate in the single-row group[22％(14/63)]was significantly higher than that in the suture-bridge group[7％(4/59)],and the difference between the two groups was statistically significant(x2=5.777,P=0.016).(4)It is indicated that arthroscopic single-row fixation and knotless suture bridge fixation for rotator cuff injuries combined with osteoporosis both yielded satisfactory clinical outcomes,but knotless suture bridge fixation was more clinically effective,with a lower rate of postoperative retear.

Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.

Objective:To investigate the effects of acetabular cup positions on the acetabular side stress in hip dysplasia after total hip arthroplasty (THA) using finite element analysis.Methods:Data were obtained from a 36-year-old female patient with developmental dysplasia of the hip. Three-dimensional finite element models were established for different acetabular cup positions using finite element analysis. Each model was categorized based on the center of rotation into four groups: anatomical rotation center, high rotation center, lateralized rotation center, superior-lateral rotation center. ANSYS software applied loads to the model to simulate the stress around the acetabulum in standing (588 N vertical stress) and walking conditions ( X=325 N, Y=-195 N, Z=1 462.5 N). Quantitative analyses of the relative displacement and stress at the acetabular-bone interface were conducted for each region under the two different loading conditions in all eight models. Results:In the standing position with a cup coverage of 90%, the relative displacement at the acetabular-bone interface was: 45.16 μm for the anatomical rotation center group, 47.57 μm for the high rotation center group, 77.27 μm for the lateralized rotation center group, and 96.13 μm for the superior-lateral rotation center group. Acetabular stress values were 9.07 MPa for the anatomical rotation center group, 11.23 MPa for the high rotation center group, 10.88 MPa for the lateralized rotation center group, and 17.75 MPa for the superior-lateral rotation center group. With a cup coverage of 70%, the relative displacements were 64.15, 65.71, 104.10, and 144.53 μm for the respective groups. The corresponding stresses were 9.30, 11.31, 13.98, and 21.45 MPa. In the walking state with a cup coverage of 90%, the relative displacements at the acetabular-bone interface were 189.67 μm for the anatomical rotation center group, 173.55 μm for the high rotation center group 311.03 μm for the lateralized rotation center group, and 572.93 μm for the superior-lateral rotation center group. The stresses were 39.92, 37.33, 47.92, and 71.94 MPa, respectively. With a cup coverage of 70%, the relative displacements were 239.09 μm for the anatomical rotation center group, 248.83 μm for the high rotation center group, 381.84 μm for the lateralized rotation center group, and 1105.90 μm for the superior-lateral rotation center group. The corresponding stresses were 40.62, 58.42, 56.26, and 3,606.30 MPa.Conclusion:With cup coverage at 70% and 90%, the high rotation center and anatomical rotation center exhibited lower and less frequent relative displacements at the acetabular-bone contact surface.

Objective:To discuss the perioperative management strategy of the HeartCon left ventricular assist device in the treatment of adult patients with end-stage heart failure and evaluate the effectiveness of blood pump.Methods:Ten consecutive patients with end-stage heart failure treated with the LVAD HeartCon at the Department of Cardiovascular Surgery, Jiangsu Province Hospital from July 2021 to July 2023 were enrolled in this study. The clinical data and follow-up results were retrospectively analyzed. Blood pump parameter, cardiac function classification, liver and kidney function, coagulation, myocardial markers, N-terminal pro-B-type natriuretic peptide, von Willebrand factor antigen, echocardiography, cardiothoracic ratio, and 6-minute walking distance test (6MWT) were evaluated before and after implantation of LVAD in 30, 60, 90, 180, 360, 540, and 720 days. EQ-5D-5L questionnaire was used to evaluate the quality of life.Results:There were 9 males and 1 female with a mean age of (53.7±9.7) years. All patients survived. Renal insufficiency occurred in 1 patient and recurrent aseptic granuloma occurred in 1 patient. There were no significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), serum creatinine (Scr), blood urea nitrogen (BUN), right ventricular fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) between pre-operation and 30, 60 and 90 days post-operation( P>0.05). The levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), von Willbrand factor (vWF) antigen, left ventricular end-diastolic diameter (LVDd) and cardiothoracic ratio decreased significantly on the 30th, 60th and 90th day after operation ( P<0.05). The left ventricular ejection fraction (LVEF), 6MWT and EQ-5D-5L scores were significantly increased at 30, 60 and 90 days after operation compared with those before operation ( P<0.05). Conclusion:With the left ventricular assist device HeartCon, the cardiac function and quality of life of patients were significantly improved within 3 months after operation, and no serious complications were observed, proving that the device is safe and effective.

