Effect of a Percutaneous Screw Guide on Screw Placement for Posterior Talar Fractures.

AIM: This study aimed to evaluate the hypothesis that the utilization of percutaneous screw guides enhances the precision of screw placement in the surgical fixation of talar fractures. METHODS: Computed tomography (CT) scans of ankle joints were obtained from 40 healthy adults and 10 cadaveric specimens between April 2019 and August 2020 at Ningbo No. 6 Hospital. The acquired CT data were imported into Materialise Interactive Medical Image Control System (MIMICS) software for processing. Three-dimensional (3D) digital models of the ankle joints were reconstructed, and relevant anatomical parameters were measured. A percutaneous screw guide (PSG) was designed and fabricated to facilitate accurate screw placement in the posterior talar process. Ten eligible cadaveric ankle joints were selected for further analysis and their 3D models were reconstructed using the MIMICS software. Screw trajectory parameters were then measured and analyzed based on these cadaveric models, forming the model group for comparative analyses. Ten cadaveric specimens were utilized in this study, equally divided into two groups: a guider group (n = 5) and a free-hand group (n = 5). In the guider group, talar posterior process screws were inserted using percutaneous screw guidance. In the free-hand group, screws were inserted into the talar posterior process without guidance. Post-operative CT scans were performed on all specimens. The following parameters were quantitatively compared between the two groups: screw trajectories, entry point distances in specimens with preselected screws, entry point distance trajectories in the 3D model, operation time, frequency of fluoroscopic imaging, and number of drilling attempts. RESULTS: Following the generation of the 3D models from 10 cadavers, a virtual screw was digitally inserted into each model. In the model group, the preselected screw trajectory was oriented towards the medial aspect of the talar neck base, with a cephalad inclination angle (CIA) of 3.1° ± 1.5° in the transverse~plane and a medial diverge angle (MDA) of 12.0° ± 1.4° in the coronal plane. The CIA and MDA of the screw trajectory in the guider group were 2.1° ± 1.7° and 11.2° ± 1.6°, respectively, whereas the CIA and MDA in the free-hand group were 6.0° ± 2.2° and 18.8° ± 1.6°, respectively. Statistical analysis revealed significant differences in both CIA and MDA between the two groups (p < 0.05). Furthermore, the guider group yielded superior outcomes in terms of entry point distance, operation time, fluoroscopic exposure time, and number of drilling attempts compared to the free-hand group (p < 0.05). CONCLUSIONS: Percutaneous screw guidance can improve the accuracy and safety of the posterior process of the talar screws, which can be feasible for percutaneous fixation. Further studies are required to confirm the efficacy and clinical outcomes of percutaneous screw guidance.

Wetting State Transition of Laser Direct Writing Aluminum Surface Based on Coupling Effect of Micro/Nanoscale Characteristics.

Micro/nanostructured metal surfaces fabricated by laser direct writing (LDW) have been widely used in wettability-related fields. Previous studies focused on the effects of surface structural patterns or chemical composition on wettability, while the coupling mechanism and respective contributions of the two are not distinct. This paper reveals the coupling effect of micro/nanoscale characteristics on the wettability of LDW aluminum surfaces and elucidates the transition mechanism between wetting states on the surfaces with linear laser energy density. Through the contact angle experiments, a wetting state transition of the LDW surface is found from a more hydrophilic than pristine rose petal effect to lotus effect. Based on the bionic analysis method of the superhydrophobicity factors of lotus leaves, the contributions to the wettability of LDW surfaces are divided into the micro/nanoscale characteristics. The theoretical model for identifying the wetting state of a rough surface is proposed. Based on this model, the average Young's contact angle, θ̅Y, is calculated, which indicates the contribution of the nanoscale characteristics. During the transition process from rose petal effect to lotus effect, θ̅Y > 90° is a necessary condition for detachment from the rose petal effect, which is contributed by the high specific surface organic adsorption at the nanoscale. What is more, the wetting state determined by the microscale characteristics further enhances its hydrophobicity, leading to the lotus effect. Based on the wetting state identification model and the Cassie-Baxter equation, the change of micro/nanoscale characteristics on aluminum surfaces after LDW treatment is presented, and the influence of micro/nanoscale characteristics on the wetting state is decoupled and quantified. This research helps to coordinate the effects of surface structure and chemical composition on wettability in the design of specific wettability functional surfaces and can also be applied to other high heat density surface processing fields.

