Biparatopic anti-PCSK9 antibody enhances the LDL-uptake in HepG2 cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

Heterogeneity of fibroblast activation protein expression in the microenvironment of an intracranial tumor cohort: head-to-head comparison of gallium-68 FAP inhibitor-04 (68Ga-FAPi-04) and fluoride-18 fluoroethyl-L-tyrosine (18F-FET) in positron emission tomography-computed tomography imaging.

Background: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) can interact with tumor parenchymal cells to promote tumor growth and migration. Fibroblast activation protein (FAP) expressed by CAFs can be targeted with positron emission tomography (PET) tracers, but studies on FAP expression patterns in intracranial tumors remain scarce. We aimed to evaluate FAP expression patterns in intracranial tumors with gallium-68 FAP inhibitor-04 (68Ga-FAPi-04) and immunohistochemical staining and to observe the interactions between CAFs and tumor cells with a head-to-head comparison of 68Ga-FAPi-04 and fluoride-18 fluoroethyl-L-tyrosine (18F-FET) for PET quantification analysis. Methods: We prospectively enrolled 22 adult patients with intracranial mass lesions. 68Ga-FAPi-04 and 18F-FET PET-computed tomography (PET/CT) brain imaging were applied before surgery. Maximal tumor-to-brain ratio (TBRmax), metabolic tumor volume (MTV), and total lesion tracer uptake (TLU) was obtained, and different thresholds were used for 68Ga-FAPi-04-positive lesion delineation owing to the lack of relevant guidelines. The MTV and TLU ratios of both tracers were calculated. Linear regression was applied to observe the differential efficacy of semiquantitative PET parameters. Results: A total of 22 patients with a mean age of 50±13 years (range, 27-69 years) were enrolled. Heterogeneous patterns of 68Ga-FAPi-04 uptake [median of maximal standardized uptake value (SUVmax) =3.8; range, 0.1-19.1] were found. More malignant tumors, including brain metastasis, glioblastoma, and medulloblastoma, generally exhibited more significant 68Ga-FAPi-04 uptake than did the less malignant tumors, while the SUVmax and TBRmax exhibited nonsignificant differences across three intracranial lesion groups of primary brain tumor, brain metastasis, and noncancerous disease (SUVmax: P=0.092; TBRmax: P=0.189). Immunohistochemistry staining showed different stromal FAP expression status in various intracranial lesions. In 15 patients with positive 68Ga-FAPi-04 intracranial tumor uptake, the MTVFAPi:MTVFET ratio had differential efficacy in various types of intracranial tumors [95% confidence interval (CI): 0.572-7.712; P=0.027], and further quantification analyses confirmed the differential ability of the MTVFAPi:MTVFET ratio (95% CI: -0.045 to 11.013, P=0.052; 95% CI: 0.044-17.903, P=0.049; 95% CI: -1.131 to 30.596, P=0.065) with different isocontour volumetric thresholds. Conclusions: This head-to-head study demonstrated heterogeneous FAP expression in intracranial tumors. The FAP expression volume percentage in tumor parenchyma may therefore offer benefit with respect to differentiating between intracranial tumor types.

Prognostic Factors for Recurrent Glioma: A Population-Based Analysis.

Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616-0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS (P < .001). Conclusion: WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment.

Effect of Preheating and Post-Heating on the Microstructures and Mechanical Properties of TC17-Ti2AlNb Joint with Electron Beam Welding.