To analyze the disease burden of Alzheimer′s disease (AD) in China from 1990 to 2021 and its trend of change, providing evidence for targeted interventions to reduce the burden of AD. A descriptive analysis of AD and its main risk factors among males and females of different ages in China from 1990 to 2021 was conducted using the Global Burden of Disease (GBD) 2021 database. The evaluation indicators were incidence rate, prevalence rate, mortality rate, and disability-adjusted life years (DALYs). The risk factors included high body mass index (BMI), high fasting plasma glucose, and smoking. The results showed that in 2021, the number of AD incidence among the Chinese population was 2 914 112 (204.8/100 000), the number of prevalence was 16 990 827 (1 194.2/100 000), the number of DALYs was 10 072 477 (708.0/100 000), and the number of deaths was 491 773 (34.6/100 000), which increased by 242.7%, 249.1%, 208.2%, and 239.4% respectively compared with 1990. In 2021, the AD incidence rate (264.4/100 000), prevalence rate (1 558.9/100 000), DALYs rate (935.8/100 000), and mortality rate (47.3/100 000) were all higher in women than in men. All rates showed a clear age-dependent trend. In 2021, the DALYs attributable to smoking, high BMI, and high fasting plasma glucose in the AD population in China were 602 501.1 (42.3/100 000), 466 728.7 (32.8/100 000), and 1 204 039.4 (84.6/100 000), respectively, with death tolls of 24 897.3 (1.7/100 000), 20 856.3 (1.5/100 000), and 58 838.2 (4.1/100 000). The proportion of DALYs attributable to high BMI showed an upward trend during 1990-2021, while the proportion of DALYs attributable to smoking showed a gradual decrease. The difference in the attributable risk factors between the genders was significant. In 2021, the highest risk among men was attributed to smoking, with DALYs rate and mortality rate of 68.3/100 000 and 2.7/100 000, respectively. In contrast, the highest risk among women was attributed to high fasting blood sugar, with DALYs rate and mortality rate of 111.1/100 000 and 5.6/100 000, respectively. In conclusion,the disease burden of AD is still increasing, and targeted interventions should be taken for both males and females to reduce the burden of AD by reducing unhealthy lifestyles.

Circular RNAs(CircRNAs)are a class of non-coding RNAs with a covalently closed-loop structure,high stability,and tissue specificity,with the production mechanisms different from linear RNAs.Recent studies have discovered that some CircRNAs can encode proteins via cap-independent translation mechanisms such as internal ribosome entry site,N6-methyladenosine,and rolling loop translation.The encoded proteins regulate homologous linear proteins or downstream signaling pathways via protein bait or other mecha-nisms,thereby exerting biological functions.Studies have shown that CircRNAs play a role in various diseases,especially in tumor progression,proliferation,invasion,and metastasis and immune regulation.Therefore,by elucidating the expression and roles of proteins encoded by CircRNAs in tumorigenesis and development,this pa-per is expected to provide new tumor markers and potential targets for tumor diagnosis and treatment.

Objective To explore the clinical significance of serum cytokine expression in the hepatitis B surface antigen(HBsAg)sero-clearance in patients with severe hepatitis B.Methods A nested case-control trial was conducted on 14 inpatients with severe hepatitis B admitted in our hospital from 2006 to 2020.Of them,7 patients(aged 36.57±3.15 years)achieved HBsAg sero-clearance within 1 year after the onset of hepatitis B flares(with abrupt rise of ALT level to＞5 times the upper limit of normal during HBV infection)and were assigned into HBsAg clearance group,while the other 7 patients(aged 34.14±2.97 years)only obtained HBsAg decreased less than 1 g within 1 year after the onset(HBsAg non-clearance group).Then,multiplex liquid-chip assay based on Luminex xMAP was used to detect the expression levels of 48 cytokines such as IFN-γ and IL-2 in serum samples of these 14 patients.Results The serum levels IFN-γ,IL-2Ra and SDF-1α were significantly lower in the HBsAg clearance group than the HBsAg non-clearance group(P＜0.05),but no statistical differences were observed in other 39 cytokines between the 2 groups.And there were 5 cytokines having no mutual expression in both groups.The copy number of HBV DNA was positively correlated with serum HGF(r=0.675,P=0.008)and SDF-1α levels(r=0.587,P=0.027),while negatively with IP-10(r=-0.600,P=0.023)and MIG level(r=-0.640,P=0.014).Meanwhile,a positive correlation was found between HBsAg titer and IL12-p70 level(r=0.593,P=0.025),and a negative correlation between HBsAg titer and TNF-α level(r=-0.609,P=0.021).In addition,the serum total bilirubin level was positively correlated with the expression of SCGF-β(r=0.543,P=0.045).Conclusion Three differentially expressed cytokines and some cytokines related to HBV DNA level and HBsAg titer are found,which may provide new insights into the underlying immunological mechanism of HBV virus clearance caused by hepatitis flares.Meanwhile,it also provides potential biomarkers for HBsAg serological clearance in patients with severe hepatitis B.

