Global incidence trends of autoimmune diseases from 1990 to 2021 and projections to 2050: A systemic analysis of the global burden of disease study 2021.

BACKGROUND: The analysis of the incidence trends of four autoimmune diseases (ADs) globally from 1990 to 2021, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), and psoriasis, reveals significant patterns of change, which further projects the incidence of these diseases at the global, regional, and national levels up to the year 2050. METHODS: The estimates for the number of incident cases and age-standardized incidence rates (ASIR), along with the 95 % uncertainty intervals (UI) for RA, IBD, MS and psoriasis, were obtained from the Global Burden of Diseases Study 2021. The estimated annual percentage change (EAPC) was used to quantify the global incidence trends of these four ADs from 1990 to 2021. Additionally, a Bayesian age-period-cohort model was employed to project the number of new cases and incidence rates of these four ADs up to 2050. RESULTS: From 1990 to 2021, the global ASIR of MS showed a declining trend (EAPC = -0.02 %, 95 % UI: -0.07 to 0.03), while the global ASIRs of IBD (EAPC = 0.29 %, 95 % UI: 0.20 to 0.38), RA (EAPC = 0.49 %, 95 % UI: 0.46 to 0.52), and psoriasis (EAPC = 0.23 %, 95 % UI: 0.21 to 0.26) demonstrated increasing trends. From 2022 to 2050, the global ASIRs of these four ADs are projected to rise, with the number of cases for all these conditions expected to continue increasing. CONCLUSIONS: The global incidence trends and projected changes in ADs reveal that the burden of ADs is expected to continue growing in the future, underscoring the necessity for developing targeted policies to address this emerging challenge.

Electroacupuncture ameliorates cardiac dysfunction in myocardial ischemia model rats: a potential role of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: To verify the hypothesis that electroacupuncture inhibits the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis regulating the expression of glial fibrillary acidic protein (GFAP) in the hippocampus of acute myocardial ischemia (AMI) rats. METHODS: Sixty-six healthy male Sprague-Dawley rats were randomly divided into five groups: Sham, AMI (Model), electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment (EA), non-acupoint electroacupuncture (Control), and Model + corticosterone (Model + CORT). AMI was induced occlusion of the left anterior descending coronary artery, followed by 3 d of electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment. In the Control group, electroacupuncture was applied at points lying 5 and 10 mm from the base of the tail. The AMI + CORT group was injected with CORT (20 mg/kg) in saline. Hemorheology, electrocardiography (ECG), hematoxylin and eosin staining, and expression of glycogen phosphorylase BB (GPBB) and heart-type fatty acid-binding protein (H-FABP) were used to assess cardiac function. The effects of adrenocorticotropic hormone (ACTH) and CORT were evaluated by enzyme-linked immunosorbent assay. Protein expression in the Sham and Model groups were screened by tandem mass tag-based quantitative proteomics analysis. Protein expression was evaluated by Western blotting (vimentin and GFAP) and immunofluorescence staining (GFAP). RESULTS: Compared with the Sham group, the hemorheology indicators, heart rate, ECG-ST segment elevation, and GPBB and H-FABP levels were higher in Model rats. The EA group showed reductions in these indicators compared with the Model group. Similarly, in Model rats, the expression of ACTH and CORT were significantly increased compared with the Sham group. The EA group also showed reduced expression of ACTH and CORT. Importantly, proteomics analysis showed that vimentin was differentially expressed in Model rats. Compared with the Sham group, vimentin and GFAP expression in the hippocampus was increased in the Model group but decreased in the AMI + EA group. Additionally, intraperitoneal injection of CORT aggravated the expression of GPBB, H-FABP and GFAP. CONCLUSIONS: Our results suggested that electroacupuncture may protect against cardiac injury induced by AMI through regulation of HPA axis hyperactivity, and that hippocampal GFAP may play an important role in the regulation.

Cancer-associated fibroblast infiltration in osteosarcoma: the discrepancy in subtypes pathways and immunosuppression.

