Efficacy of allogeneic tendon material coracoclavicular ligament reconstruction combined with Kirschner wire and titanium alloy hook plate material fixation in the treatment of acromioclavicular joint dislocation.

Objective: To compare the effects of allogeneic tendon coracoclavicular ligament reconstruction combined with Kirschner wire fixation and clavicular hook plate fixation on early postoperative pain, postoperative shoulder joint function score and shoulder joint mobility in patients with acromioclavicular joint dislocation. Methods: From January 2020 to January 2023, 43 patients with acromioclavicular joint dislocation admitted to Xi 'an Honghui Hospital were included. Among them, 24 patients were treated with the clavicular hook plate technique (Hook Plate,HP) group, and 19 patients were treated with allogeneic tendon coracoclavicular ligament reconstruction combined with the Kirschner wire technique (Allogeneic Tendon, AT) group. The Constant-Murley score of shoulder joint function 6 months after operation, postoperative shoulder joint activity, preoperative and postoperative pain, operation time, intraoperative blood loss and complications were compared between the two groups. Results: All 43 patients were followed up for an average of 9.7 (9-12) months. The intraoperative blood loss in the allogeneic tendon group was less than in the hook plate group. The Constant-Murley shoulder function score was higher than that in the hook plate group 6 months after the operation. The abduction and lifting activity was greater than that in the hook plate group. The visual analogue scale scores at 3 days and 14 days after operation were lower than those in the hook plate group. The difference was statistically significant (p < 0.001). There was 1 case (5.3%) of exudation around the Kirschner needle track in the allogeneic tendon reconstruction group, and 5 cases (20.8%) of complications in the hook plate group, including 1 case of internal fixation stimulation, 2 cases of acromion impingement syndrome, 1 case of acromioclavicular joint osteoarthritis, and 1 case of shoulder joint stiffness. The complication rate of the allogeneic tendon group was lower than that of the hook plate group. Conclusion: The clinical efficacy of allogeneic tendon coracoclavicular ligament reconstruction combined with Kirschner wire fixation in treating acromioclavicular joint dislocation (Rockwood type III-V) is better than hook plate internal fixation. The patients have less early postoperative pain and better recovery of shoulder joint function and shoulder joint mobility.

Wighteone, a prenylated flavonoid from licorice, inhibits growth of SW480 colorectal cancer cells by allosteric inhibition of Akt.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a frequently used herbal medicine worldwide, and is used to treat cough, hepatitis, cancer and influenza in clinical practice of traditional Chinese medicine. Modern pharmacological studies indicate that prenylated flavonoids play an important role in the anti-tumor activity of licorice, especially the tumors in stomach, lung, colon and liver. Wighteone is one of the main prenylated flavonoids in licorice, and its possible effect and target against colorectal cancer have not been investigated. AIM OF THE STUDY: This study aimed to investigate the anti-colorectal cancer effect and underlying mechanism of wighteone. MATERIALS AND METHODS: SW480 human colorectal cancer cells were used to evaluate the in vitro anti-colorectal cancer activity and Akt regulation effect of wighteone by flow cytometry, phosphoproteomic and Western blot analysis. Surface plasmon resonance (SPR) assay, molecular docking and dynamics simulation, and kinase activity assay were used to investigate the direct interaction between wighteone and Akt. A nude mouse xenograft model with SW480 cells was used to verify the in vivo anti-colorectal cancer activity of wighteone. RESULTS: Wighteone inhibited phosphorylation of Akt and its downstream kinases in SW480 cells, which led to a reduction in cell viability. Wighteone had direct interaction with both PH and kinase domains of Akt, which locked Akt in a "closed" conformation with allosteric inhibition, and Gln79, Tyr272, Arg273 and Lys297 played the most critical role due to their hydrogen bond and hydrophobic interactions with wighteone. Based on Akt overexpression or activation in SW480 cells, further mechanistic studies suggested that wighteone-induced Akt inhibition led to cycle arrest, apoptosis and autophagic death of SW480 cells. Moreover, wighteone exerted in vivo anti-colorectal cancer effect and Akt inhibition activity in the nude mouse xenograft model. CONCLUSION: Wighteone could inhibit growth of SW480 cells through allosteric inhibition of Akt, which led to cell cycle arrest, apoptosis and autophagic death. The results contributed to understanding of the anti-tumor mechanism of licorice, and also provided a rationale to design novel Akt allosteric inhibitors for the treatment of colorectal cancer.

