Hypoxic environment promotes angiogenesis and bone bridge formation by activating Notch/RBPJ signaling pathway in HUVECs.

After epiphyseal fracture, the epiphyseal plate is prone to ischemia and hypoxia, leading to the formation of bone bridge and deformity. However, the exact mechanism controlling the bone bridge formation remains unclear. Notch/RBPJ signaling axis has been indicated to regulate angiogenesis and osteogenic differentiation. Our study aims to investigate the mechanism of bone bridge formation after epiphyseal plate injury, and to provide a theoretical basis for new therapeutic approaches to prevent the bone bridge formation. The expression of DLL4 and RBPJ was significantly up-regulated in HUVECs after ischemia and hypoxia treatment. Notch/RBPJ pathway positively regulated the osteogenic differentiation of BMSCs. HUVECs can induce osteogenic differentiation of BMSCs under ischemia and hypoxia. Notch/RBPJ pathway is involved in the regulation of the trans-epiphyseal bridge formation. Notch/RBPJ in HUVECs is associated with osteogenic differentiation of BMSCs and may participate in the regulation of the bone bridge formation across the epiphyseal plate.

A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility.

Disulfidptosis, a novel type of programmed cell death, has attracted researchers' attention worldwide. However, the role of disulfidptosis-related lncRNAs (DRLs) in liver hepatocellular carcinoma (LIHC) not yet been studied. We aimed to establish and validate a prognostic signature of DRLs and analyze tumor microenvironment (TME) and drug susceptibility in LIHC patients. RNA sequencing data, mutation data, and clinical data were obtained from the Cancer Genome Atlas Database (TCGA). Lasso algorithm and cox regression analysis were performed to identify a prognostic DRLs signature. Kaplan-Meier curves, principal component analysis (PCA), nomogram and calibration curve, function enrichment, TME, immune dysfunction and exclusion (TIDE), tumor mutation burden (TMB), and drug sensitivity analyses were analyzed. External datasets were used to validate the predictive value of DRLs. qRT-PCR was also used to validate the differential expression of the target lncRNAs in tissue samples and cell lines. We established a prognostic signature for the DRLs (MKLN1-AS and TMCC1-AS1) in LIHC. The signature could divide the LIHC patients into low- and high-risk groups, with the high-risk subgroup associated with a worse prognosis. We observed discrepancies in tumor-infiltrating immune cells, immune function, function enrichment, and TIDE between two risk groups. LIHC patients in the high-risk group were more sensitive to several chemotherapeutic drugs. External datasets, clinical tissue, and cell lines confirmed the expression of MKLN1-AS and TMCC1-AS1 were upregulated in LIHC and associated with a worse prognosis. The novel signature based on the two DRLs provide new insight into LIHC prognostic prediction, TME, and potential therapeutic strategies.

Percutaneous K-wire reduction and cast immobilization for severely displaced radial neck fractures in children.

The purpose of this study was to compare outcomes between percutaneous K-wire reduction cast immobilization (PKRC) and percutaneous K-wire reduction elastic intramedullary nailing combined with cast immobilization (PKRNC) for the treatment of radial neck fractures in children. This was a retrospective analysis of 62 radial neck fractures in children treated with PKRC or PKRNC. Thirty-one children were treated with percutaneous K-wire reduction, K-wire removal after reduction, and cast immobilization while 31 radial neck fractures in controls were managed using PKRNC. There were no significant differences between PKRC and PKRNC with regard to preoperative angulation ( P  = 0.556). The operation time in the PKRC group was significantly shorter than that of the PKRNC group ( P  = 0.023). There was no significant difference in the displacement angle when compared between the two groups on the first day and 1 month after surgery ( P  = 0.617, 0.72). The Mayo elbow performance score of the elbow joint function did not differ significantly between the two groups ( P  = 0.587). Although the hospital stay was not significantly different between groups (4.81 ±â€…1.07 vs. 4.16 ±â€…1.59 days; P  = 0.067), the PKRNC group required a second hospitalization to remove the elastic intramedullary nail 3 months after the operation. PKRC and PKRNC both achieved satisfactory outcomes for radial neck fractures in children. The operation time in the PKRC group was significantly lower than in the PKRNC group. PKRC does not require reoperation to remove internal fixation. Therefore, PKRC is recommended for radial neck fractures in children.

Preliminary fracture reduction in children with type III supracondylar humerus fractures during the COVID-19 pandemic.