Microbial metabolite butyrate modulates granzyme B in tolerogenic IL-10 producing Th1 cells to regulate intestinal inflammation.

CD4+ T cells play a critical role in regulating autoimmune diseases, and intestinal microbial metabolites control various immune responses. Granzyme B (GzmB)-producing CD4+ T cells have been recently reported to participate in the pathogenesis of autoimmune diseases. Here, we found that GzmbB-deficient CD4+ T cells induced more severe colitis in Rag1-/- mice than wild-type (WT) CD4+ T cells. Germ-free (GF) mice exhibited a lower expression of GzmB in intestinal CD4+ T cells compared to specific pathogen-free (SPF) mice. Intestinal microbial metabolite butyrate increased GzmB expression in CD4+ T cells, especially in IL-10-producing Th1 cells, through HDAC inhibition and GPR43, but not GPR41 and GPR109a. Butyrate-treated GzmB-deficient CD4+ T cells demonstrated more severe colitis compared to butyrate-treated WT CD4+ T cells in the T cell transfer model. Butyrate altered intestinal microbiota composition, but altered microbiota did not mediate butyrate induction of intestinal CD4+ T cell expression of GzmB in mice. Blimp1 was involved in the butyrate induction of GzmB in IL-10-producing Th1 cells. Glucose metabolism, including glycolysis and pyruvate oxidation, mediated butyrate induction of GzmB in Th1 cells. In addition, we found that IKZF3 and NR2F6 regulated GzmB expression induced by butyrate. Together, our studies underscored the critical role of GzmB in mediating gut bacterial metabolite butyrate regulation of T cell tolerance at the mucosal surface.

Downregulation of Setdb2 promotes alternative activation of macrophages via the PI3K/Akt pathway to attenuate NAFLD after sleeve gastrectomy.

Non-alcoholic fatty liver disease (NAFLD) stands as the most prevalent hepatic disorder, with bariatric surgery emerging as the most effective intervention for NAFLD remission. Sleeve gastrectomy (SG) has notably ascended as the predominant procedure due to its comparative simplicity and consistent surgical outcomes. Nonetheless, the underlying mechanisms remain unclear. In this study, we probed the therapeutic potential of SG for NAFLD induced by a high-fat diet (HFD) in mice, with a focus on its impact on liver lipid accumulation, macrophage polarization, and the role of the histone methyltransferase Setdb2. SG prompted significant weight loss, diminished liver size and liver-to-body weight ratio, and enhanced liver function, evidenced by reduced serum levels of triglycerides (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination confirmed a reduction in liver lipid accumulation. Additionally, flow cytometry unveiled an increased proportion of M2 macrophages and a decrease in Setdb2 expression was shown in the SG group, suggesting an association between Setdb2 levels and postsurgical macrophage polarization. Furthermore, the conditional knockout of Setdb2 in mice further mitigated HFD-induced steatosis and promoted the M2 macrophage phenotype. Mechanistically, Setdb2 knockout in bone marrow-derived macrophages (BMDMs) favored M2 polarization, with RNA sequencing and western blotting analyses corroborating the upregulation of the PI3K/Akt signaling pathway. The effects of Setdb2 on macrophage activation were nullified by the PI3K inhibitor LY294002, suggesting that Setdb2 facilitates alternative macrophage activation through the PI3K/Akt signaling pathway. These comprehensive findings underscore the potential of SG as a therapeutic intervention for NAFLD by regulating the critical function of Setdb2 in macrophage polarization and activation, thereby offering novel insights into NAFLD pathogenesis and therapeutic targets.