Qi-dan-dihuang decoction ameliorates renal fibrosis in diabetic rats via p38MAPK/AKT/mTOR signaling pathway.

CONTEXT: Qi-dan-dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood. OBJECTIVE: This study reveals the mechanism by which QDD ameliorates DKD. MATERIALS AND METHODS: The compounds in QDD were identified by high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD-low (QDD-L), and 2% QDD-high (QDD-H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose-treated HK-2 and NRK-52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated. RESULTS: A total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial-mesenchymal transition (EMT) via the p38MAPK and AKT-mammalian target of rapamycin (mTOR) pathways. DISCUSSION AND CONCLUSION: QDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD.

Biomaterial-based mechanical regulation facilitates scarless wound healing with functional skin appendage regeneration.

Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages, ultimately impairing its normal physiological function. Accumulating evidence underscores the potential of targeted modulation of mechanical cues to enhance skin regeneration, promoting scarless repair by influencing the extracellular microenvironment and driving the phenotypic transitions. The field of skin repair and skin appendage regeneration has witnessed remarkable advancements in the utilization of biomaterials with distinct physical properties. However, a comprehensive understanding of the underlying mechanisms remains somewhat elusive, limiting the broader application of these innovations. In this review, we present two promising biomaterial-based mechanical approaches aimed at bolstering the regenerative capacity of compromised skin. The first approach involves leveraging biomaterials with specific biophysical properties to create an optimal scarless environment that supports cellular activities essential for regeneration. The second approach centers on harnessing mechanical forces exerted by biomaterials to enhance cellular plasticity, facilitating efficient cellular reprogramming and, consequently, promoting the regeneration of skin appendages. In summary, the manipulation of mechanical cues using biomaterial-based strategies holds significant promise as a supplementary approach for achieving scarless wound healing, coupled with the restoration of multiple skin appendage functions.

Macrophage barrier in the tumor microenvironment and potential clinical applications.

The tumor microenvironment (TME) constitutes a complex microenvironment comprising a diverse array of immune cells and stromal components. Within this intricate context, tumor-associated macrophages (TAMs) exhibit notable spatial heterogeneity. This heterogeneity contributes to various facets of tumor behavior, including immune response modulation, angiogenesis, tissue remodeling, and metastatic potential. This review summarizes the spatial distribution of macrophages in both the physiological environment and the TME. Moreover, this paper explores the intricate interactions between TAMs and diverse immune cell populations (T cells, dendritic cells, neutrophils, natural killer cells, and other immune cells) within the TME. These bidirectional exchanges form a complex network of immune interactions that influence tumor immune surveillance and evasion strategies. Investigating TAM heterogeneity and its intricate interactions with different immune cell populations offers potential avenues for therapeutic interventions. Additionally, this paper discusses therapeutic strategies targeting macrophages, aiming to uncover novel approaches for immunotherapy. Video Abstract.

