Frequency compensated diffusion model for real-scene dehazing.

Due to distribution shift, deep learning based methods for image dehazing suffer from performance degradation when applied to real-world hazy images. In this paper, this study considers a dehazing framework based on conditional diffusion models for improved generalization to real haze. First, our work finds that optimizing the training objective of diffusion models, i.e., Gaussian noise vectors, is non-trivial. The spectral bias of deep networks hinders the higher frequency modes in Gaussian vectors from being learned and hence impairs the reconstruction of image details. To tackle this issue, this study designs a network unit, named Frequency Compensation block (FCB), with a bank of filters that jointly emphasize the mid-to-high frequencies of an input signal. Our work demonstrates that diffusion models with FCB achieve significant gains in both perceptual and distortion metrics. Second, to further boost the generalization performance, this study proposed a novel data synthesis pipeline, HazeAug, to augment haze in terms of degree and diversity. Within the framework, a solid baseline for blind dehazing is set up where models are trained on synthetic hazy-clean pairs, and directly generalize to real data. Extensive evaluations on real dehazing datasets demonstrate the superior performance of the proposed dehazing diffusion model in distortion metrics. Compared to recent methods pre-trained on large-scale, high-quality image datasets, our model achieves a significant PSNR improvement of over 1 dB on challenging databases such as Dense-Haze and Nh-Haze.

Post-translational modification of CDK1-STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties.

BACKGROUND: Pancreatic cancer stem cells (CSCs) promote pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and chemoresistance. Cyclin-dependent kinase 1 (CDK1) plays an important role in tumor initiation in other tumors, but the function of CDK1 in PDAC remains unclear. Fisetin is a bioactive flavonoid with anti-tumor properties in multiple tumors, while its function in CSCs remains elusive. RESULTS: In this study, we demonstrated that CDK1 was correlated with prognosis and was highly expressed in pancreatic cancer tissue and gemcitabine-resistant cells. Silencing CDK1 impaired tumor stemness and reduced a subset of CSCs. We found that fisetin blocked the kinase pocket domain of CDK1 and inhibited pancreatic CSC characteristics. Using acetylation proteomics analysis and phosphorylation array assay, we confirmed that fisetin reduced CDK1 expression and increased CDK1 acetylation at lysine 33 (K33), which resulted in the suppression of CDK1 phosphorylation. Silencing CDK1 or STAT3 suppressed tumor stemness properties, while overexpressing CDK1 or STAT3 showed the opposite effect. Mutation or acetylation of CDK1 at K33 weakened STAT3 phosphorylation at Y705, impairing the expression of stem-related genes and pancreatic cancer stemness. In addition, lack of histone deacetylase 3 (HDAC3), which deacetylates CDK1, contributed to weakening STAT3 phosphorylation by regulating the post-translational modification of CDK1, thereby decreasing the stemness of PDAC. Moreover, our results revealed that fisetin enhanced the effect of gemcitabine through eliminating a subpopulation of pancreatic CSCs by inhibiting the CDK1-STAT3 axis in vitro and in vivo. CONCLUSION: Our findings highlight the role of post-translational modifications of CDK1-STAT3 signaling in maintaining cancer stemness of PDAC, and indicated that targeting the CDK1-STAT3 axis with inhibitors such as fisetin is a potential therapeutic strategy to diminish drug resistance and eliminate PDAC.

Functional Diversity of SIRT7 Across Cellular Compartments: Insights and Perspectives.

Posttranslational modifications (PTMs) play important roles in the regulation of protein function. Acetylation and deacetylation are among the most important PTMs. SIRT7 is a relatively understudied member of the sirtuin family, but recent studies have revealed that it plays a regulatory role in a variety of cellular activities, such as genome stabilization and repair, gene translation, ribosome production and other important processes. Here, we provide a list of the functions and mechanisms of SIRT7 in various organelles and show the important role of SIRT7 in maintaining normal cell function.