During the COVID-19 pandemic, the time elapsed from injury to definitive surgery necessitated delay in type III pediatric supracondylar humerus fractures. Preliminary fracture reduction was recommended in these fractures while waiting for operative treatment. The purpose of this study was to evaluate whether preliminary reduction afforded a better treatment experience and improved outcomes. A retrospective cohort analysis of 161 type III supracondylar humerus fractures compared treatment with preliminary closed fracture reduction and delayed percutaneous pin placement (110 children) to delayed combined closed reduction and pin placement (51 children) in a children's medical center. Of the preliminary reduction group, 22 (20%) required analgesic pain relief, compared to 18 (35%) in the non-preliminary reduction group ( P  = 0.037), and the preliminary reduction group had statistically less pain (assessed using the Faces Pain Scale-Revised rating) the first night after injury and the first-night post-CRPP ( P  = 0.019, P  = 0.008). Cast splitting was more frequent in the non-preliminary reduction group, 11 patients (22%) than in the preliminary reduction group, 10 patients (9%; P  = 0.029). The operative times in the preliminary reduction group were shorter ( P  < 0.001). If delay is necessary for complete repair of type III supracondylar humerus fractures, a preliminary fracture reduction with a temporary cast can be recommended, as these children will experience a more comfortable interval, with less swelling and pain, and potentially a shorter operation. Level of Evidence: Level III-therapeutic study.

Relay Catalysis for Highly Selective Conversion of Methanol to Ethylene in Syngas.

The precise C-C coupling is a challenging goal in C1 chemistry. The conversion of methanol, a cheap and easily available C1 feedstock, into value-added and largely demanded olefins has been playing a game-changing role in the production of olefins. The current methanol-to-olefin (MTO) process, however, suffers from limited selectivity to a specific olefin. Here, we present a relay-catalysis route for the high-selective conversion of methanol to ethylene in syngas (H2/CO) typically used for methanol synthesis. A bifunctional catalyst composed of selectively dealuminated H-MOR zeolite and ZnO-TiO2, which implemented methanol carbonylation with CO to acetic acid and selective acetic acid hydrogenation to ethylene in tandem, offered ethylene selectivity of 85% at complete methanol conversion at 583 K. The selective removal of Brønsted acid sites in the 12-membered ring channel of H-MOR favors the selectivity of acetic acid in CH3OH carbonylation. The high capabilities of ZnO-TiO2 in the adsorption of acetic acid and the activation of H2 play key roles in selective hydrogenation of acetic acid to ethylene. Our work provides a promising relay-catalysis strategy for precise C-C coupling of C1 to C2 molecules.

Baseline Data and HLA Alleles and Haplotypes Diversity and Panel Reactive Antibody in Kidney Transplant Candidates in Southwest China.

BACKGROUND: To investigate the baseline data characteristic, human leukocyte antigen (HLA) polymorphisms, and panel reactive antibody (PRA) in end-stage kidney disease (ESKD) patients awaiting kidney transplantation in Southwest China. METHODS: HLA genotyping was performed using the real-time PCR sequence-specific primer. PRA was detected by enzyme-linked immunosorbent assay. The patients' medical records were extracted from the hospital information database. RESULTS: A total of 281 kidney transplant candidates with ESKD were analyzed. The average age was 35.7 ± 13.8 years. There were 61.6% patients had hypertension, 40.2% patients had dialysis ≥ 3 times per week, 47.3% patients had moderate or severe anemia, 30.2% patients with albumin < 35 g/L, 49.1% patients had serum ferritin < 200 ng/mL, 40.5% patients had serum calcium in target range (2.23 - 2.80 mmol/L), 43.4% patients had serum phosphate in target range (1.45 - 2.10 mmol/L), and 93.6% patients with parathyroid hormone > 88.00 pg/mL. In total, 15 HLA-A, 28 HLA-B, 15 HLA-DRB1, and 8 HLA-DQB1 allelic groups were identified. The most frequent alleles for each locus were HLA-A*02 (33.63%), HLA-B*46 (14.41%), HLA-DRB1*15 (21.89%), and HLA-DQB1*05 (39.50%). The most frequent haplotypes were HLA-A*33-B*58-DRB1*17-DQB1*02. A total of 9.60% of patients tested positive for PRAs - Class I or Class II. CONCLUSIONS: The data from this study provide some new insights into baseline data, the distribution of HLA polymorphisms, and PRA results in the population of Southwest China. This is of great significance in this region, and indeed in the country as a whole, in comparison with other populations and in the process of organ transplant allocation.