To enhance welding quality and performance, preheating and post-heating are usually employed on high-temperature materials, concurrently with welding. This is a novel technique in vacuum chamber electron beam welding (EBW). TC17 and Ti2AlNb alloys are the hot topics in aero-engine parts, and the welding of dissimilar materials is also a broad prospect. To settle welding cracks of Ti2AlNb, EBW with preheating and post-heating was investigated on TC17 and Ti2AlNb dissimilar alloy, which improved the manufacturing technology on high-temperature materials. The dissimilar joint no longer had cracks after preheating, which exhibited excellent welding stability and metallurgical homogeneity, and preheating and annealing had an important effect on mechanical properties. The joint strength after 630 °C annealing is higher than that of TC17 alloy base metal (BM) and other annealing temperatures, reaching 1169 MPa at room temperature and 894 MPa at 450 °C tensile condition. The joint plasticity after 740 °C annealing is equivalent to TC17 BM. EBW with preheating improved the microstructure characteristics and enhanced the plasticity of Ti2AlNb alloy weld and dissimilar joint, which would contribute to the application of Ti2AlNb alloy and Ti2AlNb dissimilar parts.

Occupational exposure to silica and risk of gastrointestinal cancers: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Although silica is a proven lung carcinogen, there is no convincing evidence linking crystalline silica to gastrointestinal malignancies. METHODS: We detailedly searched studies on the link between gastrointestinal malignancies and occupational silica exposure. Studies published between 1987 and 2023 were found by searching PubMed, Scopus, Cochrane Library, and Web of Science databases. Further studies were included from reference searching. We conducted a meta-analysis of the incidence and mortality of gastrointestinal malignancies and occupational silica exposure. We computed pooled-risk estimates using random effects models. Egger's regression asymmetry test and a funnel plot were used to identify publication bias. Moreover, sensitivity analysis and subgroup analysis were out. RESULTS: We identified 40 research with individuals from 13 different countries. The results indicate that occupational silica exposure raises the risk of gastric and esophageal cancer incidence, with pooled standardized incidence ratio of 1.35 (95% CI 1.21-1.51, p < 0.001), 1.31 (95% CI 1.04-1.65, p = 0.023), respectively, but there was a lack of statistically significant relationship between standardized mortality ratio. In addition, we found that silica exposure did not increase the risk of colorectal and pancreatic cancers. Occupational silica exposure was found to increase the risk of liver cancer, with pooled SIR and SMR of 1.19 (95% CI 1.04-1.35, p = 0.009), 1.24 (95% CI 1.03-1.49, p = 0.026), respectively. CONCLUSIONS: We discovered a link between occupational silica exposure and gastrointestinal malignancies, with cancers of the liver, stomach, and esophagus being the most prevalent. Colorectal and pancreatic cancer were not linked to occupational silica exposure.

First molecular detection and genetic characterization of porcine circovirus 4 in the Gansu Province of China.

Since its initial discovery in the Hunan province of China, genomic DNA of porcine circovirus 4 (PCV4) has been detected in pigs across multiple provinces in China, as well as in South Korea. However, the prevalence of porcine circovirus type 4 in Gansu Province, China, remains unknown. To address this gap, we undertook an extensive study where we gathered 121 clinical samples displaying diverse clinical manifestations from pig farms in Gansu Province between 2022 and 2023. Employing a real-time fluorescence quantification method, we identified the presence of PCV4 genome. Out of the 121 clinical samples analyzed, 13 samples tested positive for PCV4, resulting in a positive rate of 10.74% (13/121). This finding confirms the presence of PCV4 in pig farms within Gansu Province, China. Furthermore, we successfully sequenced and analyzed the complete genomes of two distinct PCV4 strains, comparing them with 60 reference sequences archived in the GenBank database. The results revealed a high nucleotide homology (98.2-98.8%) between the strains obtained in this study and the PCV4 reference strains, indicating a relatively low evolutionary rate of the PCV4 genome. Phylogenetic analysis revealed that two strains in this study belong to PCV4a and PCV4c. As far as we know, this study marks the inaugural report on the molecular identification and genomic attributes of PCV4 in Gansu Province, China, offering valuable insights for devising preventive and control strategies against this emerging virus.

Between the center and periphery: Commodification, formalisation, and infrastructuralisation of grassroots innovation.