[Treatment of Tile type C pelvic ring fracture using orthopedic robot combined with Starr pelvis reduction frame].

OBJECTIVE: To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture. METHODS: From October 2019 to May 2021, 14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame, including 9 males and 5 females. The age ranged from 33 to 69 years. All the 14 patients had fresh closed fractures without femur, tibia and fibula fracture. Surgery was completed from 4 to 7 d after hospital admission. During the operation, the X-ray carbon bed was used, the pelvic ring was reduced by Starr pelvis reduction frame, and pelvic ring fracture was treated by orthopedic robot. Operation time, bleeding volume, fluoroscopy times of single screw placement, fracture reduction quality, affected limb function and complications were observed. Radiological reduction was evaluated using Matta scoring standard, and clinical efficacy was evaluated by Majeed pelvic function scoring system at the final follow-up. RESULTS: All of 14 patients successfully completed the operation, the operation time was 84 to 141 min, the bleeding volume was 20 to 50 ml, and the fluoroscopy times of single screw insertion was 4 to 9 times. All of 14 patients were followed up for 12 to 24 months. The healing time was 3 to 7 months. No complications such as fracture of internal fixation, screw loosening, infection and nerve injury were found. According to the evaluation criteria of Matta imaging reduction, 9 cases were excellent, 4 cases were good, and 1 case was fair. At the final follow-up, Majeed pelvic function scoring system was used:10 cases were excellent, 4 cases were good. CONCLUSION: The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple, time-saving, less trauma, less complications and effective.

Amelioration of NAFLD by sleeve gastrectomy-triggered hepatocyte regeneration in mice - experimental research.

BACKGROUND: Sleeve gastrectomy (SG) is known to alleviate non-alcoholic fatty liver disease (NAFLD) and restore liver function; however, its underlying mechanism remains unclear. MATERIALS AND METHODS: We investigated the effect of SG on the metabolic phenotype of diet-induced obese (DIO) mice. Postoperative stained liver images were analyzed to determine the hepatocyte proliferation phenotype. Single-cell RNA sequencing was used to characterize the regeneration signals of the liver after SG in DIO mice, and real-time quantitative reverse transcription PCR was performed to verify the above results. We employed Olink proteomics to capture serum element changes and investigated the role of Yes1 protein in liver regeneration and carcinogenesis through the Hippo-YAP pathway. DIO mice were treated with YAP inhibitor verteporfin after SG mice to clarify whether SG-induced liver regeneration is related to the YAP signaling pathway. RESULTS: SG significantly reduced NAFLD-associated dysfunction in hepatocytes and replaced them with fully functional hepatocytes, which have a high regenerative capacity across the entire liver. SG also enhanced the hepatic regenerative capacity, as demonstrated by SG combined with hepatic lobectomy in healthy mice. Yes1 protein was identified as the signaling molecule most closely related to classical regeneration signals. Our study showed that SG-enhanced proliferation and improved metabolism did not depend on YAP signaling. CONCLUSION: SG can enhance hepatic regenerative capacity and improve liver metabolism. This study provides a better understanding of the mechanisms underlying SG-induced metabolic improvements.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy: Familial aggregation of obesity.

BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.

Harnessing ResNet50 and SENet for enhanced ankle fracture identification.

BACKGROUND: Ankle fractures are prevalent injuries that necessitate precise diagnostic tools. Traditional diagnostic methods have limitations that can be addressed using machine learning techniques, with the potential to improve accuracy and expedite diagnoses. METHODS: We trained various deep learning architectures, notably the Adapted ResNet50 with SENet capabilities, to identify ankle fractures using a curated dataset of radiographic images. Model performance was evaluated using common metrics like accuracy, precision, and recall. Additionally, Grad-CAM visualizations were employed to interpret model decisions. RESULTS: The Adapted ResNet50 with SENet capabilities consistently outperformed other models, achieving an accuracy of 93%, AUC of 95%, and recall of 92%. Grad-CAM visualizations provided insights into areas of the radiographs that the model deemed significant in its decisions. CONCLUSIONS: The Adapted ResNet50 model enhanced with SENet capabilities demonstrated superior performance in detecting ankle fractures, offering a promising tool to complement traditional diagnostic methods. However, continuous refinement and expert validation are essential to ensure optimal application in clinical settings.