Mulberry (Morus alba L.) leaf water extract attenuates type 2 diabetes mellitus by regulating gut microbiota dysbiosis, lipopolysaccharide elevation and endocannabinoid system disorder.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) leaf is a well-known herbal medicine and has been used to treat diabetes in China for thousands of years. Our previous studies have proven mulberry leaf water extract (MLWE) could improve type 2 diabetes mellitus (T2D). However, it is still unclear whether MLWE could mitigate T2D by regulating gut microbiota dysbiosis and thereof improve intestinal permeability and metabolic dysfunction through modulation of lipopolysaccharide (LPS) and endocannabinoid system (eCBs). AIM OF STUDY: This study aims to explore the potential mechanism of MLWE on the regulation of metabolic function disorder of T2D mice from the aspects of gut microbiota, LPS and eCBs. MATERIALS AND METHODS: Gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. LPS, N-arachidonoylethanolamine (AEA) and 2-ararchidonylglycerol (2-AG) contents in blood were determined by kits or liquid phase chromatography coupled with triple quadrupole tandem mass spectrometry, respectively. The receptors, enzymes or tight junction protein related to eCBs or gut barrier were detected by RT-PCR or Western blot, respectively. RESULTS: MLWE reduced the serum levels of AEA, 2-AG and LPS, decreased the expressions of N-acylphophatidylethanolamine phospholipase D, diacylglycerol lipase-α and cyclooxygenase 2, and increased the expressions of fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), alpha/beta hydrolases domain 6/12 in the liver and ileum and occludin, monoacylglycerol lipase and cannabinoid receptor 1 in the ileum of T2D mice. Furthermore, MLWE could change the abundances of the genera including Acetatifactor, Anaerovorax, Bilophila, Colidextribacter, Dubosiella, Gastranaerophilales, Lachnospiraceae_NK4A136_group, Oscillibacter and Rikenella related to LPS, AEA and/or 2-AG. Moreover, obvious improvement of MLWE treatment on serum AEA level, ileum occludin expression, and liver FAAH and NAAA expression could be observed in germ-free-mimic T2D mice. CONCLUSION: MLWE could ameliorate intestinal permeability, inflammation, and glucose and lipid metabolism imbalance of T2D by regulating gut microbiota, LPS and eCBs.

Selective Control of Phases and Electronic Structures of Monolayer TaTe2.

Transition metal dichalcogenide (TMDC) films exhibit rich phases and superstructures, which can be controlled by the growth conditions as well as post-growth annealing treatment. Here, the selective growth of monolayer TaTe2 films with different phases as well as superstructures using molecular beam epitaxy (MBE) is reported. Monolayer 1H-TaTe2 and 1T-TaTe2 films can be selectively controlled by varying the growth temperature, and their different electronic structures are revealed through the combination of angle-resolved photoemission spectroscopy measurements (ARPES) and first-principles calculations. Moreover, post-growth annealing of the 1H-TaTe2 film further leads to a transition from a 19 × 19 $\sqrt {19}{\times }\sqrt {19}$ superstructure to a new 2 × 2 superstructure, where two gaps are observed in the electronic structure and persist up to room temperature. First-principles calculations reveal the role of the phonon instability in the formation of superstructures and the effect of local atomic distortions on the modified electronic structures. This work demonstrates the manipulation of the rich phases and superstructures of monolayer TaTe2 films by controlling the growth kinetics and post-growth annealing.

Predicting the medium-temperature thermal stability of impact-strengthened medium-thick plate aluminum alloy using a back propagation artificial neural network.

A normalized medium-thick plate of aluminum alloy (4038) was impact-strengthened using a free-fall method at room temperature (approximately 20 °C). Specimens were then aged at 450 °C, 550 °C and 650 °C for 10, 20, 30 and 40 min respectively. Micro-hardness of each sample was tested. Micro-structure of samples annealed at 650 °C for different durations was characterized. A three-layer back propagation artificial neural network (BPANN) was trained using actual state parameters of the prepared samples. Results reveal that medium-temperature thermal stability of the prepared plate can be predicted through the BPANN model. Deviation of predicted values from the experimental ones is within 6 %, with a prediction accuracy exceeding 94 %. Variation trend of the predicted and the experimental thermal stability is consistent, but the predicted values are all higher than the measurements. Prediction accuracy of BPANN can be improved by increasing convergence rate of the error function. By adding relevant parameters of the micro-structure from samples aged at 650 °C to the input layer, BPANN model further improve its output and approach the real state of samples. The findings of this study can help researchers reduce the number and cost of experiments. The aim of this work was to predict the medium-temperature thermal stability of impact-strengthened normalized medium-thick plate of aluminum alloy annealed at different temperatures, and it also can be used as reference for other similar experiments.

Myricetin suppresses TGF-ß-induced epithelial-to-mesenchymal transition in ovarian cancer.