Introduction: Osteosarcoma (OS), the primary malignant bone tumor, has a low survival rate for recurrent patients. Latest reports indicated that cancer-associated fibroblasts (CAFs) were the main component of tumor microenvironment, and would generate a variable role in the progression of tumors. However, the role of CAFs is still few known in osteosarcoma. Methods: The processed RNA-seq data and the corresponding clinical and molecular information were retrieved from the Cancer Genome Atlas Program (TCGA) database and processed data of tumor tissue was obtained from Gene Expression Omnibus (GEO) database. Xcell method was used in data processing, and Gene set variation analysis (GSVA) was used to calculates enrichment scores. Nomogram was constructed to evaluate prognostic power of the predictive model. And the construction of risk scores and assessment of prognostic predictive were based on the LASSO model. Results: This study classified Cancer Genome Atlas (TCGA) cohort into high and low CAFs infiltrate phenotype with different CAFs infiltration enrichment scores. Then TOP 9 genes were screened as prognostic signatures among 2,488 differentially expressed genes between the two groups. Key prognostic molecules were CGREF1, CORT and RHBDL2 and the risk score formula is: Risk-score = CGREF1*0.004 + CORT*0.004 + RHBDL2*0.002. The signatures were validated to be independent prognostic factors to predict tumor prognosis with single-factor COX and multi-factor COX regression analyses and Norton chart. The risk score expression of risk score model genes could predict the drug resistance, and significant differences could be found between the high and low scoring groups for 17-AAG, AZD6244, PD-0325901 and Sorafenib. Discussion: To sum up, this article validated the prediction role of CAF infiltration in the prognosis of OS, which might shed light on the treatment of OS.

Prediction model of colorectal cancer (CRC) lymph node metastasis based on intestinal bacteria.

BACKGROUND: Lymph node metastasis is the main metastatic mode of CRC. Lymph node metastasis affects patient prognosis. OBJECTIVE: To screen differential intestinal bacteria for CRC lymph node metastasis and construct a prediction model. METHODS: First, fecal samples of 119 CRC patients with lymph node metastasis and 110 CRC patients without lymph node metastasis were included for the detection of intestinal bacterial 16S rRNA. Then, bioinformatics analysis of the sequencing data was performed. Community structure and composition analysis, difference analysis, and intragroup and intergroup correlation analysis were conducted between the two groups. Finally, six machine learning models were used to construct a prediction model for CRC lymph node metastasis. RESULTS: The community richness and the community diversity at the genus level of the two groups were basically consistent. A total of 12 differential bacteria (Agathobacter, Catenibacterium, norank_f__Oscillospiraceae, Lachnospiraceae_FCS020_group, Lachnospiraceae_UCG-004, etc.) were screened at the genus level. Differential bacteria, such as Agathobacter, Catenibacterium, norank_f__Oscillospiraceae, and Lachnospiraceae_FCS020_group, were more associated with no lymph node metastasis in CRC. In the discovery set, the RF model had the highest prediction accuracy (AUC = 1.00, 98.89% correct, specificity = 55.21%, sensitivity = 55.95%). In the test set, SVM model had the highest prediction accuracy (AUC = 0.73, 72.92% correct, specificity = 69.23%, sensitivity = 88.89%). Lachnospiraceae_FCS020_group was the most important variable in the RF model. Lachnospiraceae_UCG - 004 was the most important variable in the SVM model. CONCLUSION: CRC lymph node metastasis is closely related to intestinal bacteria. The prediction model based on intestinal bacteria can provide a new evaluation method for CRC lymph node metastasis.

Astragaloside IV plays a role in reducing radiation-induced liver inflammation in mice by inhibiting thioredoxin-interacting protein/nod-like receptor protein 3 signaling pathway.

OBJECTIVE: To investigate the efficacy of Astragaloside IV (AS-IV) on radiation-induced liver inflammation in mice. METHODS: The mice were divided into normal group, dimethyl sulfoxide solvent group, irradiation group (IR), irradiation + AS-IV (20 mg/kg) group (IR+AS-20) and irradiation + AS-IV (40 mg/kg) group (IR+AS-40). One month after intraperitoneal injection of AS-IV, the mice were irradiated with 8Gry Co60γ, the blood was collected for biochemical analysis, and the liver was collected for hematoxylin-eosin staining, immunofluorescence and electron microscopic observation, oxidative stress, and Western blot analysis. RESULTS: The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate amino-transferase levels in serum induced by radiation; AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation; in addition, AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein (TXNIP) and nod-like receptor protein 3 (NLRP3) inflammasome in liver tissue after radiation; The expression of TXNIP, NLRP3 inflammasome, apoptosis-associated speck-like protein containing a CARD, cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group. CONCLUSIONS: These findings suggested that Co60γ radiation can cause structural and functional damage to the liver, which may be related to the NLRP3 mediated inflammatory pathway; AS-IV may play a protective role by inhibiting the TXNIP/NLRP3 inflammasome signaling pathway in the radiation-induced liver injury model.

