The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.

Objective:To evaluate the minimally invasive fixation with a locking plate via the tarsal sinus approach in the surgical treatment of Sanders Ⅱ and Ⅲ calcaneal fractures.Methods:A retrospective study was conducted to analyze the 65 patients who had been surgically treated for Sanders Ⅱ and Ⅲ calcaneal fractures at Department of Foot and Ankle Surgery, Binzhou Medical College Hospital from April, 2019 to September, 2020. There are 44 males and 21 females with an age of (42.5±10.4) years, and 46 Sanders type Ⅱ fractures and 19 Sanders type Ⅲ ones. The patients were divided into group L and group S according to surgical methods. Group S of 35 cases was fixated with a minimally invasive locking plate through the tarsal sinus incision while group L of 30 cases fixated with a locking plate through the L-shaped incision. The 2 groups were compared in terms of waiting time before surgery, surgical time, hospital stay, intraoperative bleeding, visual analogue scale (VAS) at 3 days after surgery, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score at 1 year after surgery, excellent and good rate by the Maryland foot function score, B?hler angle, Gissane angle, varus angle, and complications.Results:There was no significant difference in the general data before surgery between the 2 groups, showing comparability ( P>0.05). All patients were followed up for (13.3±1.6) months after surgery. The waiting time before surgery [(2.8±1.8) d], surgical time [(80.7±9.9) min], hospital stay [(6.7±1.9) d], intraoperative bleeding [(54.3±14.2) mL], and VAS at 3 days after surgery [6 (5, 7) points] in group S were all significantly less or lower than those in group L [(8.2±2.8) d, (105.0±15.7) min, (14.6±3.4) d, (74.3±12.8) mL, and 7 (6, 8) points] (all P<0.05). At one year after surgery, the AOFAS ankle-hindfoot score [(90.1±3.5) points] in group S was significantly higher than that in group L [(83.5±6.7) points] ( P<0.05), but there was no statistically significant difference in the excellent and good rate by the Maryland foot function score between the 2 groups [91.4% (32/35) versus 86.7% (26/30)] ( P=0.695). The B?hler angle, Gissane angle, and varus angle were significantly improved in all patients one year after surgery compared with the values before surgery ( P<0.05), but there were no statistically significant differences within either group or between the 2 groups at 3 days or 1 year after surgery ( P>0.05). Peroneal muscle pain was reported in 1 case in group S; there were 2 cases of skin necrosis, 1 case of incision hematoma and 1 case of sural nerve injury in group L. Conclusion:The minimally invasive fixation with a locking plate via the tarsal sinus approach is an effective treatment for Sanders Ⅱ and Ⅲ calcaneal fractures.

OBJECTIVE: To measure the concentration of bone morphogenetic protein 2 (BMP-2) in demineralized bone matrix (DBM) prepared from different long bones and to evaluate the osteoinductivity of different DBM on MC3T3-E1 cells. METHODS: Different bones from the same cadaver donor were used as the initial materials for making DBM, which were divided into ulna group (uDBM), humerus group (hDBM), tibia group (tDBM), and femur group (fDBM) according to the origins, and boiled DBM (cDBM) was taken as the control group. The proteins of DBM were extracted by guanidine hydrochloride, and the concentrations of BMP-2 were determined by ELISA assay. Then the DBM were co-cultured with MC3T3-E1 cells, the proliferation of MC3T3-E1 cells was observed by cell counting kit 8 (CCK-8) assay. The osteogenic differentiation ability of MC3T3-E1 cells was qualitatively observed by alizarin red, alkaline phosphatase (ALP), and Van Gieson staining, and the osteogenic differentiation ability of MC3T3-E1 cells was quantitatively analyzed by ALP content. Linear regression was used to analyze the effect of BMP-2 concentration in DBM on ALP synthesis. RESULTS: There were significant differences in the concentration of BMP-2 among the DBM groups (P<0.05). The concentrations of BMP-2 in the lower limb long bone were higher than those in the upper limb long bone, and the concentration of BMP-2 in the fDBM group was about 35.5 times that in the uDBM group. CCK-8 assay showed that the cells in each group continued to proliferate within 5 days of co-culture, and the absorbance (A) values at different time points were in the order of cDBM groupP<0.05). Linear regression analysis showed that y^=0.361+0.017x, the effect of BMP-2 concentration in DBM on cellular ALP content was significant (t=3.552, P=0.005); for every 1 ng/g increase in BMP-2 concentration, ALP content would increase by 0.017 [95%CI (0.006, 0.027)] U/100 mL. CONCLUSION The concentration of natural BMP-2 in different long bones varies greatly, and the lower limb long bone is higher than the upper limb long bone. The harvested location of bone material was an important factor affecting the osteoinductivity of DBM.
Alkaline Phosphatase ; Bone Matrix ; Bone Morphogenetic Protein 2 ; Cell Count ; Coloring Agents ; Osteogenesis ; Animals ; Mice