Background: Ovarian cancer (OC) is the second most common gynecological malignancy and has a high mortality rate. The current chemotherapeutic drugs have the disadvantages of drug resistance and side effects. Myricetin, a kind of natural compound, has the advantages of easy extraction, low price, and fewer side effects. Multiple studies have demonstrated the anti-cancer properties of myricetin. However, its impact on OC is still unknown and needs further investigation. Therefore, this study aimed to elucidate the mechanism by which myricetin suppresses transforming growth factor-ß (TGF-ß) -induced epithelial-to-mesenchymal transition (EMT) in OC through in vivo and in vitro experiments. Methods: In vitro experiments were conducted to evaluate the effects of myricetin on cell proliferation and apoptosis using CCK8 assay, plate clonal formation assay, and flow cytometry. Western blot was employed to evaluate the expression levels of caspase-3, PARP, and the MAPK/ERK and PI3K/AKT signaling pathways. Wound healing, transwell, western blot and immunofluorescence assay were used to detect TGF-ß-induced cell migration, invasion, EMT and the levels of Smad3, MAPK/ERK, PI3K/AKT signaling pathways. Additionally, a mouse xenograft model was established to verify the effects of myricetin on OC in vivo. Results: Myricetin inhibited OC proliferation through MAPK/ERK and PI3K/AKT signaling pathways. Flow cytometry and western blot analyses demonstrated that myricetin promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase-3 and the ratio of Bax/Bcl-2 in OC. Furthermore, myricetin suppressed the TGF-ß-induced migration and invasion by transwell and wound healing assays. Mechanistically, western blot indicated that myricetin reversed TGF-ß-induced metastasis through Smad3, MAPK/ERK and PI3K/AKT signaling pathway. In vivo, myricetin significantly repressed OC progression and liver and lung metastasis. Conclusion: Myricetin exhibited inhibitory effects on OC progression and metastasis both in vivo and in vitro. And it also reversed TGF-ß-induced EMT through the classical and non-classical Smad signaling pathways.

Efficacy comparison of Kirschner-wire tension band and anchor loop plate in treatment of olecranon fracture.

Objective: This study aimed to introduce a new surgical method for the fixation of olecranon fractures, and to compare the biomechanical stability and clinical efficacy of Kirschner wire tension band and anchor loop plate (ALP) in the treatment of olecranon fractures. Methods: A finite element model was established to analyze the mechanical properties of Kirschner wire tension and anchor loop plate fixation for olecranon fracture. The clinical data of 53 patients with olecranon fractures admitted to our hospital from March 2016 to October 2021 were retrospectively analyzed. Among them, 22 cases were fixed with an anchor loop plate (ALP group), and 31 patients were fixed with the Kirschner wire tension band technique. By reviewing the medical records and follow-up results, the final elbow mobility, secondary surgery, postoperative complications and elbow function recovery Mayo score and DASH score were compared between the two groups. Results: The biomechanical analysis of the finite element model showed that under the load of 120 N, the maximum displacement of the Kirschner wire group was 1.09 times that of the ALP group, the maximum stress of the Kirschner wire group was 1.33 times that of the ALP group, and the maximum stress of the olecranon proximal bone of the Kirschner wire group was 2.17 times that of the ALP group. Under the load of 200 N, the maximum displacement of the Kirschner wire group was 1.19 times that of the ALP group. The overall maximum stress of the Kirschner wire group was 1.59 times that of the ALP group, and the maximum stress of the proximal olecranon bone of the Kirschner wire group was 1.99 times that of the ALP group. The average follow-up time of the Kirschner wire and anchor loop plate groups was similar (p > 0.05). The average age of the two groups was identical (p > 0.05). The final elbow mobility in the anchor loop plate group was significantly greater than in the Kirschner wire group (p < 0.05). The Mayo score of the anchor loop plate group was substantially higher than that of the Kirschner wire group at 3 and 12 months after operation (p < 0.05), and the DASH score was significantly lower than that of the Kirschner wire group (p < 0.05). Postoperative complications in the two groups: 1 case (4.5%) in the anchor loop plate group had difficulties with internal fixation stimulation, and no infection occurred; in the Kirschner wire group, 5 cases (16.1%) had complications of internal fixation stimulation, and 1 patient (3.2%) had an infection. Conclusion: The model of olecranon fracture fixed by anchor loop plate and Kirschner wire tension technique was tested under 120 and 200 N tension, and no damage was found, indicating that the newly designed anchor loop plate was safe in mechanical structure. The biomechanical stability of the anchor plate technique is more stable, so it is not easy to have postoperative complications such as fracture block cutting and internal fixation failure. And the secondary operation rate and elbow function have better results. This technique is an effective method for the treatment of olecranon fractures.