CREB3L4 promotes hepatocellular carcinoma progression and decreases sorafenib chemosensitivity by promoting RHEB-mTORC1 signaling pathway.

This study was designed to explore the roles of CREB3L4 in the pathogenesis and drug resistance of hepatocellular carcinoma (HCC). The proliferation of HCC lines was determined in the presence of CREB3L4 over-expression and silencing. Chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter assay were performed to screen the potential target of CREB3L4 on mTORC1. Xenografted tumor model was established to define the regulatory effects of CREB3L4 in the tumorigenesis. Then we evaluated the roles of CREB3L4 in chemosensitivity to sorafenib treatment. CREB3L4 significantly induced the HCC cell proliferation by modulating the activation of mTROC1-S6K1 signaling pathway via binding with RHEB promoter. Moreover, CREB3L4 dramatically inhibited the chemosensitivity to sorafenib treatment via up-regulating RHEB-mTORC1 signaling. CREB3L4 promoted HCC progression and decreased its chemosensitivity to sorafenib through up-regulating RHEB-mTORC1 signaling pathway, indicating a potential treatment strategy for HCC through targeting CREB3L4.

Stromal Cell Regulation of Intestinal Inflammatory Fibrosis.

Intestinal inflammatory fibrosis is a severe consequence of inflammatory bowel diseases (IBDs). There is currently no cure for the treatment of intestinal fibrosis in IBD. Although inflammation is necessary for triggering fibrosis, the anti-inflammatory agents used to treat IBD are ineffective in preventing the progression of intestinal fibrosis and stricture formation once initiated, suggesting that inflammatory signals are not the sole drivers of fibrosis progression once it is established. Among multiple mechanisms involved in the initiation and progression of intestinal fibrosis in IBD, stromal cells play critical roles in mediating the process. In this review, we summarize recent progress on how stromal cells regulate intestinal fibrosis in IBD and how they are regulated by focusing on immune regulation and gut microbiota. We also outline the challenges moving forward in the field.

Biomechanical insights into ankle instability: a finite element analysis of posterior malleolus fractures.

BACKGROUND: Posterior malleolus fractures are known to be associated with ankle instability. The complexities involved in obtaining precise laboratory-based spatial pressure measurements of the ankle highlight the significance of exploring the biomechanical implications of these fractures. METHODS: Finite element analysis was utilized to examine the stress distribution across the contact surface of the ankle joint, both in its natural state and under varied sagittal fracture line angles. The study aimed to identify stress concentration zones and understand the influence of sagittal angles on stress distribution. RESULTS: Three distinct stress concentration zones were identified on the ankle's contact surface: the anterolateral tibia, the anteromedial tibia, and the fracture line. The most significant stress was observed at the fracture line when a fracture occurs. Stress at the fracture line notably spikes as the sagittal angle decreases, which can potentially compromise ankle stability. Larger sagittal angles exhibited only minor stress variations at the contact surface's three vertices. It was inferred that sagittal angles below 60° might pose risks to ankle stability. CONCLUSIONS: The research underscores the potential implications of fractures on the stress profile of the ankle joint, emphasizing the role of the contact surface in ensuring stability. The identification of three zones of stress concentration and the influence of sagittal angles on stress distribution offers a valuable reference for therapeutic decision-making. Further, the study reinforces the importance of evaluating sagittal fracture angles, suggesting that angles below 60° may compromise ankle stability.

A Deep Learning-Based Algorithm for Identifying Precipitation Clouds Using Fengyun-4A Satellite Observation Data.