Adsorption performance of GO-doped activated ATP composites towards tetracycline.

Antibiotic-related environmental contamination directly threatens ecosystems and human health. Adsorption is an efficient and simple treatment process for removing antibiotics from water environments. Attapulgite (ATP) is a natural clay mineral extensively researched as a promising adsorbent material in the food industry, pharmaceutical sanitation, and organic wastewater treatment. Graphene oxide (GO) is widely employed in the treatment of organic wastewater due to its superior physicochemical properties. Here, using high temperature and HCl, ATP was activated (a-ATP), and a GO/a-ATP composite was prepared via hydrothermal synthesis. Using an adsorbent dosage of 0.75 g L-1, pH = 5, reaction time of 120 min, initial temperature = 35 °C, and initial TC concentration of 50 mg L-1, the adsorption capacity of GO/a-ATP for TC was 38.8 mg g-1. The pseudo-first-order model (PFO) and pseudo-second-order (PSO) model were fitted to the kinetic data, and yielded an R 2-value of PSO (0.99991) > PFO (0.9389), indicating that the adsorption process is related to chemisorption. Adsorption was also well described by the mixed-order (MO) model (R 2 = 0.9827), demonstrating that two rate-limiting adsorption reaction steps, diffusion and adsorption, occur; the former exerting greater influence. Equilibrium data was fitted to Langmuir, Freundlich, and Temkin isotherm models; the Langmuir model gave the best fit, suggesting the adsorption process is a homogeneous and monolayer adsorption process. Various thermodynamic parameters such as standard Gibbs free energy (ΔG 0) and standard enthalpy (ΔH 0) were also calculated, these results indicate the adsorption reaction is an endothermic process. Our study shows that GO/a-ATP is a promising adsorbent material for use in the adsorption of tetracycline in aquatic environments.

Study on Intrinsic Influence Law of Specimen Size and Loading Speed on Charpy Impact Test.

Charpy impact energy/impact toughness is closely related to external factors such as specimen size. However, when the sample size is small, the linear conversion relationship between the Charpy impact energy of the sub-size and full-size Charpy specimens does not hold; the Charpy impact toughness varies with the size of the specimen and other factors. This indicates that studying the internal influence of external factors on impact energy or impact toughness is the key to accurately understanding and evaluating the toughness and brittleness of materials. In this paper, the effects of strain rate on the flow behavior and the effects of stress triaxiality on the fracture behavior of 30CrMnSiNi2A high-strength steel were investigated using quasi-static smooth bar and notched bar uniaxial tensile tests and Split Hopkinson Tensile Bar (SHTP). Based on the flow behavior and strain rate dependences of the yield behavior, a modified JC model was established to describe the flow behavior and strain rate behavior. Charpy impact tests were simulated using the modified JC model and JC failure model with the determined parameters. Reasonable agreements between the simulation and experimental results have been achieved, and the validity of the model was proved. According to the simulation results, the impact energy was divided into crack initiation energy, crack stability propagation energy and crack instability propagation energy. On this basis, the effects of striker velocity and specimen width on the energy and characteristic load of each part were studied. The results show that each part of the impact energy has a negligible dependence on the hammer velocity, but there is a significantly different positive linear relationship with the width of the sample. The energy increment of each part also showed an inverse correlation with the increase in the sample width. The findings reveal that the internal mechanism of Charpy impact toughness decreases with the increase in sample width; to a certain extent, it also reveals the internal reason why the linear transformation relationship of Charpy impact energy between sub-size specimens and standard specimens is not established when the specimens are small. The analytical method and results presented in this paper can provide a reference for the study of the dynamic behavior of high-strength steel, the relationship between material properties and sample size, and the elastic-plastic impact dynamic design.

Multimodal echocardiography in the diagnosis of masses localized to the proximal portions of pulmonary arteries.