Nanoscale multistate resistive switching in WO3 through scanning probe induced proton evolution.

Multistate resistive switching device emerges as a promising electronic unit for energy-efficient neuromorphic computing. Electric-field induced topotactic phase transition with ionic evolution represents an important pathway for this purpose, which, however, faces significant challenges in device scaling. This work demonstrates a convenient scanning-probe-induced proton evolution within WO3, driving a reversible insulator-to-metal transition (IMT) at nanoscale. Specifically, the Pt-coated scanning probe serves as an efficient hydrogen catalysis probe, leading to a hydrogen spillover across the nano junction between the probe and sample surface. A positively biased voltage drives protons into the sample, while a negative voltage extracts protons out, giving rise to a reversible manipulation on hydrogenation-induced electron doping, accompanied by a dramatic resistive switching. The precise control of the scanning probe offers the opportunity to manipulate the local conductivity at nanoscale, which is further visualized through a printed portrait encoded by local conductivity. Notably, multistate resistive switching is successfully demonstrated via successive set and reset processes. Our work highlights the probe-induced hydrogen evolution as a new direction to engineer memristor at nanoscale.

Oscillation of Electronic-Band-Gap Size Induced by Crystalline Symmetry Change in Ultrathin PbTe Films.

For the semiconductors of atomic length scales, even one atom layer difference could modify crystal symmetry and lead to a significant change in electronic structure, which is essential for modern electronics. However, the experimental exploration of such effect has not been achieved due to challenges in sample fabrication and characterization with atomic-scale precision. Here, we report the discovery of crystal symmetry alternation induced band-gap oscillation in atomically thin PbTe films by scanning tunneling microscopy. As the thickness of PbTe films is reduced from an 18- to 2-atomic layer, the band-gap size not only expands from 0.19 eV to 1.06 eV by 5.6 fold, but also exhibits an even-odd-layer oscillation, which is attributed to the alternating crystal symmetries between P4/mmm and P4/nmm. Our work sheds new light on electronic structure engineering of semiconductors at atomic scale for next-generation nanoelectronics.

Charge-State-Dependent Collision-Induced Dissociation Behaviors of RNA Oligonucleotides via High-Resolution Mass Spectrometry.

Mass spectrometry (MS)-based analysis of RNA oligonucleotides (oligos) plays an increasingly important role in the development of RNA therapeutics and epitranscriptomics research. However, MS fragmentation behaviors of RNA oligomers are understood insufficiently. Herein, we characterized the negative-ion-mode fragmentation behaviors of 26 synthetic RNA oligos containing four to eight nucleotides using collision-induced dissociation (CID) on a high-resolution, accurate-mass instrument. We found that in CID spectra acquired under the normalized collision energy (NCE) of 35%, approximately 70% of the total peak intensity was attributed to sequencing ions (a-B, a, b, c, d, w, x, y, z), around 25% of the peak intensity came from precursor ions that experienced complete or partial loss of a nucleobase in the form of either a neutral or an anion, and the remainder were internal ions and anionic nucleobases. The top five sequencing ions were the y, c, w, a-B, and a ions. Furthermore, we observed that CID fragmentation behaviors of RNA oligos were significantly impacted by their precursor charge. Specifically, when the precursors had a charge from 1- to 5-, the fractional intensity of sequencing ions decreased, while that of precursors that underwent either neutral or charged losses of a nucleobase increased. Additionally, we found that RNA oligos containing 3'-U tended to produce precursors with HNCO and/or NCO- losses, which presumably corresponded to isocyanic acid and cyanate anion, respectively. These findings provide valuable insights for better comprehending the mechanism behind RNA fragmentation by MS/MS, thereby facilitating the future automated identification of RNA oligos based on their CID spectra in a more efficient manner.

Nerve Injury-Induced γH2AX Reduction in Primary Sensory Neurons Is Involved in Neuropathic Pain Processing.