The question of whether China can become a creative nation has been a topic of much debate in academic circles. The Chinese government has expressed its belief that China can develop a unique form of creativity to move the country from the periphery to the center of the global creative ecosystem. This perspective has led to a series of state-led trials and experiments, including the adoption of cultural and creative industries, creative clusters and cities, and the recent maker movement. This paper utilizes the center-periphery theory to analyze the emergence, development, and evolution of China's maker movement, aiming to revisit the creativity issues in contemporary China. Based on three years of ethnographic research, the paper unpacks the maker movement at three interrelated levels: individual, organizational, and urban. Empirical data indicates that the transformation of China's maker movement is characterized by commodification, formalization, and infrastructuralization processes. The tension between growth and development, and stability and control has turned the once grassroots maker movement into a contested creative hybrid. This paper challenges the conventional view that China is resistant to change and incapable of creativity due to institutional and ideological influences. It demonstrates how an alternative mode of creativity can emerge outside global creative centers and proposes a new perspective on China's potential to become a creative nation.

Non-Faradaic optoelectrodes for safe electrical neuromodulation.

Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of photoelectron storage and significant charge injection. Here, we report that zinc porphyrin, commonly used in dye-sensitized solar cells, can be self-assembled into nanorods and then coated by TiO2. The J-aggregated zinc porphyrin array enables long-range exciton diffusion and allows for fast electron transfer into TiO2. The formation of TiO2(e-) attracts positive charges around the neuron membrane, contributing to the induction of action potentials. Far-field cranial irradiation of the motor cortex using a 670 nm laser or an 850 nm femtosecond laser can modulate local neuronal firing and trigger motor responses in the hind limb of mice. The pulsed photoelectrical stimulation of neurons in the subthalamic nucleus alleviates parkinsonian symptoms in mice, improving abnormal stepping and enhancing the activity of dopaminergic neurons. Our results suggest injectable nanoscopic optoelectrodes for optical neuromodulation with high efficiency and negligible side effects.

Targeted nanotheranostics for the treatment of epilepsy through in vivo hijacking of locally activated macrophages.

Epilepsy refers to a disabling neurological disorder featured by the long-term and unpredictable occurrence of seizures owing to abnormal excessive neuronal electrical activity and is closely linked to unresolved inflammation, oxidative stress, and hypoxia. The difficulty of accurate localization and targeted drug delivery to the lesion hinders the effective treatment of this disease. The locally activated inflammatory cells in the epileptogenic region offer a new opportunity for drug delivery to the lesion. In this work, CD163-positive macrophages in the epileptogenic region were first harnessed as Trojan horses after being hijacked by targeted albumin manganese dioxide nanoparticles, which effectively penetrated the brain endothelial barrier and delivered multifunctional nanomedicines to the epileptic foci. Hence, accumulative nanoparticles empowered the visualization of the epileptogenic lesion through microenvironment-responsive MR T1-weight imaging of manganese dioxide. Besides, these manganese-based nanomaterials played a pivotal role in shielding neurons from cell apoptosis mediated by oxidative stress and hypoxia. Taken together, the present study provides an up-to-date approach for integrated diagnosis and treatment of epilepsy and other hypoxia-associated inflammatory diseases. STATEMENT OF SIGNIFICANCE: The therapeutic effects of antiepileptic drugs (AEDs) are hindered by insufficient drug accumulation in the epileptic site. Herein, we report an efficient strategy to use locally activated macrophages as carriers to deliver multifunctional nanoparticles to the brain lesion. As MR-responsive T1 contrast agents, multifunctional BMC nanoparticles can be harnessed to accurately localize the epileptogenic region with high sensitivity and specificity. Meanwhile, catalytic nanoparticles BMC can synergistically scavenge ROS, generate O2 and regulate neuroinflammation for the protection of neurons in the brain.

Evaluation of gut microbiota composition to screening for potential biomarker in AFB1-exposed sheep.