Objective:To explore the molecular mechanism of circDDX17 regulating the proliferation and apoptosis of non-small cell lung cancer cells by targeting the miR-223-3p/RIP3 molecular axis.Methods:The expression levels of circDDX17, miR-223-3p, and RIP3 in human normal lung epithelial cell lines BEAS-2B and non-small cell lung cancer cells H1299, A549, and H446 were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The plasmids of pcDNA, pcDNA-circDDX17, anti-miR-con, anti-miR-223-3p, pcDNA-circDDX17 and miR-con, pcDNA-circDDX17 and miR-223-3p mimics were transfected into H1299 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was used to detect the cell proliferation. Flow cytometry was used to detect the cell cycle and cell apoptosis. Plate cloning experiment was used to detect cell proliferation ability. The dual luciferase report experiment was applied to verify the targeting relationship between miR-223-3p with circDDX17 and RIP3. Western blot was used to detect the protein expression of cyclinD1, CDK2, cleaved caspase-3 and Bax.Results:The expression levels of circDDX17 and RIP3 mRNA in H1299, A549, and H446 cells were significantly reduced ( P<0.05), the expression level of miR-223-3p mRNA was significantly increased ( P<0.05) compared with BEAS-2B. The cell viability [(69.46±4.68)%], the number of cell clones (83.49±7.86), the proportion of cells in S phase [(22.52±1.41) %], the protein expression levels of cyclinD1 and CDK2 in PCDNa-CircDDX17 group were lower than those in pcDNA group [(97.54±7.72)%, 205.03±13.37, (28.69±1.49)%, respectively, P<0.05], while the percentage of G 0/G 1 phase cells [(64.45±3.56)%], apoptosis rate [(18.36±1.63)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17 group were higher than those of pcDNA group [(51.33±2.76) % and (5.21±0.54) %, respectively, P<0.05]. The viability [(72.64±5.44)%], the number of cell clones (78.16±8.23), the proportion of S-stage cells [(21.34±1.59) %], the protein expression levels of CyclinD1 and CDK2 in anti-miR-223-3p group were lower than those in anti-miR-con group [(103.47±6.25)%, 169.32±14.53, (28.43±1.26)%, respectively, P<0.05]. Percentage of G 0/G 1 phase cells [(62.86±3.28)%], apoptosis rate [(14.64±1.67)%], the protein expression levels of cleaved caspase-3 and Bax in the anti-miR-223-3p group were higher than those of anti-miR-con group [(51.33±2.71)% and (4.83±0.39)%, respectively, P<0.05]. MiR-223-3p has complementary sites with circDDX17 or RIP3. The viability [(135.45±9.28)%], the number of cell clones (174.64±10.68), the proportion of S-phase cells [(26.39±2.25)%], the protein expression levels of cyclinD1 and CDK2 in pcDNA-circDDX17+miR-223-3p group were higher than those in pcDNA-circDDX17+miR-con group [(101.56±6.68)%, 107.65±7.62, (21.64±1.72)%, P<0.05]. Percentage of G 0/G 1 phase cells [(56.64±2.76)%], apoptosis rate [(8.34±0.76)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17+miR-223-3p group were lower than those of pcDNA-circDDX17+miR-con group [(64.03±3.48)% and (15.21±1.18)%, respectively, P<0.05]. Conclusion:circDDX17 could inhibit the proliferation and induce apoptosis of non-small cell lung cancer cells via targeting the miR-223-3p / RIP3 molecular axis.