Phosphorylation of the serine 139 of the histone variant H2AX (γH2AX) is a DNA damage marker that regulates DNA damage response and various diseases. However, whether γH2AX is involved in neuropathic pain is still unclear. We found the expression of γH2AX and H2AX decreased in mice dorsal root ganglion (DRG) after spared nerve injury (SNI). Ataxia telangiectasia mutated (ATM), which promotes γH2AX, was also down-regulated in DRG after peripheral nerve injury. ATM inhibitor KU55933 decreased the level of γH2AX in ND7/23 cells. The intrathecal injection of KU55933 down-regulated DRG γH2AX expression and significantly induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. The inhibition of ATM by siRNA could also decrease the pain threshold. The inhibition of dephosphorylation of γH2AX by protein phosphatase 2A (PP2A) siRNA partially suppressed the down-regulation of γH2AX after SNI and relieved pain behavior. Further exploration of the mechanism revealed that inhibiting ATM by KU55933 up-regulated extracellular-signal regulated kinase (ERK) phosphorylation and down-regulated potassium ion channel genes, such as potassium voltage-gated channel subfamily Q member 2 (Kcnq2) and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in vivo, and KU559333 enhanced sensory neuron excitability in vitro. These preliminary findings imply that the down-regulation of γH2AX may contribute to neuropathic pain.

Analysis of risk factors for serous exudation of biodegradable material calcium sulfate in the treatment of fracture-related infections.

Objective: To explore the related risk factors of serous exudation after antibiotic-loaded calcium sulfate treatment of fracture-related infections and to provide a theoretical basis for clinical treatment and prevention of serous exudation complications. Methods: The clinical data of 145 patients with limb fracture-related infection treated with antibiotic-loaded calcium sulfate in Xi'an Honghui Hospital from January 2019 to December 2022 were retrospectively analyzed. All patients were diagnosed with fracture-related infection by preoperative magnetic resonance examination, bacterial culture and gene detection and received antibiotic-loaded calcium sulfate implantation. The postoperative serous exudation was recorded through hospitalization observation, outpatient review or follow-up. The collected clinical data were sorted out, and the patient data were divided into serous exudation groups and non-exudation groups. Firstly, the clinical data of the two groups were compared by single-factor analysis to screen out the risk factors. Then multivariate binary Logistic regression analysis determined the independent risk factors and protective factors. Results: 1) According to the inclusion and exclusion criteria, there were 145 cases with complete clinical data, including 27 cases in the non-infectious exudation group and 118 cases in the non-exudative group; 2) Univariate analysis showed that the history of diabetes, smoking history, calcium sulfate implantation, drainage time, combined flap surgery, geometric shape of implanted calcium sulfate, and thickness of soft tissue covered by the surgical area were all associated with the occurrence of non-infectious exudation after antibiotic-loaded calcium sulfate implantation (p < 0.05); 3) The amount of implanted calcium sulfate was more [OR = 5.310, (1.302-21.657), p = 0.020], combined with flap surgery [OR = 3.565, (1.195-10.641), p = 0.023], and the thickness of soft tissue coverage in the operation area was thinner [OR = 5.305, (1.336-21.057), p = 0.018]. Longer drainage time [OR = 0.210, (0.045-0.967), p = 0.045] was a protective factor for non-infectious exudation after antibiotic-loaded calcium sulfate implantation. Conclusion: 1) The probability of serous exudation in patients with fracture-associated infection after antibiotic-loaded calcium sulfate surgery was 18.62%. This complication may cause a heavier economic and psychological burden on patients; 2) With the increase of bone infection area and the application of more calcium sulfate, the incidence of serous exudation after antibiotic-loaded calcium sulfate surgery in patients with the fracture-related infection will increase, so we should use the amount of calcium sulfate reasonably on the premise of sufficient control of infection in clinical work, and the incidence of serous exudation will also increase due to the recent skin flap surgery and the thinner soft tissue coverage of calcium sulfate implantation area; 3) Under the premise of being able to drain the drainage from the surgical area, the longer drainage time of the drainage tube has a positive effect on preventing the occurrence of serous exudation.

The Correlation between Traditional Chinese Medicine Constitution and Hyperuricemia and Gout: A Systematic Review and Meta-Analysis.