Aflatoxin B1 (AFB1) is an inevitable contaminant in animal feed and agricultural products, which seriously threatens the health of animals. However, there is currently no better diagnostic tool available than depending on clinical symptoms, pathophysiology, biochemical indicators, etc. Here, we profiled the fecal microbiomes of sheep exposed to and not exposed to AFB1 to identify potential non-invasive biomarkers of AFB1 intoxication by 16S rRNA gene sequencing technology, while measuring serum biochemical indexes. The results showed that the sheep exposed to AFB1 had significantly higher levels of the liver function indicators ALT (alanine transaminase) and AST (aspartate aminotransferase), and their microbial profiles were different from those of the CON (Control) group. In detail, the relative abundance of seven phyla and three genera were overrepresented in the AFB1 group from top 10 relative abundance. Importantly, we found that Prevotella and Bifidobacterium were significantly different in the CON and AFB1 groups (p = 0.032 and p = 0.021, respectively) based on linear discriminant analysis effect size (LEfSe) and random forest analysis. Additionally, the area under curve (AUC) of ALT was 1 (95% CI 1.00-1.00; p < 0.001) and that of Bifidobacterium was 0.95 (95% CI 0.81-1.00; p = 0.0275), suggesting that Bifidobacterium correlated with ALT (r = 0.783, p < 0.01) may be a potential biomarker for AFB1 exposure in sheep.

Genome-Wide Scanning Loci and Differentially Expressed Gene Analysis Unveils the Molecular Mechanism of Chlorantraniliprole Resistance in Spodoptera frugiperda.

Chlorantraniliprole has been widely used to controlSpodoptera frugiperda, but it has led to the development of chlorantraniliprole resistance. Multiomics analysis of strains with two extreme traits helps to elucidate the complex mechanisms involved. Herein, following genome resequencing and application of the Euclidean distance algorithm, 550 genes within a 16.20-Mb-linked region were identified from chlorantraniliprole-resistant (Ch-R) and chlorantraniliprole-susceptible (Ch-Sus) strains. Using transcriptome sequencing, 2066 differentially expressed genes were identified between Ch-R and Ch-Sus strains. Through association analysis, three glutathione S-transferase family genes and four trehalose transporter genes were selected for functional verification. Notably, SfGSTD1 had the strongest binding ability with chlorantraniliprole and is responsible for chlorantraniliprole tolerance. The Ch-R strain also increased the intracellular trehalose content by upregulating the transcription of SfTret1, thereby contributing to chlorantraniliprole resistance. These findings provide a new perspective to reveal the mechanism of resistance of agricultural pests to insecticides.

Divergent Total Syntheses of Illicium Sesquiterpenes through Late-Stage Skeletal Reorganization.

We disclose unified, protecting-group-free, bioinspired divergent total syntheses of eight allo-cedrane and seco-prezizaane Illicium sesquiterpenes and formal syntheses of five anislactone sesquiterpenes. The efficiency of our approach derives from rapid access to the 15-carbon tricyclic carboxylic acid through cationic epoxide-ene cyclization and HAT oxygenation, transformation of this intermediate into three distinct tricyclic precursors via Lewis acid-mediated skeletal reorganizations, subsequent programmed oxidation level enhancement, and a biomimetic oxidation-initiated skeletal rearrangement cascade. Consequently, we created a synthetic correlation map of the three most prevalent Illicium sesquiterpene families.

Staged or simultaneous operations for ventriculoperitoneal shunt and cranioplasty: Evidence from a meta-analysis.