Proximal pulmonary artery masses are exceedingly rare, and their diagnosis and therapy are important and challenging for clinicians. This study reviews our experience exploring the value of a combination of transthoracic echocardiography and contrast echocardiography for the differential diagnosis of proximal pulmonary artery masses. Between January 2018 and June 2021, 44 patients diagnosed with a mass attached to the major pulmonary artery and straddling the bilateral pulmonary arteries or pulmonary valve on transthoracic echocardiography were referred to this study. Contrast echocardiography was performed in 17 patients. Masses were diagnosed based on their site of attachment, shape, size, mobility, hemodynamic consequences on transthoracic echocardiography, and tissue perfusion on contrast echocardiographic perfusion imaging. Pathological data were collected from medical records and analyzed. The most frequent location of proximal pulmonary artery masses was the major pulmonary artery trunk. Twelve patients underwent complete mass resection, whereas nine patients underwent percutaneous pulmonary artery biopsy puncture and had a pathological diagnosis. Another 24 patients were confirmed with the validation methods. Contrast echocardiography has good sensitivity and specificity for differentiating thrombi from pulmonary artery sarcomas (PAS). The mass types were distributed as follows: thrombi (19, 43%), PAS (15, 34%), metastatic tumors (6, 14%), vegetations (3, 7%), and primary benign lesions (1, 2%). The majority of proximal pulmonary artery masses were thrombi or PAS. A combination of transthoracic echocardiography and contrast echocardiography offers advantages in the early identification of proximal pulmonary masses and provides clinically important information about the characteristics of masses, especially for differentiating thrombi from PAS.

High-Energy Phosphates and Ischemic Heart Disease: From Bench to Bedside.

The purpose of this review is to bridge the gap between clinical and basic research through providing a comprehensive and concise description of the cellular and molecular aspects of cardioprotective mechanisms and a critical evaluation of the clinical evidence of high-energy phosphates (HEPs) in ischemic heart disease (IHD). According to the well-documented physiological, pathophysiological and pharmacological properties of HEPs, exogenous creatine phosphate (CrP) may be considered as an ideal metabolic regulator. It plays cardioprotection roles from upstream to downstream of myocardial ischemia through multiple complex mechanisms, including but not limited to replenishment of cellular energy. Although exogenous CrP administration has not been shown to improve long-term survival, the beneficial effects on multiple secondary but important outcomes and short-term survival are concordant with its pathophysiological and pharmacological effects. There is urgent need for high-quality multicentre RCTs to confirm long-term survival improvement in the future.

The complete chloroplast genome of Schizostachyum dumetorum var. xinwuense (Bambusoideae: Poaceae).

Schizostachyum dumetorum var. xinwuense (T.H.Wen & J.Y.Chin) N.H.Xia is an arborescent bamboo that is native to Jiangxi, China. The bamboo culm wall of this species is extremely thin, which has high economic value and ecological benefits. Here, we assembled the complete chloroplast genome of S. dumetorum var. xinwuense using Illumina pair-end sequencing data in this work. The total genome size of S. dumetorum var. xinwuense was 139,230 bp in length, containing a large single-copy (LSC) region of 82,876 bp, a small single-copy (SSC) region of 12,877 bp, and a pair of inverted repeat (IR) regions of 21,777 bp. The overall GC content of the genome was 38.87%, and the corresponding GC values of the LSC, SSC, and IR regions were 36.98%, 32.83%, and 44.17%, respectively. The genome contained a total of 112 genes, including 75 protein-coding, 30 tRNA, and seven rRNA. Phylogenetic analysis of S. dumetorum var. xinwuense positioned it in a strongly supported clade with Arundinaria appalachiana. These data show the phylogenetic location of Schizostachyum dumetorum var. xinwuense within the family of the Bambusoideae and contribute to the biodiversity and systematics of the Bambusoideae.

The complete chloroplast genome of a solid type of Phyllostachys nidularia (Bambusoideae: Poaceae), a species endemic to China.

Phyllostachys nidularia (Bambusoideae: Poaceae), widely distributed in the Yangtze River Basin and various provinces (regions) in southern China, is one of the most important small and medium-sized bamboo species used in both bamboo shoots and timber. In the present study, we assembled a complete chloroplast genome of the economically important bamboo form Phyllostachys nidularia f. farcta H.R.Zhao & A.T.Liu using whole genome sequencing data previously reported. The complete chloroplast (cp) genome is 139,706 bp in length. A total of 129 unique genes were annotated, including 82 protein-coding, 39 tRNA, and eight rRNA genes. Phylogenetic analysis results supported that P. nidularia f. farcta was closely related to Phyllostachys reticulata. This work would help us better understand the evolution of the Phyllostachys cp genome.

