A prediction model for the risk of childhood allergic asthma was established through the analysis of public datasets. By using bioinformatics analysis methods, two datasets, GSE40732 and GSE40888, were selected, which included the whole-genome expression profile data of 222 children. Among them, GSE40732 was used as the training dataset to detect differentially expressed genes in peripheral blood mononuclear cells of children with the disease, and the master regulator analysis (MRA) algorithm was used to screen the master regulator genes in the inflammation-related pathway (GO: 0006954). After obtaining the master regulator genes, the expression of these master regulator genes in the GSE40732 and GSE40888 datasets was detected, and a prediction model was constructed through logistic regression, based on which risk scores were assigned to children. By comparing the risk scores of healthy children and children with the disease, the area under the curve (AUC) was used to evaluate the classification performance of the model. The average value of the risk scores of all children with the disease output by the model was calculated as the threshold. According to this threshold, the children with the disease in the two datasets were divided into high-risk and low-risk groups. The CIBERSORT algorithm was applied to analyze the infiltration of immune cells in the high-risk and low-risk groups, and the enrichment analysis of signaling pathways was completed using the msigdbr package in R software. The results showed that compared with healthy children, there were 377 up-regulated genes and 255 down-regulated genes in the peripheral blood mono-nuclear cells of children with the disease. The MRA algorithm analysis showed that there were five genes ( MUC5B, CST4, CCR7, TNF-α, and THBS1) that were the master regulator genes in the regulatory network. Risk score= MUC5B×3.47 +CST4×2.17 +CCR7×0.59 +TNF- α×0.54 +THBS1×1.67. The AUC in the GSE40732 and GSE40888 datasets were 0.874 and 0.682, respectively. Compared with the low-risk group, the resting memory CD4 +T cells and regulatory T cells in the peripheral blood of children with the disease in the high-risk group significantly decreased ( P<0.05), and both the IL-33 and IL-13 pathways were highly enriched. In conclusion, the model constructed in this study has a good predictive efficiency for the risk of allergic asthma and also has a certain effect on risk stratification.

A prediction model for the risk of childhood allergic asthma was established through the analysis of public datasets. By using bioinformatics analysis methods, two datasets, GSE40732 and GSE40888, were selected, which included the whole-genome expression profile data of 222 children. Among them, GSE40732 was used as the training dataset to detect differentially expressed genes in peripheral blood mononuclear cells of children with the disease, and the master regulator analysis (MRA) algorithm was used to screen the master regulator genes in the inflammation-related pathway (GO: 0006954). After obtaining the master regulator genes, the expression of these master regulator genes in the GSE40732 and GSE40888 datasets was detected, and a prediction model was constructed through logistic regression, based on which risk scores were assigned to children. By comparing the risk scores of healthy children and children with the disease, the area under the curve (AUC) was used to evaluate the classification performance of the model. The average value of the risk scores of all children with the disease output by the model was calculated as the threshold. According to this threshold, the children with the disease in the two datasets were divided into high-risk and low-risk groups. The CIBERSORT algorithm was applied to analyze the infiltration of immune cells in the high-risk and low-risk groups, and the enrichment analysis of signaling pathways was completed using the msigdbr package in R software. The results showed that compared with healthy children, there were 377 up-regulated genes and 255 down-regulated genes in the peripheral blood mono-nuclear cells of children with the disease. The MRA algorithm analysis showed that there were five genes ( MUC5B, CST4, CCR7, TNF-α, and THBS1) that were the master regulator genes in the regulatory network. Risk score= MUC5B×3.47 +CST4×2.17 +CCR7×0.59 +TNF- α×0.54 +THBS1×1.67. The AUC in the GSE40732 and GSE40888 datasets were 0.874 and 0.682, respectively. Compared with the low-risk group, the resting memory CD4 +T cells and regulatory T cells in the peripheral blood of children with the disease in the high-risk group significantly decreased ( P<0.05), and both the IL-33 and IL-13 pathways were highly enriched. In conclusion, the model constructed in this study has a good predictive efficiency for the risk of allergic asthma and also has a certain effect on risk stratification.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.