OBJECTIVE: To date, there is no consensus on the surgery strategies of cranioplasty (CP) and ventriculoperitoneal shunt (VPS) placement. This meta-analysis aimed to investigate the safety of staged and simultaneous operation in patients with comorbid cranial defects with hydrocephalus to inform future surgery protocols. METHODS: A meta-analysis of PubMed, Ovid, Web of Science, and Cochrane Library databases from the inception dates to February 8, 2023 adherent to PRISMA guidelines was conducted. The pooled analyses were conducted using RevMan 5.3 software. The outcomes included postoperative infection, reoperation, shunt obstruction, hematoma, and subdural effusion. RESULTS: Of the 956 studies initially retrieved, 10 articles encompassing 515 patients were included. Among the total patients, 193 (37.48%) and 322 (62.52%), respectively, underwent simultaneous and staged surgeries. The finding of pooled analysis indicated that staged surgery was associated with lower rate of subdural effusion (14% in the simultaneous groups vs. 5.4% in the staged groups; OR = 2.39, 95% CI: 1.04-5.49, p = 0.04). However, there were no significant differences in overall infection (OR = 1.92, 95% CI: 0.74-4.97, p = 0.18), central nervous system infection (OR = 1.50, 95% CI: 0.68-3.31, p = 0.31), cranioplasty infection (OR = 1.58, 95% CI: 0.50-5.00, p = 0.44), shunt infection (OR = 1.30, 95% CI: 0.38-4.52, p = 0.67), reoperation (OR = 1.51, 95% CI: 0.38-6.00, p = 0.55), shunt obstruction (OR = 0.73, 95% CI: 0.25-2.16, p = 0.57), epidural hematoma (OR = 2.20, 95% CI: 0.62-7.86, p = 0.22), subdural hematoma (OR = 1.20, 95% CI: 0.10-14.19, p = 0.88), and intracranial hematoma (OR = 1.31, 95% CI: 0.42-4.07, p = 0.64). Moreover, subgroup analysis failed to yield new insights. CONCLUSIONS: Staged surgery is associated with a lower rate of postoperative subdural effusion. However, from the evidence of sensitivity analysis, this result is not stable. Therefore, our conclusion should be viewed with caution, and neurosurgeons in practice should make individualized decisions based on each patient's condition and cerebrospinal fluid tap test.

Solution-Processed Hybrid Europium (II) Iodide Scintillator for Sensitive X-Ray Detection.

Lead halide perovskite nanocrystals have recently demonstrated great potential as x-ray scintillators, yet they still suffer toxicity issues, inferior light yield (LY) caused by severe self-absorption. Nontoxic bivalent europium ions (Eu2+) with intrinsically efficient and self-absorption-free d-f transition are a prospective replacement for the toxic Pb2+. Here, we demonstrated solution-processed organic-inorganic hybrid halide BA10EuI12 (BA denotes C4H9NH4+) single crystals for the first time. BA10EuI12 was crystallized in a monoclinic space group of P21/c, with photoactive sites of [EuI6]4- octahedra isolated by BA+ cations, which exhibited high photoluminescence quantum yield of 72.5% and large Stokes shift of 97 nm. These properties enable an appreciable LY value of 79.6% of LYSO (equivalent to ~27,000 photons per MeV) for BA10EuI12. Moreover, BA10EuI12 shows a short excited-state lifetime (151 ns) due to the parity-allowed d-f transition, which boosts the potential of BA10EuI12 for use in real-time dynamic imaging and computer tomography applications. In addition, BA10EuI12 demonstrates a decent linear scintillation response ranging from 9.21 µGyair s-1 to 145 µGyair s-1 and a detection limit as low as 5.83 nGyair s-1. The x-ray imaging measurement was performed using BA10EuI12 polystyrene (PS) composite film as a scintillation screen, which exhibited clear images of objects under x-ray irradiation. The spatial resolution was determined to be 8.95 lp mm-1 at modulation transfer function = 0.2 for BA10EuI12/PS composite scintillation screen. We anticipate that this work will stimulate the exploration of d-f transition lanthanide metal halides for sensitive x-ray scintillators.

Relationship between spinal imbalance and knee osteoarthritis by using full-body EOS.