OBJECTIVE: To study the effectiveness of TightRope elastic fixation combined with functional total repair of the inferior tibiofibular ligament in the treatment of distal tibiofibular syndesmosis injury. METHODS: The clinical data of 34 patients with distal tibiofibular syndesmosis injury who met the selection criteria between January 2020 and January 2022 were retrospectively analyzed, and they were divided into improved group (TightRope elastic fixation combined with functional total repair of inferior tibiofibular ligament) and control group (distal tibiofibular screw fixation) according to the surgical methods, with 17 cases in each group. There was no significant difference in age, gender, body mass index, fracture type, and other baseline data between the two groups (P>0.05). The operation time, intraoperative blood loss, and complications were recorded in the two groups. The American Orthopaedic Foot and Ankle Society (AOFAS) score, ankle metatarsal flexion and dorsal extension range of motion were used to evaluate the ankle function. The patient satisfaction survey was conducted at last follow-up. RESULTS: All 34 patients were followed up 8-20 months, with a median of 13 months. The operation time and intraoperative blood loss in the improved group were significantly longer than that in the control group (P<0.05). In the improved group, no infection or poor reduction occurred, and only 1 patient had TightRope knot reaction at 6 months after operation. In the control group, there were 2 cases of poor reduction, 1 case of lower tibiofibular screw rupture, and 1 case of subcutaneous infection (cured after anti-infection treatment). There was no significant difference in the incidence of complications between the two groups (P>0.05). At last follow-up, the AOFAS score and ankle metatarsal flexion and dorsal extension range of motion of the improved group were significantly better than those of the control group (P<0.05). The satisfaction rates of patients in the improved group and the control group were 94.1% and 82.4%, respectively, showing significant difference (P<0.05). CONCLUSION TightRope elastic fixation combined with functional total repair of inferior tibiofibular ligament in the treatment of distal tibiofibular syndesmosis injury has sufficient fixation strength, and can achieve better effectiveness and joint function compared with traditional screw fixation.
Humans ; Ankle Joint/surgery* ; Blood Loss, Surgical ; Ligaments/surgery* ; Plastic Surgery Procedures ; Retrospective Studies ; Ankle Injuries/surgery*