Objective: To investigate the correlation between the constitution of traditional Chinese medicine (TCM) and hyperuricemia (HUA) and gout. Method: Databases including China National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database (VIP), China Biology Medicine Disc (CBMdisc), PubMed, The Cochrane Library, Web of Science, and Excerpta Medical Database (Embase) were searched to collect observational studies about TCM constitution in HUA and gout from inception to November 21, 2021. The distribution of TCM constitution types in HUA and gout patients was presented by proportion, while the correlation was presented by odds ratio (OR) and 95% CI. Meta-analysis was performed using StataCorp Stata (STATA) version 16.0 software. Results: Twenty-one cross-sectional studies and 10 case-control studies involving 38028 samples were included, among which 27526 patients were diagnosed with HUA and 2048 patients with gout. Phlegm-dampness constitution (PDC), damp-heat constitution (DHC), and qi-deficiency constitution (QDC) are the most common types, accounting for 24% (20%-27%), 22% (16%-27%), and 15% (12%-18%), respectively, in HUA patients, while DHC, PDC, and blood stasis constitution (BSC) accounted for 28% (18%-39%), 23% (17%-29%), and 11% (8%-15%), respectively, in gout patients. PDC and DHC were the main constitution types in patients with HUA or gout in south China, east China, north China, southwest China, northwest China, and northeast China. There was no difference in the distribution of PDC and QDC in male or female patients with HUA, while males with DHC in HUA were more common than females. The proportion of PDC or DHC among HUA patients was 1.93 times and 2.14 times higher than that in the general population (OR and 95% CI: 1.93 (1.27, 2.93), 2.14 (1.47, 3.13)), while the proportions of PDC, DHC, and BSC were 3.59 times, 4.85 times, and 4.35 times higher than that of the general groups (OR and 95% CI: 3.59 (1.65, 7.80), 4.85 (1.62, 14.57), and 4.35(2.33, 8.11)). Conclusion: PDC, DHC, and QDC are the main constitution types of patients with HUA, while PDC and QDC may be the risk factors for HUA. DHC, PDC, and BSC are the main constitution types of patients with gout, and they may be the risk factors for gout. In clinical and scientific research, more attention should be paid to the relationship between the above-mentioned TCM constitution in HUA or gout. Nevertheless, because the quality of the included observational studies is low, more prospective cohort studies related to TCM constitution and HUA or gout can be carried out to verify the causality between TCM constitution and HUA or gout.

Mulberry leaf water extract alleviates type 2 diabetes in mice via modulating gut microbiota-host co-metabolism of branched-chain amino acid.

Elevations in circling branched-chain amino acids (BCAAs) levels associated with insulin resistance and type 2 diabetes mellitus (T2DM). Morus alba L. water extracts (MLE) show hypoglycemic function, but the precise mechanism remains obscure. This study is designed to investigate the association of the antidiabetes effect of MLE with the BCAAs co-metabolism modulated by host and gut microbiota. Tissue-specific expressions of BCAA-catabolizing enzymes were detected by RT-PCR and western blot, respectively. The components of the intestinal microflora were analyzed by high-throughput 16S rRNA gene sequencing. The results showed that MLE administration improved blood glucose and insulin level, decreased inflammatory cytokines expression, and lowered serum and feces BCAAs levels. Furthermore, MLE reversed the abundance changes of the bacterial genera correlated with serum and feces BCAAs, such as Anaerovorax, Bilophila, Blautia, Colidextribacter, Dubosiella, Intestinimonas, Lachnoclostridium, Lachnospiraceae_NK4A136, Oscillibacter, and Roseburia. Functionality prediction indicated that MLE potentially inhibited bacterial BCAAs biosynthesis, and promoted the tissue-specific expression of BCAAs catabolic enzyme. More importantly, MLE had obvious impacts on BCAA catabolism in germ-free-mimic T2DM mice. Those results indicated that MLE improving T2DM-related biochemical abnormalities is associated with not only gut microbiota modification but also the tissue-specific expression of BCAAs catabolic enzyme.

Relationship between neutrophil/lymphocyte ratio and postoperative delirium in elderly patients with proximal femoral nail anti-rotation for intertrochanteric fractures.