A meta-analysis of Watson for Oncology in clinical application.

Using the method of meta-analysis to systematically evaluate the consistency of treatment schemes between Watson for Oncology (WFO) and Multidisciplinary Team (MDT), and to provide references for the practical application of artificial intelligence clinical decision-support system in cancer treatment. We systematically searched articles about the clinical applications of Watson for Oncology in the databases and conducted meta-analysis using RevMan 5.3 software. A total of 9 studies were identified, including 2463 patients. When the MDT is consistent with WFO at the 'Recommended' or the 'For consideration' level, the overall concordance rate is 81.52%. Among them, breast cancer was the highest and gastric cancer was the lowest. The concordance rate in stage I-III cancer is higher than that in stage IV, but the result of lung cancer is opposite (P < 0.05).Similar results were obtained when MDT was only consistent with WFO at the "recommended" level. Moreover, the consistency of estrogen and progesterone receptor negative breast cancer patients, colorectal cancer patients under 70 years old or ECOG 0, and small cell lung cancer patients is higher than that of estrogen and progesterone positive breast cancer patients, colorectal cancer patients over 70 years old or ECOG 1-2, and non-small cell lung cancer patients, with statistical significance (P < 0.05). Treatment recommendations made by WFO and MDT were highly concordant for cancer cases examined, but this system still needs further improvement. Owing to relatively small sample size of the included studies, more well-designed, and large sample size studies are still needed.

The complete chloroplast genome of Phyllostachys heteroclada f. solida (Poaceae).

Phyllostachys heteroclada f. solida is a precious wood-use bamboo resource, with almost solid stem. The complete chloroplast genome of the Phyllostachys heteroclada f. solida was the first time to assemble from Illumina pair-end sequencing data in this work. The total genome size of Phyllostachys heteroclada f. solida was 156,559 bp in length, containing a large single-copy (LSC) region of 89,200 bp, a small single-copy (SSC) region of 14,876 bp, and a pair of inverted repeat (IR) regions of 23,798 bp. The overall GC content of the genome was 36.12%, and the corresponding values of the LSC, SSC, and IR regions were 36.98, 33.15, and 44.22%, respectively. A total of 136 genes were annotated, including 88 protein-coding genes, 40 tRNA genes, and 8 rRNA genes. Phylogenetic analysis results strongly supported that Phyllostachys heteroclada f. solida was closely related to Phyllostachys reticulate.

Simultaneous transthoracic intervention for multiple cardiac defects in children.

BACKGROUND: Transthoracic intervention for isolated congenital heart disease (CHD) has been well tested for its technological feasibility and is increasingly used in clinical practice. We aimed to present our experience in simultaneous transthoracic intervention for multiple cardiac lesions in a series of pediatric patients. METHODS: Between March 2015 and December 2019, 20 patients with multiple CHD were referred to this study; mean age was 18.8±8.6 (range, 4-36) months. The transthoracic echocardiography (TTE) diagnosis was atrial septal defect (ASD) and perimembranous ventricular septal defect (pmVSD) in 7 patients, patent ductus arteriosus (PDA) and ASD in 6, pmVSD and PDA in 2, pmVSD and valvular pulmonary stenosis (PS) in 2, ASD and PS in 2, and doubly committed subarterial VSD (dcsVSD) and PS in 1 patient. These patients underwent simultaneous transthoracic interventions with transesophageal echocardiography guidance. The procedure sequence was PS→VSD→PDA→ASD. Electrocardiography and TTE were scheduled at discharge and follow-ups. RESULTS: All patients were occluded successfully without any thoracotomy conversion. Operation time was 56-120 (mean, 75±13) minutes. A 1.5-2.0-cm median sternum incision was performed in 6 ASD&PDAs, 2 ASD&PSs, and 1 dcsVSD&PS. In 11 other patients, a 1.5-2.0-cm incision in the inferior sternum was made and the chest closed with a drain. There were no serious complications before discharge and at follow-up. CONCLUSIONS: Simultaneous transthoracic intervention for multiple cardiac defects in children is feasible with good short-term outcomes. For different lesions, the appropriate surgical incision and operational sequence can render the intervention minimally invasive and safer.

Berberine augments hypertrophy of colonic patches in mice with intraperitoneal bacterial infection.