3-Methyladenine ameliorates surgery-induced anxiety-like behaviors in aged mice by inhibiting autophagy-induced excessive oxidative stress.

BACKGROUND: Postoperative anxiety is a common surgical complication in older patients. Research has recently linked excessive autophagy to several neurological disorders, including anxiety. This study aimed to determine whether 3-Methyladenine (3-MA) administration reduced anxiety-like behaviors in a mouse model following abdominal exploratory laparotomy. METHODS: An abdominal exploratory laparotomy model of postoperative anxiety was established using male C57BL/6 mice aged 20 months. 3-MA (6, 30, and 150 mg/ml) was administered via intracerebroventricular immediately following surgery. The mice were assessed 14 days after surgery using the marble burying, elevated plus maze tests, and local field potential recording in the amygdala. The levels of expression of phosphorylated-Akt, Beclin-1, LC3B, nuclear factor erythroid 2-related factor 2 (Nrf2)-occupied regions in NeuN-positive cells, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and glutathione (GSH) were measured at 24 h after surgery. RESULTS: The injection of 3-MA reversed the increased number of marbles buried, decreased time spent in the open arm, and enhanced θ oscillation power after 14 days of abdominal exploratory laparotomy. In addition, administration of 3-MA reduced the ratio of phosphorylated- to total-Akt, decreased expression in Beclin-1 and LC3B, attenuated MDA levels, and increased the ratio of Nrf2-occupied areas in NeuN-positive cells, SOD activity, and GSH levels under abdominal exploratory laparotomy conditions. CONCLUSIONS: 3-MA improved anxiety-like behaviors in aged mice undergoing abdominal exploratory laparotomy by inhibiting excessive autophagy-induced oxidative stress. These results suggest that 3-MA could be an effective treatment for postoperative anxiety.

Deciphering the pharmacological mechanisms of Rostellularia procumbens (L) Nees. Extract alleviates adriamycin-induced nephropathy in vivo and in vitro.

BACKGROUND: Rostellularia procumbens (L) Nees. is an effective traditional Chinese herbal medicine for the treatment of patients with chronic glomerulonephritis (CGN) in the clinic. However, the underlying molecular mechanisms need further elucidation. PURPOSE: This study aims to investigate the renoprotective mechanisms of n-butanol extract from Rostellularia procumbens (L) Nees. (J-NE) in vivo and in vitro. METHODS: The components of J-NE were analyzed by UPLC-MS/MS. In vivo, the nephropathy model was induced in mice by tail vein injection with adriamycin (10 mg·kg-1), and mice were treated with vehicle or J-NE or benazepril by daily gavage. In vitro, MPC5 cells exposed to adriamycin (0.3 µg/ml) were treated with J-NE. The effects of J-NE inhibit podocyte apoptosis and protect against adriamycin-induced nephropathy were determined by Network pharmacology, RNA-seq, qPCR, ELISA, immunoblotting, flow cytometry, and TUNEL assay, according to the experimental protocols. RESULT: The results showed that treatment significantly improved ADR-induced renal pathological changes, and the therapeutic mechanism of J-NE was related to the inhibition of podocyte apoptosis. Further molecular mechanism studies found that J-NE inhibited inflammation, increase the proteins expression levels of Nephrin and Podocin, reduce TRPC6 and Desmin expression levels and calcium ion levels in podocytes, and decrease the proteins expression levels of PI3K, p-PI3K, Akt and p-Akt to attenuated apoptosis. Furthermore, 38 compounds of J-NE were identified. CONCLUSION: J-NE exerted the renoprotective effects by inhibiting podocyte apoptosis, which provides effective evidence for the treatment of J-NE targeting renal injury in CGN.

Glycolysis, a new mechanism of oleuropein against liver tumor.