OBJECTIVE: Delirium is a common postoperative complication in elderly patients with intertrochanteric femur fracture. This study aimed at analyzing risk factors for postoperative delirium (POD) in patients after proximal femoral nail anti-rotation (PFNA). METHODS: From February 2017 to February 2021, we included elderly patients with intertrochanteric fractures who underwent PFNA. The predictive ability and cut-off value of neutrophil/lymphocyte ratio (NLR) for POD were evaluated using receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were used to investigate the association between NLR and POD. RESULTS: We enrolled 315 patients. The ROC curve suggested that NLR ≥ 4.85 was the optimal cut-off value for POD. The POD and non-POD groups differed significantly in age, diabetes, time from injury to operation, preoperative albumin level, neutrophil count, and NLR (P < 0.05). Logistic regression indicated that NLR ≥ 4.85 (odds ratio [OR] = 3.491; 95% confidence interval [CI]: 1.731-5.982; P < 0.001), old age (OR = 1.921; 95% CI: 1.267-4.125; P < 0.001), time from injury to operation ≥ 48 h (OR = 1.733; 95% CI: 1.212-3.542; P = 0.007), and preoperative albumin level ≤ 35 g/L (OR = 2.274; 95% CI: 1.662-4.846; P = 0.001) increased the risk of POD. CONCLUSION: Old age, time from injury to operation ≥ 48 h, preoperative albumin level ≤ 35 g/L, and NLR ≥ 4.85 were independent risk factors for POD. Thus, NLR may predict POD in elderly patients with intertrochanteric femur fractures after PFNA.

Jiawei Yanghe Decoction suppresses breast cancer by regulating immune responses via JAK2/STAT3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Yanghe Decoction (JWYHD) is a widely used traditional Chinese medicine prescription in the clinical setting for the treatment of autoimmune diseases. Many studies showed that JWYHD has anti-tumor activities in cell and animal models. However, the anti-breast cancer effects of JWYHD and the underlying mechanisms of action remain unknown. AIM OF STUDY: This study aimed to determine the anti-breast cancer effect and reveal the underlying mechanisms of action in vivo, in vitro and in silico. MATERIALS AND METHODS: Orthotopic xenograft breast cancer mouse model and inflammatory zebrafish model were used to observe the anti-tumor effect and immune cell regulation of JWYHD. Moreover, the anti-inflammatory effect of JWYHD were evaluated by the expression of RAW 264.7 cells. JWYHD active ingredients were obtained by UPLC-MS/MS and potential targets were screened by network pharmacology. The therapeutic targets and signaling pathways predicted by computer were assessed by Western blot, real-time PCR (RT-PCR), immunohistochemistry (IHC) staining, and Enzyme-linked immunosorbent assays (ELISA) to explore the therapeutic mechanism of JWYHD against breast cancer. At last, Colivelin and Stattic were used to explore the effect of JWYHD on JAK2/STAT3 pathway. RESULTS: JWYHD significantly decreased the tumor growth in a dose-dependent manner in the orthotopic xenograft breast cancer mouse model. Flow cytometry and IHC results indicated that JWYHD decreased the expressions of M2 macrophages and Treg while increasing M1 macrophages. Meanwhile, ELISA and Western blot results showed a decrease in IL-1ß, IL-6, TNFα, PTGS2 and VEGFα in tumor tissue of JWYHD groups. The results were also verified in LPS-induced RAW264.7 cells and zebrafish inflammatory models. TUNEL assay and IHC results showed that JWYHD significantly induced apoptosis. Seventy-two major compounds in JWYHD were identified by UPLC-MS/MS and Network pharmacology. It was found that the significant binding affinity of JWYHD to TNFα, PTGS2, EGFR, STAT3, VEGFα and their expressions were inhibited by JWYHD. IHC and Western blot analysis showed that JWYHD could decrease the expression of JAK2/STAT3 pathway. Furthermore, Colivelin could reverse the decrease effect of JWYHD in vitro. CONCLUSION: JWYHD exerts a significant anti-tumor effect mainly by inhibiting inflammation, activating immune responses and inducing apoptosis via the JAK2/STAT3 signaling pathway. Our findings provide strong pharmacological evidence for the clinical application of JWYHD in the management of breast cancer.