Colonic patches, the counterparts of Peyer's patches in the small intestine, are dynamically regulated lymphoid tissues in the colon that have an important role in defensing against microbial infections. Berberine is an isoquinoline alkaloid extracted from medicinal herbs including Rhizoma coptidis and has long been used for the treatment of infectious gastroenteritis, but its impact on the colonic lymphoid tissues (such as colonic patches) is unknown. In this study, we aimed to investigate whether berberine had any influences on the colonic patches in mice with bacterial infection. The results showed that oral berberine administration in bacterial infected mice substantially enhanced the hypertrophy of colonic patches, which usually possessed the features of two large B-cell follicles with a separate T-cell area. Moreover, the colonic patches displayed follicular dendritic cell networks within the B-cell follicles, indicative of mature colonic patches containing germinal centers. Concomitant with enlarged colonic patches, the cultured colon of infected mice treated with berberine secreted significantly higher levels of interleukin-1ß (IL-1ß), IL-6, TNF-α, and CCL-2, while NLRP3 inhibitor MMC950 or knockout of NLRP3 gene abrogated berberine-induced hypertrophy of colonic patches, suggesting the involvement of the NLRP3 signaling pathway in this process. Functionally, oral administration of berberine ameliorated liver inflammation and improved formed feces in the colon. Altogether, these results indicated that berberine was able to augment the hypertrophy of colonic patches in mice with bacterial infection probably through enhancing local inflammatory responses in the colon.

Plate Fixation versus Arthroscopic-Assisted Plate Fixation for Isolated Medium-Sized Fractures of the Greater Tuberosity: A Retrospective Study.

OBJECTIVES: To compare the clinical outcomes of plate fixation and arthroscopic-assisted plate fixation in patients with displaced isolated medium-sized fractures of the greater tuberosity. METHODS: From July 2013 to October 2017, patients with displaced isolated medium-sized fractures of the greater tuberosity who underwent arthroscopic-assisted plate fixation (ASPF group) or open reduction and internal plate fixation (ORIF group) were retrospectively reviewed and analyzed. There were 19 patients in the ASPF group and 27 patients in the ORIF group, with comparable demographic characteristics. The average age of patients was 49.4 ± 12.1 years in the ASPF group and 46.9 ± 11.4 years in the ORIF group. The shoulder function reflected by the Constant-Murley (CS) scores, the American Shoulder and Elbow Surgeons (ASES) scores, and the range of motion (ROM) in the both groups at the last follow-up were analyzed in the study. Surgery time, postoperative pain, and postoperative complications were also reviewed. RESULTS: A total of 46 eligible patients were included in this study. The mean follow-up was similar for the ASPF (19.4 ± 3.7 months) and the ORIF (18.2 ± 3.2 months) groups (P = 0.372). All patients had achieved primary incision healing in both groups at the last follow-up. The surgery time was 96.8 ± 11.7 min and 64.2 ± 8.3 min in the ASPF group and the ORIF group, respectively (P < 0.01). All the CS scores (P = 0.278), ASES scores (P = 0.426), and ROM were slightly better in the ASPF group than in the ORIF group, but they did not attain significant differences. In addition, there was no significant difference in the postoperative complication rate between the ASPF group (10.5%) and the ORIF group (18.5%) (P = 0.522). In the ASPF group, there was only one patient with postoperative shoulder stiffness and one case of fracture malunion. In the ORIF group, there were two cases of postoperative shoulder stiffness, two cases of fracture malunoin, and one case of subacromial impingement. Other major postoperative complications, such as fracture nonunion, pullout of the suture anchor, and screw penetration, were not observed in either group. CONCLUSION: Arthroscopic-assisted plate fixation is effective and may be an alternative in the treatment of displaced isolated medium-sized fractures of the greater tuberosity.

The Efficacy and Safety of Radiofrequency Catheter Ablation for Cardiac Arrhythmias in Pediatric Patients.