Antioxidants-related nuclear factor erythroid 2-related factor 2 gene variants associated with HBV-related liver disease.

BACKGROUND: Accumulating evidence demonstrated that nuclear factor erythroid 2-related factor 2 (NRF2) expression plays a crucial role in the proliferation, invasion and metastasis of hepatocellular carcinoma (HCC). However, research on the effect of NRF2 genetic polymorphism on the development of chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC) and HCC is still missing. METHODS: A total of 673 individuals were included in the study and classified into four groups: 110 CHB cases, 86 LC cases, 260 HCC cases, and 217 healthy controls. ​The polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing method were used to detect rs6721961 and rs6726395 polymorphisms. RESULTS: Patients carrying the T allele in rs6721961 were at a higher risk of HCC than individuals with the G allele compared to CHB patients (OR = 1.561, 95%CI: 1.003-2.430, P = 0.048). The statistically significant differences were also found in the rs6721961 GT genotype (OR = 2.298, 95% CI: 1.282-4.119, P = 0.005) and dominant model (OR = 2.039, 95% CI: 1.184-0.510, P = 0.010). Subgroup analysis also detected a significant association between the rs6721961 T allele and the development of HCC in older subjects (≥ 50 years) (OR = 2.148, 95% CI: 1.208-3.818, P = 0.009). Statistical analysis results indicated that subjects carrying haplotype G-A had a lower risk of HCC (OR = 0.700, 95% CI: 0.508-0.965, P = 0.028). CONCLUSIONS: For the first time, our findings provide evidence that the NRF2 gene rs6721961 variation is a potential genetic marker of susceptibility to HCC.

Efficacy of short-term splint immobilization in the treatment of pediatric discoid lateral meniscus after saucerization management.

There are no universal guidelines for rehabilitation after saucerization for children with discoid lateral meniscus. This study determined if short-term knee splint immobilization and delayed rehabilitation produces the same benefit as early rehabilitation after saucerization in children, in terms of knee function and pain intensity. A retrospective review was performed by categorizing patients into 2 groups depending on whether a splint immobilization was adopted postoperatively: for group A, rehabilitation began early without splint immobilization after surgery, and for group B, a knee splint was immobilized for 2 weeks. Numerical rating scale scores were collected in patients 1, 3, and 7 days, Lysholm scores were measured at 4 and 8 weeks postoperatively, and the gradual return to normal activities was documented. Forty-eight patients and 53 knees were included: group A had 30 patients with 31 knees, and group B had 18 patients with 22 knees. There was no improvement in numerical rating scale scores on the 1st (P=.519), 3rd (P=.421), and 7th (P=.295) postoperative days in group B. The Lysholm scores of group A (62.94 ±â€…8.68) was higher than that of group B (46.68 ±â€…9.82) measured 4 weeks following surgery, but there was no difference at 8 weeks (P=.237), and both groups had similar time to return to normal activities (P=.363). For discoid lateral meniscus patients who underwent isolated saucerization, short-term splint immobilization did not significantly help relieve postoperative pain. There was a comparable time-course for return to normal activities in both study groups.

Precisely Constructed Metal Sulfides with Localized Single-Atom Rhodium for Photocatalytic C-H Activation and Direct Methanol Coupling to Ethylene Glycol.

Although there are many studies on photocatalytic environmental remediation, hydrogen evolution, and chemical transformations, less success has been achieved for the synthesis of industrially important and largely demanded bulk chemicals using semiconductor photocatalysis, which holds great potential to drive unique chemical reactions that are difficult to implement by the conventional heterogeneous catalysis. The performance of semiconductors used for photochemical synthesis is, however, usually unsatisfactory due to limited efficiencies in light harvesting, charge-carrier separation, and surface reactions. The precise construction of heterogeneous photocatalysts to facilitate these processes is an attractive but challenging goal. Here, single-atom rhodium-doped metal sulfide nanorods composed of alternately stacked wurtzite/zinc-blende segments are successfully designed and fabricated, which demonstrate record-breaking efficiencies for visible light-driven preferential activation of C-H bond in methanol to form ethylene glycol (EG), a key bulk chemical used for the production of polyethylene terephthalate (PET) polymer. The wurtzite/zinc-blende heterojunctions lined regularly in one dimension accelerate the charge-carrier separation and migration. Single-atom rhodium selectively deposited onto the wurtzite segment with photogenerated holes accumulated facilitates methanol adsorption and C-H activation. The present work paves the way to harnessing photocatalysis for bulk chemical synthesis with structure-defined semiconductors.