Rapid and accurate identification of precipitation clouds from satellite observations is essential for the research of quantitative precipitation estimation and precipitation nowcasting. In this study, we proposed a novel Convolutional Neural Network (CNN)-based algorithm for precipitation cloud identification (PCINet) in the daytime, nighttime, and nychthemeron. High spatiotemporal and multi-spectral information from the Fengyun-4A (FY-4A) satellite is utilized as the inputs, and a multi-scale structure and skip connection constraint strategy are presented in the framework of the algorithm to improve the precipitation cloud identification. Moreover, the effectiveness of visible/near-infrared spectral information in improving daytime precipitation cloud identification is explored. To evaluate this algorithm, we compare it with five other deep learning models used for image segmentation and perform qualitative and quantitative analyses of long-time series using data from 2021. In addition, two heavy precipitation events are selected to analyze the spatial distribution of precipitation cloud identification. Statistics and visualization of the experiment results show that the proposed model outperforms the baseline models in this task, and adding visible/near-infrared spectral information in the daytime can effectively improve model performance. More importantly, the proposed model can provide accurate and near-real-time results, which has important application in observing precipitation clouds.

GPR120 promotes neutrophil control of intestinal bacterial infection.

G-protein coupled receptor 120 (GPR 120) has been implicated in anti-inflammatory functions. However, how GPR120 regulates the neutrophil function remains unknown. This study investigated the role of GPR120 in the regulation of neutrophil function against enteric bacteria. 16S rRNA sequencing was used for measuring the gut microbiota of wild-type (WT) mice and Gpr120-/- mice. Citrobacter rodentium infection and dextran sulfate sodium (DSS)-induced colitis models were performed in WT and Gpr120-/- mice. Mouse peritoneal-derived primary neutrophils were used to determine the neutrophil functions. Gpr120-/- mice showed altered microbiota composition. Gpr120-/- mice exhibited less capacity to clear intestinal Citrobacter rodentium and more severe intestinal inflammation upon infection or DSS insults. Depletion of neutrophils decreased the intestinal clearance of Citrobacter rodentium. GPR120 agonist, CpdA, enhanced WT neutrophil production of reactive oxygen species (ROS) and extracellular traps (NETs), and GPR120-deficient neutrophils demonstrated a lower level of ROS and NETs. CpdA-treated neutrophils showed an enhanced capacity to inhibit the growth of Citrobacter rodentium, which was abrogated by the inhibition of either NETs or ROS. CpdA promoted neutrophil inhibition of the growth of commensal bacteria Escherichia coli O9:H4 and pathobiont Escherichia coli O83:H1 isolated from a Crohn's disease patient. Mechanically, mTOR activation and glycolysis mediated GPR120 induction of ROS and NETs in neutrophils. Additionally, CpdA promoted the neutrophil production of IL-17 and IL-22, and treatment with a conditioned medium of GPR120-activated neutrophils increased intestinal epithelial cell barrier functions. Our study demonstrated the critical role of GPR120 in neutrophils in protection against enteric bacterial invasion.

Intrinsic STING Switches off Pathogenetic Programs of Th1 Cells to Inhibit Colitis.

BACKGROUND & AIMS: T helper 1 (Th1) effector cells are implicated in inflammatory bowel disease. The stimulator of interferon genes (STING), an intracellular DNA sensor, has been shown to regulate infection and various cancers. However, whether and how intrinsic STING signaling in Th1 cells regulates colitis is still unknown. METHODS: Dextran sodium sulfate-induced colitis and wild-type/STING-deficient CD4+T cell adoptive transfer models were used to analyze the role of STING in regulating colitis. The effect of STING on Th1 cells was determined by flow cytometry, RNA sequencing, metabolic assays, and mitochondrial functions. 16S ribosomal RNA sequencing and germ-free mice were used to investigate whether the microbiota were involved. The in vivo effect of STING agonist in murine colitis was determined. The expression and role of STING in human T cells were also determined. RESULTS: Activation of STING transformed proinflammatory IFNγ+Th1 cells into IL-10+IFNγ+Th1 cells, which were dramatically less pathogenic in inducing colitis. STING promoted Th1 interleukin (IL)-10 production by inducing STAT3 translocation into nuclear and mitochondria, which promoted Blimp1 expression and mitochondrial oxidation, respectively. Blockade of glucose or glutamine-derived oxidation, but not lipid-derived oxidation, suppressed STING induction of IL-10. Gut microbiota were changed in STING-/- mice, but the altered microbiota did not mediate STING effects on intestinal CD4+T cell production of IL-10. Translationally, STING agonists suppressed both acute and chronic colitis. Intestinal STING+ CD4+T cells were increased in inflammatory bowel disease patients, and STING agonists upregulated IL-10 production in human CD4+T cells. CONCLUSIONS: These findings establish a crucial role of T cell-intrinsic STING in switching off the pathogenic programs of Th1 cells in intestinal inflammation.