BACKGROUND: Orthostatic state is maintained by harmonizing the spine, pelvis and lower extremities. In the past few decades, several studies have demonstrated the associations between spinal imbalance and generalized osteoarthritis. The compensatory mechanisms of pelvis translation and knee flexion, however, have not been fully assessed. METHODS: A total of 213 volunteers, over 40 years of age, were recruited. Radiological measurements were performed by EOS imaging system. Pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), global tilt (GT), hip-knee-angle (HKA), knee flexion angle (KFA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. On the basis of SRS-Schwab, the subjects were classified into decompensated group (PI-LL > 20°), compensated group(10° ≤ PI-LL ≤ 20°), and normal group (PI-LL < 10°). Differences in radiographic parameters among groups were evaluated. Data of Knee Society Score (KSS) and Oswestry Disability Index (ODI) score were collected via questionnaires. RESULTS: Decompensated group showed larger pelvic parameters (PT) and low extremity parameters (LDFA, MPTA, HKA and KFA) than normal group (P < 0.05). Pelvic parameter was larger in the compensated group (median = 31°) compared to the normal group (median = 17°) (P < 0.05). There was no difference in low extremity parameters between the compensated and normal groups. At the sagittal plane, the radiological parameters of spine were greater in subjects with patellofemoral joint pain (PFP) than without PFP (P = 0.058). Higher PI-LL values were observed in women (P < 0.05). CONCLUSIONS: A correlation between sagittal spinal imbalance and knee joint angles was recognized. The progression of knee and low back pain was associated with the severity of sagittal spinal imbalance. Pelvic retroversion was considered to be the probable compensatory mechanism.

[Application of TightRope system combined with Locking-Loop biplane anatomical reconstruction technique for acute acromioclavicular joint dislocation].

Objective: To investigate the effectiveness of TightRope system combined with Locking-Loop biplane anatomical reconstruction technique in the treatment of acute acromioclavicular joint dislocation. Methods: A clinical data of 28 patients with acute acromioclavicular joint dislocation who met the selection criteria and admitted between June 2018 and December 2021 was retrospectively analyzed. There were 18 males and 10 females, with an average age of 47.7 years (range, 22-72 years). The causes of injury included falling (13 cases) and traffic accidents (15 cases). The acromioclavicular joint dislocation was rated as Rockwood type Ⅲ in 7 cases, type Ⅳ in 16 cases, and type Ⅴ in 5 cases. The time from injury to operation was 4-13 days, with an average of 9.5 days. The acromioclavicular joint dislocation was reconstructed with TightRope system and high-strength wire by Locking-Loop methods during operation. The operation time and complications were recorded. Visual analogue scale (VAS) score, Constant-Murley score, and active range of motion of shoulder (forward flexion and upward lift, abduction and upward lift, and external rotation) were recorded before operation and at 12 months after operation to evaluate the functional recovery of shoulder. The loss of acromioclavicular joint reduction was assessed by comparing the coracoclavicular distance (CCD) based on the anteroposterior X-ray films at 3 days and 12 months after operation. Results: The operation time was 58-100 minutes (median, 85 minutes). All incisions healed by first intention. All patients were followed up 12 months. During follow-up, 2 patients developed shoulder adhesion, which recovered after rehabilitation exercise. At 12 months after operation, the VAS score was significantly lower, the Constant-Murley score was significantly higher, and the range of motion of the shoulder joint (forward flexion and upward lift, abduction and upward lift, and external rotation) significantly increased when compared with preoperative ones ( P<0.05). X-ray films showed that the CCD was 8.4 (7.3, 9.4) and 9.2 (8.1, 10.1) mm at 3 days and 12 months after operation, respectively, with a significant difference ( Z=-4.665, P<0.001). During follow-up, there was no complication such as infection, titanium plate entrapment, fracture, internal fixation failure, or redislocation. Conclusion: The treatment of acute acromioclavicular joint dislocation with TightRope system combined with Locking-Loop biplane anatomical reconstruction has the advantages of small incision, joint reduction under direct vision, high fixation strength, and low incidence of postoperative complications, which can effectively relieve the pain of patients' shoulder joint and facilitate the recovery of shoulder joint function.