The use of the ratio of C-reactive protein to albumin for the diagnosis of pediatric septic arthritis.

Purpose: This study aimed to investigate the relationship between the ratio of c-reactive protein to albumin (CAR) and pediatric septic arthritis (PSA). Methods: Clinical and laboratory data were collected. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of CAR in identifying PSA. Multivariable logistic regression analyses was performed to calculate adjusted odds ratio (OR) with 95% confidence interval (CI). Results: We included 305 patients with PSA (CAR ≤ 0.447, 182 patients; CAR > 0.447, 123 patients) between September 2013 and November 2022. ROC analysis showed that CAR performed best in diagnosing PSA, with an area under curve (AUC) value of 0.828. After adjusted for potential confounders, we found that high CAR was associated with PSA (OR = 6.85, 95% CI: 2.30-20.40, p = 0.001). In sensitivity analyses, subgroups analyses, and propensity score matching, the results remain stable. Conclusions: The CAR (>0.447) at admission was an independent risk factor for PSA. It is worthy to further investigate this association.

Salvianolic acid B inhibits RAW264.7 cell polarization towards the M1 phenotype by inhibiting NF-κB and Akt/mTOR pathway activation.

M1 macrophages secrete a large number of proinflammatory factors and promote the expansion of atherosclerotic plaques and processes. Salvianolic acid B (Sal B) exerts anti-inflammatory, antitumor and other effects, but no study has addressed whether Sal B can regulate the polarization of macrophages to exert these anti-atherosclerotic effects. Therefore, we investigated the inhibition of Sal B in M1 macrophage polarization and the underlying mechanism. The effects of different treatments on cell viability, gene expression and secretion of related proteins, phenotypic markers and cytokines were detected by MTT and western blot assays, RT‒qPCR and ELISAs. Cell viability was not significantly changed when the concentration of Sal B was less than 200 µM, and Lipopolysaccharide (LPS) (100 ng/mL) + interferon-γ (IFN-γ) (2.5 ng/mL) successfully induced M1 polarization. RT‒qPCR and ELISAs indicated that Sal B can downregulate M1 marker (Inducible Nitric Oxide Synthase (iNOS), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6)) and upregulate M2 marker (Arginase-1 (Arg-1) and Interleukin-10 (IL-10)) expression. Western blotting was performed to measure the expression of Nuclear Factor-κB (NF-κB), p-Akt, p-mTOR, LC3-II, Beclin-1, and p62, and the results suggested that Sal B inhibits the M1 polarization of RAW264.7 macrophages by promoting autophagy via the NF-κB signalling pathway. The study indicated that Sal B inhibits M1 macrophage polarization by inhibiting NF-κB signalling pathway activation and downregulating Akt/mTOR activation to promote autophagy.

Open Reduction of Displaced Radial Neck Fractures in Children by Internal Fixation Techniques: Comparison of Percutaneous Kirschner Wiring and Elastic Stable Intramedullary Nailing.

Background: Although most paediatric radial neck fractures can be treated with closed reduction, some severely displaced fractures require open reduction. The purpose of this study is to compare the effects of ESIN and KW fixation in open reduction of radial neck fracture in children. Methods: Twenty-four patients with mean age of 8.5 years were included. Four of the patients had a Judet type III fracture and 20 had a Judet type IV fracture. Ten patients who underwent percutaneous KW fixation were assigned to group A, while 14 patients who underwent ESIN fixation were assigned to group B. Variables of interest included age, sex, fracture type, associated lesions, surgical time, fracture reduction, cost, follow-up, healing time, X-rays, clinical outcomes, and complications. Results: There were no significant between-group differences in sex, age, additional injuries, fracture type, and quality of reduction. Costs were significantly lower in Group A. Fracture healing was achieved in 23 of 24 patients (10/10 in group A and 13/14 in group B). In a postoperative elbow function assessment based on the Steele and Graham classification, 80% of patients in group A had a score of excellent or good, compared to 78.6% of patients in group B. Two cases of nail shifting and joint protrusion were observed in group B, one of which also presented with nonunion during follow-up. Conclusions: Both KW and ESIN may achieve good clinical outcomes, but KW is associated with lower costs, easier implant removal (without the need for a secondary surgery), and lower iatrogenic complications.