STING Promotes Intestinal IgA Production by Regulating Acetate-producing Bacteria to Maintain Host-microbiota Mutualism.

BACKGROUND: Intestinal Immunoglobulin A (IgA) is crucial in maintaining host-microbiota mutualism and gut homeostasis. It has been shown that many species of gut bacteria produce cyclic dinucleotides, along with an abundance of microbiota-derived DNA present within the intestinal lumen, which triggers the tonic activation of the cytosolic cGAS-STING pathway. However, the role of STING in intestinal IgA remains poorly understood. We further investigated whether and how STING affects intestinal IgA response. METHODS: Intestinal IgA was determined between wild-type (WT) mice and Sting-/- mice in steady conditions and upon enteric Citrobacter rodentium infection. STING agonists were used to stimulating B cells or dendritic cells in vitro. Gut microbiota composition was examined by 16S ribosomal RNA gene sequencing. Bacteria metabolomics functional analyses was performed by PICRUSt2. Fecal short-chain fatty acid (SCFA) was determined by Mass spectrometry and Cedex Bio Analyzer. Gut bacteria from WT mice and Sting-/- mice were transferred into germ-free mice and antibiotic-pretreated mice. RESULTS: Intestinal IgA response was impaired in Sting-/- mice. However, STING agonists did not directly stimulate B cells or dendritic cells to induce IgA. Interestingly, Sting-/- mice displayed altered gut microbiota composition with decreased SCFA-producing bacteria and downregulated SCFA fermentation pathways. Transfer of fecal bacteria from Sting-/- mice induced less IgA than that from WT mice in germ-free mice and antibiotic-pretreated mice, which is mediated by GPR43. Acetate, the dominant SCFA, was decreased in Sting-/- mice, and supplementation of acetate restored intestinal IgA production in Sting-/- mice. CONCLUSIONS: STING promotes intestinal IgA by regulating acetate-producing gut bacteria.

STING pathway contributes to maintaining a group of acetate-producing bacteria. STING regulates through these bacteria in a GPR43-dependent manner.

"In-Out-In" Percutaneous Reduction Technique for Treatment of Valgus-Impacted Femoral Neck Fractures: A Technical Trick and Case Series.