OBJECTIVE: To compare the effectiveness of subtalar arthroereisis (STA) combined with modified Kidner procedure versus STA alone in the treatment of flexible flatfoot combined with painful accessory navicular bone in children. METHODS: The clinical data of 33 children with flexible flatfoot combined with painful accessory navicular bone who were admitted between August 2018 and August 2021 and met the selection criteria were retrospectively analyzed. They were divided into a combination group (17 cases, treated by STA combined with modified Kidner procedure) and a control group (16 cases, treated by STA alone) according to the surgical methods. There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, affected side of the foot, disease duration, and preoperative visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, talus-first metatarsal angle (T1MT), talus-second metatarsal angle (T2MT), talonavicular coverage angle (TCA), talus first plantar angle (Meary angle), calcaneal inclination angle (Pitch angle), and heel valgus angle (HV). The operation time, incision length, intraoperative blood loss, number of intraoperative fluoroscopies, and perioperative complications were recorded in both groups. The anteroposterior, lateral, and calcaneal axial X-ray films for the affected feet were taken regularly, and T1MT, T2MT, TCA, Meary angle, Pitch angle, and HV were measured. The VAS score, AOFAS ankle-hindfoot score were used to evaluate pain and functional recovery before and after operation. RESULTS: Surgeries in both groups were successfully performed without surgical complication such as vascular, nerve, or tendon injuries. Less operation time, shorter incision length, less intraoperative blood loss, and fewer intraoperative fluoroscopies were found in the control group than in the combination group ( P<0.05). One case in the combination group had partial necrosis of the skin at the edge of the incision, which healed after the dressing change and infrared light therapy, and the rest of the incisions healed by first intention. All children were followed up 12-36 months, with a mean of 19.6 months. At last follow-up, VAS score and AOFAS ankle-hindfoot score significantly improved in both groups when compared with preoperative ones ( P<0.05), and the differences of these scores between before and after operation improved more significantly in the combination group than in the control group ( P<0.05). Imaging results showed that the T1MT, T2MT, TCA, Meary angle, and HV significantly improved in both groups at last follow-up when compared with preoperative ones ( P<0.05), and the Pitch angle had no significant difference when compared with preoperative one ( P>0.05). But there was no significant difference in the difference of these indicators between before and after operation between the two groups ( P>0.05). CONCLUSION Both procedures are effective in the treatment of flexible flatfoot children with painful accessory navicular bone. STA has the advantage of minimally invasive, while STA combined with modified Kidner procedure has better effectiveness.
Humans ; Child ; Flatfoot/surgery* ; Blood Loss, Surgical ; Retrospective Studies ; Treatment Outcome ; Osteotomy/methods* ; Talus ; Pain

Objective:To compare the effect of temporal external fixator and digital guide plate in the immediate reconstruction of mandibular defect after segmental mandibulectomy.Methods:The clinical data of all patients who received segmental mandibulectomy and immediate mandibular reconstruction with free vascularized bone graft by a single surgical team in the Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from August 2016 to December 2017 were retrospectively analyzed. According to different auxiliary methods, the patients were divided into temporal external fixator (TEF) group and computer aided design-manufacture (CAD-CAM) group. The width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were measured by CT before and one month after surgery, and the difference before and after surgery was calculated to evaluate the surgical effect. SPSS 19.0 was used for statistical analysis, and the data were expressed as Mean ± SD. Independent sample t-test was used for comparison of indexes of surgical time and surgical effect evaluation between the two groups, and P<0.05 indicated statistically significant differences. Results:A total of 29 patients were enrolled, including 13 patients in TEF group, 4 males and 9 females, aged (47.7±14.5) years, including 7 ameloblastomas, 2 squamous cell carcinomas, 2 abnormal proliferation of bone fibers, 1 rhabdomyosarcoma and 1 osteosarcoma. In the CAD-CAM group, there were 16 cases, including 11 males and 5 females, aged (42.4±19.7) years, including 10 ameloblastomas, 3 squamous cell carcinomas, 1 osteoblastoma, 1 otogenic fibromyxoma and 1 osteosarcoma. The bone grafts in 29 patients were all alive, the wounds healed primarily, and the occlusal relationship and facial contour of the patients were fine. After 3 years follow-up, there were no postoperative complications and tumor recurrence. The function of the supply area was not affected. The operative time was (7.12±1.40) h in the TEF group and (4.72±1.10) h in the CAD-CAM group, and the difference between the two groups was statistically significant ( P<0.01). In the TEF group, the difference of the width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were (1.08±1.12) mm, (2.08±1.61) mm, (1.77±3.15) mm, respectively; CAD-CAM group were (0.88±1.15) mm, (0.94±1.34) mm, (0.87±1.47) mm, respectively, and there was no statistical significance between the two groups ( P>0.05). Conclusions:It took significantly longer to perform immediate mandibular reconstruction assisted by TEF than that assisted by CAD-CAM in surgery, but both groups achieved better surgical results. It is simpler and more effective to use TEF when time is urgent or technology is too limited to carry out preoperative digital design.