BACKGROUND: Benign and malignant liver tumors are prevalent worldwide. However, there is no effective and comprehensive treatment option for many patients with malignant tumors. Thus, it is critical to prevent benign tumors from worsening, increasing the number of treatment options and effective medications against malignant liver tumors. Oleuropein is a natural and non-toxic product and inhibits tumor growth in various ways. METHODS: We employed bioinformatics analysis and molecular docking to identify potential targets of oleuropein. Surface plasmon resonance (SPR) was used to determine the direct binding strength of the target and compounds. Essential functionalities of the targets were analyzed using gene interference approaches. Transcriptomic studies were performed to observe the global genomic alterations occurring inside cells. Changes in glycolytic metabolites and gene and protein expressions were also detected. The anti-tumor benefits of oleuropein in vivo were determined using a tumor-bearing mouse model. RESULTS: Glucose-6-phosphate isomerase (GPI) was found to be a direct target of oleuropein. GPI discontinuation in liver tumor cells altered the expression of many genes, causing glycogenolysis. GPI interference was associated with PYGM and PFKFB4 inhibitors to inhibit glycolysis in liver tumors. Oleuropein inhibited glycolysis and showed good anti-tumor activity in vivo without adverse side effects. CONCLUSIONS: GPI is a crucial enzyme in glycolysis and the immediate target of oleuropein. GPI expression inside tumor cells affects different physiological functions and signal transduction. Oleuropein has depicted anti-tumor action in vivo without harmful side effects. Moreover, it can control tumor glycolysis through GPI.

Lamina Variation and Its Relationship with Sedimentary Facies in Alkaline Lacustrine, Permian Fengcheng Formation, Junggar Basin, Northwest China.

The Permian Fengcheng Formation in the Mahu Sag was deposited in a volcanic-alkaline lacustrine evaporative environment and contains a unique variety of fine-grained sediments. This study examines, at a millimeter-scale, the influence of sedimentary microfacies on variability of lamina quality in fine-grained sediments in the second member of the Fengcheng Formation (P1f2). The methods used include thin-section identification, X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy (SEM), nitrogen adsorption, and nuclear magnetic resonance (NMR). Six types of lamina were identified in two different lithofacies: fan-delta front facies (FDFF) and semideep/deep lacustrine facies (SDDLF). The laminae in FDFF are predominantly feldspar-quartz laminae (FQL), reedmergnerite laminae (RL), shortite laminae (SL), alkaline mineral laminae (AML), and chert laminae (CL). The laminae in SDDLF are predominantly FQL, RL, SL, CL, and dolomite laminae (DOL). Variations in reservoir quality, oil-bearing properties, and the fracability of laminae in different sedimentary facies are determined by the combined effects of lamina density, mineral composition, rock structure, organic matter abundance, and microfractures. Analysis of these factors indicates superior reservoir qualities in FDFF. In SDDLF, the pore structure is limited by high lamina density, chert content, and fine grain size with the NMR porosities of FQL, RL, SL, and CL being 1.32, 0.18, 0.84, and 0.39%, respectively. However, in FDFF, the combination of high organic matter content, feldspar, pyrite, and clay minerals has a superior effect on the organic matter and minerals deposited resulting in better pore structure and more storage space for shale oil. The NMR porosities of FQL, RL, SL, and CL are 2.81, 2.53, 1.80, and 1.12%, respectively. Overall, analysis of lamina variations and their relationships with sedimentary facies indicates that the reservoir in FDFF may offer more favorable targets for "sweet spot" evaluation.

Can artificial ecological corridors be used for ecological restoration of cultivated land in Chinese Mollisols?