First Molecular Detection and Genetic Analysis of a Novel Porcine Circovirus (Porcine Circovirus 4) in Dogs in the World.

A novel circovirus species was identified in farmed pigs and designated porcine circovirus 4 (PCV4); it has recently been proved to be pathogenic to piglets. However, little is known about its cross-species transmission, and there is no evidence of PCV4 in dogs. A total of 217 fecal samples were collected from diarrheal dogs in Henan Province, China, and tested for the presence of PCV4 using a real-time PCR assay. Among the 217 samples, the total positivity rate for PCV4 was 5.99% (13/217 samples), with rates of 7.44% and 4.17% in 2020 and 2021, respectively. PCV4 was detected in dogs in 6 of 10 cities, demonstrating that PCV4 could be detected in dogs in Henan Province, China. One PCV4 strain (HN-Dog) was sequenced in this study and shared high levels of identity (97.9% to 99.6%) with reference strains at the genome level. Phylogenetic analysis based on complete genome sequences of HN-Dog and 42 reference strains showed that the HN-Dog strain was closely related to 3 PCV4 reference strains (from pig, raccoon dog, and fox) but differed genetically from other viruses in the genus Circovirus. Three genotypes, i.e., PCV4a, PCV4b, and PCV4c, were confirmed by phylogenetic analysis of complete genome sequences of 42 PCV4 strains, and one amino acid variation in Rep protein (V239L) and three amino acid variations in Cap protein (N27S, R28G, and M212L) were considered conserved genotype-specific molecular markers. In conclusion, the present study is the first to report the discovery of the PCV4 genome in dogs, and the association between PCV4 infection and diarrhea warrants further study. IMPORTANCE This study is the first to report the presence of PCV4 in dogs worldwide, and the first complete genome sequence was obtained from a dog affected with diarrhea. Three genotypes of PCV4 strains (PCV4a, PCV4b, and PCV4c) were determined, as supported by specific amino acid markers (V239L for open reading frame 1 [ORF1] and N27S R28G and M212L for ORF2). These findings help us understand the current status of intestinal infections in pet dogs in Henan Province, China, and also prompted us to accelerate research on the pathogenesis, epidemiology, and cross-species transmission of PCV4.

Associations between fine particulate matter and colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer (CRC) is the second deadliest cancer worldwide. The impact of fine particulate matter (PM2.5) on many diseases is a global concern, yet its association with CRC is unclear. This study aimed to assess the effect of PM2.5 exposure on CRC. We searched PubMed, Web of Science, and Google Scholar databases for population-based articles published before September 2022, providing risk estimates with 95% confidence intervals (CI). Among 85,743 articles, we identified 10 eligible studies across multiple countries and regions in North America and Asia. We calculated the overall risk, incidence and mortality and performed subgroup analyses according to countries and regions. The results revealed an association between PM2.5 and increased risk of CRC (total risk, 1.19 [95% CI 1.12-1.28]; incidence, OR=1.18 [95% CI 1.09-1.28]; mortality, OR=1.21 [95% CI 1.09-1.35]). The elevated risks of CRC associated with PM2.5 were different across countries and regions, at 1.34 [95% CI 1.20-1.49], 1.00 [95% CI 1.00-1.00], 1.08 [95% CI 1.06-1.10], 1.18 [95% CI 1.07-1.29], 1.01 [95% CI 0.79-1.30], in the United States, China, Taiwan, Thailand, and Hong Kong, respectively. Incidence and mortality risks were higher in North America than those in Asia. In particular, the incidence and mortality were highest in the United States (1.61 [95% CI 1.38-1.89] and 1.29 [95% CI 1.17-1.42], respectively) than those in other countries. This study is the first comprehensive meta-analysis to find a strong association between PM2.5 exposure and increased CRC risk.