Potential influence of factors for genu valgus with hereditary multiple exostoses.

Genu valgus is one of the most common limb deformities in hereditary multiple exostoses (HME). However, it is easily concealed and may account for subsequent osteoarthritis of the knee. The knees of 56 patients (33 men and 23 women) with HME were investigated bilaterally. Knee valgus was described by the mechanical axis deviation (MAD), mechanical lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA). We investigated sex, age, BMI, total number of palpable osteochondromas, number of radiographic osteochondromas around the knee, forearm deformities, morphology and distribution of lesions, and correlations between these factors and genu valgus. The measurement of LDFA and MPTA was performed to identify the sources of genu valgus deformity. Based on the measurement of the mechanical axis, limbs were classified as genu valgus (n = 22) or normal mechanical axis groups (n = 90). The different severities of the genu valgus patients were classified by MAD. By bivariate logistic regression, genu valgus was significantly associated with more sessile and flared metaphyseal lesions. However, only the number of flared metaphyseal lesions had a significant influence on the severity of genu valgus. By analyzing the LDFA and MPTA, it was found that abnormalities of both proximal tibia and distal femur play important roles in genu valgus. Early detection of sessile and flared metaphyseal knee lesions in patients with HME can contribute to early intervention of genu valgus. Level of relevance: Level 2.

Smart Nanomedicine to Enable Crossing Blood-Brain Barrier Delivery of Checkpoint Blockade Antibody for Immunotherapy of Glioma.

Immune checkpoint blockade (ICB) therapy has shown tremendous promises in the treatment of various types of tumors. However, ICB therapy with antibodies appears to be less effective for glioma, partly owing to the existence of the blood-brain barrier (BBB) that impedes the entrance of therapeutics including most proteins to the central nervous system (CNS). Herein, considering the widely existing nicotinic acetylcholine receptors (nAChRs) and choline transporters (ChTs) on the surface of BBB, a choline analogue 2-methacryloyloxyethyl phosphorylcholine (MPC) is employed to fabricate the BBB-crossing copolymer via free-radical polymerization, followed by conjugation with antiprogrammed death-ligand 1 (anti-PD-L1) via a pH-sensitive traceless linker. The obtained nanoparticles exhibit significantly improved BBB-crossing capability owing to the receptor-mediated transportation after intravenous injection in an orthotopic glioma tumor model. Within the acidic glioma microenvironment, anti-PD-L1 would be released from such pH-responsive nanoparticles, further triggering highly effective ICB therapy of glioma to significantly prolong animal survival. This work thus realizes glioma microenvironment responsive BBB-crossing delivery of ICB antibodies, promising for the next generation immunotherapy of glioma.

Treatment Choice of Complete Distal Forearm Fractures in 8 to 14 Years Old Children.

BACKGROUND: New surgical techniques have challenged traditional guidelines for nonsurgical treatment in pediatric and adolescent distal forearm fractures. This study was performed to compare outcomes and costs between closed reduction with percutaneous pinning (CRPP) and closed reduction with casting in the treatment of complete distal forearm fractures in children 8 to 14 years old. METHODS: A retrospective cohort study was performed of 175 displaced distal forearm fractures treated with 2 different methods in the emergency department of a children's trauma center. One hundred and fourteen children were managed using CRPP. The remaining 61 were treated with closed reduction and casting. All patients had initial follow-up radiographs. The quality of reduction and the residual angulation in both the coronal and sagittal planes were recorded. Outcomes included the angulation after reduction, residual angulation at final follow-up, radiation exposure, total immobilization time, days absent from school, total costs, and postoperative complications. RESULTS: The postreduction sagittal plane angulation was significantly lower in the CRPP group (P=0.037). While residual deformity between the groups at the 6-month final follow-up was not significantly different in either the sagittal or coronal planes (P=0.486, 0.726), patients in the nonoperative group received greater radiation than those in the operative group (P<0.001). Patients in the nonoperative group missed fewer classes and sustained lower costs (P<0.001, <0.001). The mean immobilization time in each group was not significantly different (31.4±4.4 vs. 32.8±5.9 d; P=0.227). CONCLUSIONS: Although the postreduction quality was a little better and radiation exposure was less in the CRPP group, there was no difference between the 2 groups in angulation, total immobilization time, or complication rates after 6 months. The cost and time absent from school of patients in the nonoperative group was significantly lower than in the operative group. There is no clear advantage to CRPP treatment on outcomes. Therefore, closed reduction and casting is recommended in complete distal forearm fractures of children 8 to 14 years old. LEVEL OF EVIDENCE: Level III-therapeutic study.