OBJECTIVE: Valgus-impacted femoral neck fractures with or without posterior tilt of the femoral head are very common and full of pitfalls in clinical practice, which may lead to femoral neck shortening (FNS) and avascular necrosis (AVN). The study tries to introduce a novel technical trick aiming at anatomical reduction of valgus-impacted femoral neck fracture with minimally invasive procedure, and summarize the clinical prognosis in case series. METHODS: In this retrospective study, 24 patients (seven men and 17 women) with valgus-impacted femoral neck fractures between May 2017 and July 2020 were managed by "in-out-in" percutaneous reduction technique (percutaneous reduction group). Another 24 cases (10 men and 14 women) suffering the fractures underwent in situ fixation were enrolled as control group for function comparison (in situ fixation group). All patients were followed up for 24-42 months. The clinical outcomes included complications after operations (χ2 test) and Harris Hip Score (HHS) for hip function (unpaired t test) in the two groups. The radiographic outcomes were evaluated by collodiaphyseal angle, posterior tilt angle, and FNS before the operation and during the follow-up in the percutaneous reduction group (unpaired t test). RESULTS: Patients' preoperative data, including age, sex, affected side, fracture types, and medical history, were similar between the two groups, respectively (p > 0.05). After surgery, the mean HHS at 6, 12, and 24 months were all better in the percutaneous reduction group (76 ± 6.72, 85.34 ± 6.33 and 90.54 ± 5.81) than that in the in situ fixation group (70.86 ± 6.91, 80 ± 6.11 and 84.1 ± 7.82), respectively (p < 0.05). One patient suffered fixation failure with screws retreat and one patient suffered AVN in the percutaneous reduction group. In the in situ fixation group, AVN occurred in two patients at last follow-up. There was no significant difference in complication amounts between the two groups (p > 0.05). In the percutaneous reduction group, collodiaphyseal angle, posterior tilt angle, and amount of FNS were significantly different between preoperative cases and immediately postoperative cases (p < 0.05). However, there was no statistical difference of the measurements among postoperative cases at different time points (within 24 h, 6 months, and 2 years postoperatively) (p > 0.05). CONCLUSIONS: Our experience of the technique and the case series show that "in-out-in" percutaneous reduction technique for treatment of valgus-impacted femoral neck fracture with or without posterior tilt of the femoral head is safe and effective for achieving successful bone union and satisfactory function.

Th17 Cell-Derived Amphiregulin Promotes Colitis-Associated Intestinal Fibrosis Through Activation of mTOR and MEK in Intestinal Myofibroblasts.

BACKGROUND & AIMS: Intestinal fibrosis is a significant complication of Crohn's disease (CD). Gut microbiota reactive Th17 cells are crucial in the pathogenesis of CD; however, how Th17 cells induce intestinal fibrosis is still not completely understood. METHODS: In this study, T-cell transfer model with wild-type (WT) and Areg-/- Th17 cells and dextran sulfate sodium (DSS)-induced chronic colitis model in WT and Areg-/- mice were used. CD4+ T-cell expression of AREG was determined by quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of AREG on proliferation/migration/collagen expression in human intestinal myofibroblasts was determined. AREG expression was assessed in healthy controls and patients with CD with or without intestinal fibrosis. RESULTS: Although Th1 and Th17 cells induced intestinal inflammation at similar levels when transferred into Tcrßxδ-/- mice, Th17 cells induced more severe intestinal fibrosis. Th17 cells expressed higher levels of AREG than Th1 cells. Areg-/- mice developed less severe intestinal fibrosis compared with WT mice on DSS insults. Transfer of Areg-/- Th17 cells induced less severe fibrosis in Tcrßxδ-/- mice compared with WT Th17 cells. Interleukin (IL)6 and IL21 promoted AREG expression in Th17 cells by activating Stat3. Stat3 inhibitor suppressed Th17-induced intestinal fibrosis. AREG promoted human intestinal myofibroblast proliferation, motility, and collagen I expression, which was mediated by activating mammalian target of rapamycin and MEK. AREG expression was increased in intestinal CD4+ T cells in fibrotic sites compared with nonfibrotic sites from patients with CD. CONCLUSIONS: These findings reveal that Th17-derived AREG promotes intestinal fibrotic responses in experimental colitis and human patients with CD. Thereby, AREG might serve as a potential therapeutic target for fibrosis in CD.

The low frequency pressure pulsation and control of the open-jet wind tunnel.