Prediction of in-hospital hypokalemia using machine learning and first hospitalization day records in patients with traumatic brain injury.

AIMS: Hypokalemia is a common complication following traumatic brain injury, which may complicate treatment and lead to unfavorable outcomes. Identifying patients at risk of hypokalemia on the first day of admission helps to implement prophylactic treatment, reduce complications, and improve prognosis. METHODS: This multicenter retrospective study was performed between January 2017 and December 2020 using the electronic medical records of patients admitted due to traumatic brain injury. A propensity score matching approach was adopted with a ratio of 1:1 to overcome overfitting and data imbalance during subgroup analyses. Five machine learning algorithms were applied to generate a best-performed prediction model for in-hospital hypokalemia. The internal fivefold cross-validation and external validation were performed to demonstrate the interpretability and generalizability. RESULTS: A total of 4445 TBI patients were recruited for analysis and model generation. Hypokalemia occurred in 46.55% of recruited patients and the incidences of mild, moderate, and severe hypokalemia were 32.06%, 12.69%, and 1.80%, respectively. Hypokalemia was associated with increased mortality, while severe hypokalemia cast greater impacts. The logistic regression algorithm had the best performance in predicting decreased serum potassium and moderate-to-severe hypokalemia, with an AUC of 0.73 ± 0.011 and 0.74 ± 0.019, respectively. The prediction model was further verified using two external datasets, including our previous published data and the open-assessed Medical Information Mart for Intensive Care database. Linearized calibration curves showed no statistical difference (p > 0.05) with perfect predictions. CONCLUSIONS: The occurrence of hypokalemia following traumatic brain injury can be predicted by first hospitalization day records and machine learning algorithms. The logistic regression algorithm showed an optimal predicting performance verified by both internal and external validation.

[Effectiveness of arthroscopic long head of biceps tendon transposition combined with Swivelock anchor double fixation for massive and irreparable rotator cuff tears].

Objective: To investigate the effectiveness of arthroscopic long head of biceps tendon (LHBT) transposition combined with Swivelock anchor double fixation in treatment of massive and irreparable rotator cuff tears. Methods: Between June 2019 and November 2021, 25 patients with massive and irreparable rotator cuff tears were treated by arthroscopic LHBT transposition combined with Swivelock anchor double fixation. There were 12 males and 13 females. The age ranged from 47 to 74 years (mean, 62.4 years). The disease duration ranged from 1 to 62 months (median, 7 months). The rotator cuff tears were classified as Hamada grade 2 in 25 cases and Goutallier grade 1 in 2 cases, grade 2 in 22 cases, and grade 3 in 1 case. Pre- and post-operative shoulder range of motion (ROM), visual analogue scale (VAS) score, University of California Los Angeles (UCLA) score, and Constant-Murley score were recorded. Postoperative complications were observed. The reconstructed tissue integrity was confirmed by MRI. Results: All operations were successfully completed. The operation time was 120-330 minutes (mean, 189.6 minutes). All incisions healed by first intention. All patients were followed up 10-36 months (mean, 22.0 months). At last follow-up, the ROM in forward flexion, abduction, and external rotation, VAS score, UCLA score, and Constant-Murley score were superior to those before operation, and the differences were significant ( P<0.05). According to UCLA scoring standard, shoulder joint function was rated as excellent in 5 cases, good in 18 cases, and poor in 2 cases, with an excellent and good rate of 92.0%. No other complications occurred except shoulder joint adhesion in 2 cases. At last follow-up, MRI examination showed no retear of rotator cuff, and LHBT was intact. Conclusion: For massive and irreparable rotator cuff tears, arthroscopic LHBT transposition combined with Swivelock anchor double fixation can increase the force of pressing the humeral head, effectively relieve the pain, improve the ROM of joints, maximize the recovery of shoulder function, and do not increase the number of anchor nails.