Objective:To compare the effect of temporal external fixator and digital guide plate in the immediate reconstruction of mandibular defect after segmental mandibulectomy.Methods:The clinical data of all patients who received segmental mandibulectomy and immediate mandibular reconstruction with free vascularized bone graft by a single surgical team in the Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from August 2016 to December 2017 were retrospectively analyzed. According to different auxiliary methods, the patients were divided into temporal external fixator (TEF) group and computer aided design-manufacture (CAD-CAM) group. The width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were measured by CT before and one month after surgery, and the difference before and after surgery was calculated to evaluate the surgical effect. SPSS 19.0 was used for statistical analysis, and the data were expressed as Mean ± SD. Independent sample t-test was used for comparison of indexes of surgical time and surgical effect evaluation between the two groups, and P<0.05 indicated statistically significant differences. Results:A total of 29 patients were enrolled, including 13 patients in TEF group, 4 males and 9 females, aged (47.7±14.5) years, including 7 ameloblastomas, 2 squamous cell carcinomas, 2 abnormal proliferation of bone fibers, 1 rhabdomyosarcoma and 1 osteosarcoma. In the CAD-CAM group, there were 16 cases, including 11 males and 5 females, aged (42.4±19.7) years, including 10 ameloblastomas, 3 squamous cell carcinomas, 1 osteoblastoma, 1 otogenic fibromyxoma and 1 osteosarcoma. The bone grafts in 29 patients were all alive, the wounds healed primarily, and the occlusal relationship and facial contour of the patients were fine. After 3 years follow-up, there were no postoperative complications and tumor recurrence. The function of the supply area was not affected. The operative time was (7.12±1.40) h in the TEF group and (4.72±1.10) h in the CAD-CAM group, and the difference between the two groups was statistically significant ( P<0.01). In the TEF group, the difference of the width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were (1.08±1.12) mm, (2.08±1.61) mm, (1.77±3.15) mm, respectively; CAD-CAM group were (0.88±1.15) mm, (0.94±1.34) mm, (0.87±1.47) mm, respectively, and there was no statistical significance between the two groups ( P>0.05). Conclusions:It took significantly longer to perform immediate mandibular reconstruction assisted by TEF than that assisted by CAD-CAM in surgery, but both groups achieved better surgical results. It is simpler and more effective to use TEF when time is urgent or technology is too limited to carry out preoperative digital design.

PLEK2 (Pleckstrin-2) is a subtype of platelets and leukocytes Pleckstrin, located at 14q23.3-q24.1. Its encoded protein contains 353 amino acids. It plays a role in a variety of cells other than immune cells. The research is relatively limited, mainly involved in the reorganization of cytoskeleton proteins and the regulation of cell extension and migration. PLEK2 plays an important role in the occurrence, development and metastasis of a variety of tumors, and can participate in the regulation of a variety of signal pathways, thereby regulating tumor cell proliferation, invasion and metastasis. PLEK2 is up-regulated in a variety of tumors and has carcinogenic properties. This article reviews the regulatory role of PLEK2 in tumorigenesis, development and metastasis and its impact on tumor prognosis.

Metal-organic frameworks (MOFs) are mixed porous materials which are composed of metal clusters or ions and organic pillars. Given their channel tunability, high porosity, large specific surface area, and good biocompatibility, MOFs can be combined with various biological macromolecules. In recent years, they have been widely studied in the field of biomedicine, especially in the loading of anti-tumor drugs, showing great application prospects. Multifunctional anti-tumor MOF combined with different therapeutic methods provides a new idea and method for tumor treatment. On the basis of the structure of MOF, this paper introduces the advantages of using MOF to load anti-tumor drugs and reviews the application of MOF in tumor therapy.