Plasma Levels of Heat Shock Protein 90 Alpha Associated With Colorectal Cancer Development.

Aim: The role of plasma heat shock protein 90 alpha (HSP90α) in colorectal cancer patients remains unclear. This study aimed to evaluate the relationship between HSP90α and the occurrence and development of colorectal cancer through diagnosis and prognosis value. Methods: 635 colorectal cancer patients and 295 healthy controls were recruited. The HSP90α was measured by using the ELISA kit in all objects and the immune cells and common biomarkers as CEA, AFP, CA125, CA153 and CA199 were measured in all colorectal cancer patients. The relationship between plasma HSP90α with clinical features, common tumor markers and immune cells were also conducted. The survival analysis endpoint was progression-free survival (PFS). Results: The levels of plasma HSP90α were significantly higher in colorectal cancer patients compared to healthy controls [51.4 (ng/ml) vs. 43.7 (ng/ml), p < 0.001]. In additional, the levels of plasma HSP90α were associated with gender and disease progress as stage, lymphatic and distant metastasis. Furthermore, plasma HSP90α was closed correlation with CEA, CA125, CA199 and percentage of B cells. However, the initial expression level of plasma HSP90α failed to show a prognostic value for progression-free survival in colorectal cancer. Conclusion: The plasma Hsp90α was remarkable higher in colorectal cancer and correlated with common tumor biomarkers and immune cells. Plasma Hsp90α levels were associated with disease progress but a poor diagnosis performance and also failed to show a prognostic value in colorectal cancer.

Association between WNT-1-inducible signaling pathway protein-1 (WISP1) genetic polymorphisms and the risk of gastric cancer in Guangxi Chinese.

BACKGROUND: WNT1-inducible signaling pathway protein 1 (WISP1) is a member of the CCN protein family and a downstream target of ß-catenin. Aberrant WISP1 expression may be involved in carcinogenesis. To date, no studies have investigated the association between single-nucleotide polymorphisms (SNPs) of WISP1 and gastric cancer. Therefore, we conducted this study to explore their relationship. METHODS: Polymerase chain reaction-restriction fragment length polymorphism assay was used to analyze three SNPs of WISP1 in 204 gastric cancer patients and 227 controls. RESULTS: Overall, we could not identify a significant association between WISP1 SNPs and gastric cancer risk. However, the subgroup analysis demonstrated that the presence of the rs7843546 T allele was associated with a significantly decreased risk of gastric cancer in those of Han Chinese ethnicity (CT vs. CC: OR = 0.33, 95%CI 0.14-0.78; TT vs. CC: OR = 0.29, 95%CI 0.11-0.76; CT + TT vs. CC: OR = 0.32, 95%CI 0.14-0.74). In addition, patients with the rs7843546 TT genotype display a 0.34-fold lower risk of developing stage I/II gastric cancer than those with the CC genotype Furthermore, individuals ≥ 50 years old who carried the rs10956697 AC genotype had a significantly decreased risk of gastric cancer (OR = 0.58, 95%CI 0.35-0.98). Smokers with the rs10956697 AC and AC + AA genotypes exhibited a 0.28-fold lower and 0.32-fold lower risk of gastric cancer, respectively. CONCLUSIONS: The WISP1 SNPs rs7843546 and rs10956697 were, for the first time, found to reduce susceptibility to gastric cancer in various subgroups of Guangxi Chinese.

miR-143 is implicated in growth plate injury by targeting IHH in precartilaginous stem cells.