An open jet wind tunnel has low-frequency pressure pulsation in common wind speed range due to its unique structural form, which seriously damages the quality of flow field in the test section. The low-frequency pressure fluctuation performance and control mechanism of Jilin University open jet and return flow wind tunnel are investigated by experiments and numerical simulation. The results show that the low-frequency pressure fluctuation is a narrow pulse phenomenon that only occurs in certain intervals, and several velocity intervals may be found in the same wind tunnel. The reliability of the numerical simulation is verified by comparing the peak frequency and amplitude of pressure fluctuation in numerical simulation and wind tunnel tests. A simplified model similar to and amplifying the phenomenon is established. The flow structure and vortex evolution are analyzed via detached eddy simulation. In the test section, large-scale shedding vortices are formed at the nozzle exit, introducing periodic pulsating instantaneous velocity and acting with the collector to form an edge-feedback. This acoustic feedback forms resonance with the pipeline circuit, resulting in poor flow field quality. In accordance with the mechanism of nozzle jet, two methods of controlling pulsation are proposed: spoiler and flow-follow device. The study shows that the effects of two methods are abrupt, and the frequency of pressure pulsation is changed. The spoiler destroys the complete structure of vortex ring in free jet and develops into a complementary double vortex ring structure, which is highly sensitive to size factors. The flow-follow device supplements the velocity loss of the free jet at the nozzle and develops into a double vortex ring with master-slave structure in the middle of the test section. Its vibration reduction effect is greatly affected by the flow velocity. It takes effect in an appropriate range where the flow velocity is higher than the nozzle velocity. If the follow velocity is extremely low, the flow-follow device cannot change the original jet structure. If the follow velocity is extremely high, the momentum of the fan will be greatly reduced, the flow field will be unstable, and another order of pulsation may be induced. This work lays a solid foundation for further understanding the aerodynamic characteristics and optimization mechanism of open jet wind tunnel.

Glucose promotes regulatory T cell differentiation to maintain intestinal homeostasis.

Glucose, the critical energy source in the human body, is considered a potential risk factor in various autoimmune diseases when consumed in high amounts. However, the roles of glucose at moderate doses in the regulation of autoimmune inflammatory diseases and CD4+ T cell responses are controversial. Here, we show that while glucose at a high concentration (20% w/v) promotes intestinal inflammation, it suppresses colitis at a moderate dose (6% w/v), which increases the proportion of intestinal regulatory T (Treg) cells but does not affect effector CD4+ T cells. Glucose treatment promotes Treg cell differentiation but it does not affect Treg stability. Feeding glucose alters gut microbiota compositions, which are not involved in the glucose induction of Treg cells. Glucose promotes aryl hydrocarbon receptor (AhR) activation to induce Treg polarization. These findings reveal the different effects of glucose at different doses on the intestinal immune response.

[Staged operation for complex closed Pilon fracture].

OBJECTIVE: To explore clinical efficacy of staged surgery in treating complex closed Pilon fracture. METHODS: From June 2019 to January 2021, 29 patients with complex closed Pilon fracture were treated by staging surgery, including 18 males and 11 females, aged ranged from 31 to 68 years old with an average of (43.50±6.62) years old;7 cases were typeⅡand 22 cases were type Ⅲ according to Ruedi-Allgower classification. All patients had fresh closed fractures without talus and calcaneal fractures. The time from injury to closed reduction and external fixation, the interval between two stages of surgery, fracture healing time and complications were recorded. American Orthopedic Foot and Ankle Society(AOFAS) was used to assess clinical effects. Burwell-Charnley system was used to evaluate radiological reduction. RESULTS: All 29 patients were followed up from 13 to 30 months with an aver age of (15.43±5.31) months. All fractures healed well from 2 to 6 months with an average of (3.77±1.22) months. No internal fixation fracture, screw loosening, infection, internal fixation irritation, ankle stiffness occurred. The time from injury to closed reduction and cross-ankle fixation ranged from 1.22 to 7.34 h with an average of(2.31±3.52) h, the interval between two stages ranged from 5 to 9 days with an average of (5.98±2.11) days. AOFAS score was improved from 34.11±6.89 before operation to 90.10±10.11 after oepration at 12 months(P<0.05). According to AOFAS grading, 16 patients got excellent result, 9 good and 4 moderate. Fifteen patients got anatomic reduction, 12 patients were good reduction, and 2 cases were poor reduction according to Burwell-Charnley system. CONCLUSION: Staged surgery for complex closed Pilon fracture has advantages of less complications, statisfied reduction, stable fixation, which could obtain good recovery of ankle joint.