Objective:To compare proximal humerus internal locking system (PHILOS) and Multiloc intramedullary nail in the treatment of proximal humerus fracture-anterior dislocation.Methods:A retrospective study was performed to analyze the data of 33 patients with proximal humerus fracture-anterior dislocation who had been treated by open reduction and internal fixation from June 2015 to April 2021 at Department of Upper Limbs, Zhengzhou Orthopaedic Hospital. According to methods of internal fixation, the patients were divided into an extramedullary group and an intramedullary group. In the extramedullary group of 18 cases subjected to internal fixation with PHILOS, there were 8 males and 10 females with an age of (53.3 ± 10.6) years, and 1 2-part fracture, 15 3-part fractures and 2 4-part fractures by the Neer classification. In the intramedullary group of 15 cases subjected to internal fixation with Multiloc intramedullary nail, there were 8 males and 7 females with an age of (51.5 ± 11.2) years, and 14 3-part fractures and 1 4-part fracture by the Neer classification. The 2 groups were compared in terms of incision length, operation time, intraoperative blood loss, postoperative complications, and visual analog scale (VAS), range of shoulder motion, and Constant-Murley score at postoperative 12 months.Results:The 2 groups were comparable due to insignificant differences in their preoperative general data ( P>0.05). All patients were followed up for (20.8 ± 4.7) months. The incision length in the intramedullary group [(11.6 ± 1.7) cm] was significantly shorter than that in the extramedullary group [(17.6 ± 2.0) cm], and the intraoperative blood loss in the former [(106.7 ± 34.4) mL] was significantly lower than that in the latter [(151.7 ± 45.7) mL] ( P<0.05). The VAS scores at 1 week and 1 month after surgery [2.0 (2.0, 3.0) and 0.0 (0.0, 1.0) respectively] in the intramedullary group were significantly lower than those in the extramedullary group [3.0 (3.0, 3.3) and 1.0 (0.0, 1.3) respectively] ( P<0.05). The external rotation of the shoulder at the last follow-up in the intramedullary group (65.3° ± 15.5°) was significantly larger than that in the extramedullary group (50.6° ± 13.9°) ( P<0.05). There were no significant differences in operation time, incidence of postoperative complications, VAS score at 12 months after operation, Constant-Murley score or range of shoulder motion at the last follow-up between the 2 groups ( P>0.05). Conclusions:In the treatment of proximal humerus fracture-anterior dislocation, open reduction and internal fixation with both PHILOS and Multiloc intramedullary nail can result in a favorable prognosis when the fracture-dislocation is well reduced and fixated. However, the Multiloc intramedullary nail may lead to better early pain relief, less surgical invasion, and better functional recovery of the external rotation of the shoulder.

Objective:To evaluate the clinical efficacy of the axillary approach in the treatment of scapular glenoid fracture.Methods:A retrospective analysis was performed of the 12 patients who had been treated for scapular glenoid fracture from November 2019 to April 2021 at Department of Upper Limb Orthopaedics, Zhengzhou Orthopaedic Hospital. They were 4 males and 8 females, aged from 30 to 75 years (mean, 53.5 years). According to the Ideberg classification, there were 2 cases of type Ⅰa, 9 cases of type Ⅱ and one case of type Ⅴa. All cases were treated through the axillary approach. Two patients complicated with anterior shoulder dislocation were treated with manual reduction under anesthesia before operation and the other 10 cases with special plate fixation through the axillary approach. The 3 patients complicated with fracture of greater tuberosity were fixated with a special plate through the lateral shoulder split deltoid approach. Constant-Murley score, visual analogue scale (VAS) and Hawkins grading were used at the last follow-up to evaluate shoulder function, pain and stability after operation.Results:All patients were followed up for 9 to 20 months (mean, 14.4 months). The operation time ranged from 55 to 110 min (mean, 76.3 min), intraoperative bleeding from 60 to 160 mL (mean, 103.8 mL), and hospital stay from 8 to 14 d (mean, 11.1 d). All incisions healed primarily and all scapular glenoid fractures got united 6 months after operation. The last follow-up showed no shoulder instability, neurovascular injury or internal fixation failure. At the last follow-up, the range of motion of the shoulder was 159.2°±26.1° in forward bending, 156.7°±29.6° in abduction, 48.3°± 15.3° in external rotation (neutral position), and 73.3°±12.3° in internal rotation (neutral position), and the Constant-Murley score was (94.0±5.3) points. The range of motion of the shoulder and Constant-Murley score were significantly improved compared with those before operation (10.8°±11.6°, 7.5°±11.4°, 5.8°±10.0°, 42.5°±16.0° and 4.9±4.0, respectively) (all P<0.05). The VAS score was 0 in 11 patients and 2 in one patient at the last follow-up. Conclusion:The axillary approach is feasible for the treatment of scapular glenoid fracture, because it is hidden and less invasive, leading to good clinical outcomes.

BACKGROUND:Zinc-modified calcium silicate (CaSiO3) bioceramics coating on the titanium surface prepared in preliminary experiments has good chemical stability and antibacterial property. OBJECTIVE:To observe the effects of zinc-modified CaSiO3 bioceramics coating on osteointegration. METHODS:MC3T3-E1 cels were respectively cultured on the titanium with zinc-modified CaSiO3 bioceramics coating (experiment group), titanium with CaSiO3 bioceramics coating (control group) and pure titanium (blank control group). Then, cel adhesion, proliferation, calcification rate and the expression of type I colagen and osteocalcin were detected. The implant materials mentioned above were respectively inserted into the femurs of New Zealand white rabbits, and after 1.5 months, the osteoproliferation and osteointegration between the implants and the host were tested. RESULTS AND CONCLUSION:In vitro experiment: The number of adhesive cels at 12 hours after co-culture was significantly increased in the experimental group compared with the control group and blank control group (P < 0.05). At 14 days after co-culture, cel proliferation ability and ability of calcium nodule formation in the experiment group were significantly better than those in the other groups (P < 0.05). At 21 days after co-culture, there was no significant difference in the expression of type I colagen, but the expression of osteocalcin in the experiment group was higher than that in the control group and blank control group (P < 0.05).In vivo experiment: In the experiment group, a large amount of bone substances were detected, the coating materials directly contacted with the bone interface, new bone tissues and little fibrous tissues were observed at the interface. In contrast, there was a small amount of bone hyperplasia in the control group and almost no bone hyperplase in the blank control group. Moreover, a small part of the implant directly contacted with the bone interface and the most part was separated from bone trabeculae by fibrous tissues. These findings indicate that zinc-modified CaSiO3 bioceramics coating can enhance the ability of osteointegration between titanium implants and the host.