Precartilaginous stem cells (PCSCs) are able to initiate chondrocyte and bone development. The present study aimed to investigate the role of miR-143 and the underlying mechanisms involved in PCSC proliferation. In a rat growth plate injury model, tissue from the injury site was collected and the expression of miR-143 and its potential targets was determined. PCSCs were isolated from the rabbits' distal epiphyseal growth plate. Cell viability, DNA synthesis, and apoptosis were determined with MTT, BrdU, and flow cytometric analysis, respectively. Real time PCR and western blot were performed to detect the mRNA and protein expression of the indicated genes. Indian hedgehog (IHH) was identified as a target gene for miR-143 with luciferase reporter assay. Decreased expression of miR-143 and increased expression of IHH gene were observed in the growth plate after injury. miR-143 mimics decreased cell viability and DNA synthesis and promoted apoptosis of PCSCs. Conversely, siRNA-mediated inhibition of miR-143 led to increased growth and suppressed apoptosis of PCSCs. Transfection of miR-143 decreased luciferase activity of wild-type IHH but had no effect when the 3'-UTR of IHH was mutated. Furthermore, the effect of miR-143 overexpression was neutralized by overexpression of IHH. Our study showed that miR-143 is involved in growth plate behavior and regulates PCSC growth by targeting IHH, suggesting that miR-143 may serve as a novel target for PCSC-related diseases.

Open reduction and internal fixation for displaced Salter-Harris type II fractures of the distal tibia: a retrospective study of sixty-five cases in children.

BACKGROUND: The treatment for displaced Salter-Harris II (S-H II) distal tibia fractures remains controversial. The purpose of this study was to review S-H II distal tibia fractures and evaluate the rate of premature physeal closure (PPC) treated by open reduction and internal fixation (ORIF). METHODS: We reviewed the charts and radiographs of S-H II fractures of the distal tibia with displacement > 3 mm between 2012 and 2019 treated by ORIF. Patients were followed up for a minimum of 6 months. CT scans of injured side or contralateral ankle radiograph were obtained if there was any evidence of PPC. Any angular deformity or shortening of the involved leg was documented. Multivariable logistic regression was performed to identify risk factors for the occurrence of PPC. RESULTS: A total of 65 patients with a mean age of 11.8 years were included in this study. The mean initial displacement was 8.0 mm. All patients but one were treated within 7 days after injury and the mean interval was 3.7 days. Supination-external rotation injuries occurred in 50 patients, pronation-eversion external rotation in 13, and supination-plantar flexion in two. The residual gap was less than 1 mm in all patients following ORIF and all fractures healed within 4-6 weeks. Superficial skin infection developed in one patient. Ten patients complained of the cosmetic scar. The rate of PPC was 29.2% and two patients with PPC developed a varus deformity of the ankle. Patients with associated fibular fracture had 7 times greater odds of developing PPC. Age, gender, injured side, mechanism of injury, amount of initial displacement, interval from injury to surgery, or energy of injury did not significantly affect the rate of PPC. CONCLUSIONS: ORIF was an effective choice of treatment for S-H II distal tibia fractures with displacement > 3 mm to obtain a satisfactory reduction. PPC is a common complication following ORIF. The presence of concomitant fibula fracture was associated with PPC.

Identification of two novel mutations in three children with congenital factor VII deficiency.

Congenital factor VII deficiency (FVIID) is a rare F7 gene mutation causing bleeding disorder inherited in an autosomal recessive manner. In this study, we aimed to identify genetic defects and analyze their relationships with phenotype in three Chinese FVIID patients. The diagnosis of FVIID was made based on FVII coagulant activity (FVII:C) levels assessed through prothrombin time assay. Direct sequencing and protein modeling were performed to detect genetic mutations and the resulting protein expression. Patient 1, a 2-year-old girl, presented with mild bleeding and was found to have a FVII:C of 0.2% and a compound heterozygous F7 Cys389Gly/Cys115Arg mutation. Patient 2, a 7-year-old boy, consulted for moderate bleeding and was found to have a FVII:C of 0.8% and a compound heterozygous F7 Thr241Asn/Pro324Leu mutation. Patient 3, a 5-year-old boy who developed a mild bleeding after trauma was found to have a FVII:C of 1.8% and a compound heterozygous F7 Thr241Asn/ IVS5-2A>G mutation. We hereby report three congenital FVIID patients with FVII:C less than 2% and their respective F7 mutations, two of which (F7 Cys115Arg, Pro324Leu) are novel. The molecular model analysis of the two novel mutations F7 Cys115Arg and Pro324Leu respectively indicated impairment of the proper folding of epidermal growth factor 1 domain situated on F7 gene and impairment of the procoagulant function of FVII both leading to the congenital deficiency of FVII.