BACKGROUND: We aimed to evaluate the acute and long-term efficacy and safety of radiofrequency catheter ablation (RFCA) in Chinese pediatric patients with arrhythmias. METHODS: We gathered clinical data from pediatric patients who underwent RFCA in several large medical centers in China between 2000 and 2019. RESULTS: A total of 4,622 different substrates in 4,622 patients were ablated, with the majority consisting of supraventricular tachycardia (N = 3,831, 82.9%) and ventricular arrhythmias (VAs) (N = 791, 17.1%). The majority of supraventricular tachycardia (SVT) consists of atrioventricular reentry tachycardia (AVRT) (N = 2,492, 65.0%) and atrioventricular nodal reentry tachycardia (AVNRT) (N = 1,075, 28.1%). The accessory pathway location was left-sided in 1,237(49.7%) and right-sided in 1,251(50.3%) of the 2,488 pathways. The VAs consist of premature ventricular contraction (PVC) (N = 597, 75.5%) and ventricular tachycardia (VT) (N = 194, 24.5%). The duration of follow-up ranged from 1 month to 1 year. The overall acute/long-term success rate of RFCA was 96.4%/92.2%, AVRT 97.8%/93.5%, AVRT 99.3%/95.0, PVC 98.1%/92.2%, and VT 81.3%/75.2%. Serious complications occurred in 29 patients (0.6%). CONCLUSIONS: This present study shows that RFCA is effective and safe in the treatment of arrhythmias in Chinese pediatric patients, with a high success rate exceeding 90%, low recurrence rate, and significantly reduces the risk of complications. The success rate of left-sided pathway ablation is slightly higher than that of the right-sided pathway. There is no difference in the success rate of RFCA among children of different ages. It could be the first-line therapy in the majority of pediatric patients with SVT and/or VAs.

Molecular regulatory network of PD-1/PD-L1 in non-small cell lung cancer.

Lung cancer remains the most common cancer and the leading cause of cancer death worldwide. Despite effective chemotherapy and molecular-based therapies, the median and overall survival remains poor. Immune checkpoint inhibitors have changed the treatment landscape for patients with non-small cell lung cancer (NSCLC) by inhibiting negative T cell regulators, including programmed death 1 (PD-1, CD279) and programmed death ligand 1 (PD-L1, also known as B-H1, CD274) inhibitors. Nonetheless, most patients do not respond to these inhibitors. Recently, PD-L1 expression has been demonstrated to influence the anti-tumor efficacy of immune checkpoint inhibitors. However, the mechanisms of PD-L1 regulation are not clearly understood. This review thus aims to summarize the current knowledge and recent developments in the regulatory mechanisms of PD-L1 expression levels and attempts to clarify its latent function in anti-tumor activity, with the goal of guiding better designs for future NSCLC immunotherapies.

Caspase-3-mediated GSDME activation contributes to cisplatin- and doxorubicin-induced secondary necrosis in mouse macrophages.

OBJECTIVE: Induction of secondary necrosis/pyroptosis contributes to the toxicity of chemotherapeutic drugs, in which gasdermin E (GSDME) plays critical roles. This study aimed to explore whether GSDME is involved in mediating the cytotoxic effects of cisplatin and doxorubicin on mouse macrophages. METHODS: RAW 264.7 cells and bone marrow-derived macrophages (BMDMs) were treated with cisplatin or doxorubicin. Propidium iodide staining was used to assay necrosis, and immunoblotting was performed to detect protein expression. GSDME was knocked down by using small interfering RNA. Mice were injected intraperitoneally to evaluate toxicity to macrophages in vivo. Flow cytometry and immunofluorescence microscopy were adopted to analyse phenotypes of peritoneal cells. Cytokine levels were assayed by cytometric bead array. RESULTS: Both cisplatin and doxorubicin dose-dependently induced necrosis in mouse RAW 264.7 macrophages and BMDMs. Accompanying this, multiple caspases were activated, concomitant with the cleavage of poly (ADP-ribose) polymerase. Consistent with caspase-3 activation, GSDME was cleaved to generate its N-terminal fragment (GSDME-NT), thus leading to secondary necrosis/pyroptosis. Inhibition of caspase-3 significantly attenuated the generation of GSDME-NT concurrently with decreased necrosis in macrophages. GSDME knockdown also evidently decreased the necrosis in RAW 264.7 and BMDMs. Besides, cisplatin administration depleted peritoneal macrophages in mice, which was associated with caspase-3 activation and GSDME-NT generation. Consistent with the macrophage depletion, cisplatin administration significantly decreased survival of mice with bacterial infection. CONCLUSION: Chemotherapeutic cisplatin and doxorubicin exerted their cytotoxicity on macrophages partly by inducing caspase-3/GSDME-mediated secondary necrosis.