Artisficial ecological corridors (AECs) are internationally recognized as a standard method for restoring the regional ecological environment. However, the coupling relationship between AECs and soil quality has rarely been studied. Harbin, a typical mollisols region in the cold area of China, has severe soil problems and remediation is urgently needed, yet AEC research in this region is lacking. Based on the perspective of soil restoration, the construction factors of ecological corridors are quantitatively evaluated. It can predict the long-term impact of AECs already built along Harbin's Ashi River on soil chemical indices. This research studied the ecological restoration of secondary woodland, cultivated land within the ecological corridor, and cultivated land outside the influence range of the corridor under the influence of continuous recovery time and different locations in the corridor (distance from the Ashe River). Soil samples were taken from 5 plots, with a total of 161 samples, and 12 indices of soil ecological characteristics were monitored. The result are as follows: It is believed that the quality restoration of mollisols through ecological corridors has great application potential. Based on the low-cost natural restoration of ecological corridors, the highest values of total phosphorus (TP) and soil organic matter (SOM) in soil indices were detected in corridors (restored for more than 10 years). In addition, after ten years of recovery, pH and electrical conductivity (EC) in the ecological corridor returned to normal from high levels in cultivated land that far exceeded the reference values. The recovery process of mollisols mass begins to decrease, then increases, and finally reaches and exceeds the reference value of standard mollisols. The redundancy analysis of soil samples found the distance to be a key factor affecting soil total nitrogen (TN), SOM, and cation exchange capacity (CEC). Recovery time is a crucial factor affecting soil total organic carbon (SOC), pH and EC. According to the TN, SOM, and CEC mollisols indices, the ecological corridor's unilateral width is 125-150m. According to the SOC, pH, and EC indices of mollisols, the AECs should complete a natural recovery cycle of a minimum of 13 years. This study reveals the change mechanism of soil quality in mollisols area corridors based on recovery time and location. This research offer ideas and a scientific basis for worldwide governments in mollisols to formulate mollisols restoration policies.

Scopolin obtained from Smilax china L. against hepatocellular carcinoma by inhibiting glycolysis: A network pharmacology and experimental study.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax china L. is a well-known traditional medicinal plant. In China, it is a common anti-cancer drug that has been inherited for thousands of years. Some in vitro and in vivo studies have confirmed its potential lipid-lowering, anti-inflammatory and anti-ovarian cancer effects. However, there is no research on the material basis and mechanism of the rhizome of Smilax china L. against hepatocellular carcinoma. AIM OF THE STUDY: To explore the material basis and mechanism of scopolin from Smilax china L. against hepatocellular carcinoma. METHODS: The potential targets and active components of Smilax china L. against hepatocellular carcinoma were screened by transcriptomics, network pharmacology and molecular docking. Microscale Thermophoresis (MST) detection was used to verify the affinity of small molecule compounds with potential proteins and protein-protein interaction. The Extract from HepG2 cells was used to measure the expression of glycolysis-related proteins, glucose consumption and lactate production. The expression of apoptosis-related factors and glycolysis-related proteins in vivo was detected by immunohistochemistry. RESULTS: The glycolysis-related proteins glucose-6-phosphate isomerase (GPI), glycerol-3-phosphate dehydrogenase, mitochondrial (GPD2) and phosphoglycerate kinase 2 (PGK2) screened by transcriptomics, network pharmacology showed strongly binding with scopolin by molecular docking. MST detection has also verified the affinity of scopolin with GPI and GPD2. It was the first time found that Heat shock protein HSP 90-alpha (Hsp90α) bound strongly to GPI and GPD2 in the worldwide, while scopolin was able to affect the interaction between Hsp90α and GPD2. In vitro and in vivo experiments further demonstrated that scopolin may play an anti-cancer role by affecting the stability of tumor-associated proteins. The results showed that scopolin obtained from Smilax china L. could regulate the expression of GPI, GPD2 and PGK2 and inhibit the interaction of protein-protein, reduce the energy metabolism of tumor tissue, thereby inhibit tumor growth. CONCLUSION: Scopolin obtained from Smilax china L. plays the role of anti-hepatocellular carcinoma by regulating the expression of glycolysis proteins GPI, GPD2 and PGK2. Scopolin could affect the interaction between Hsp90α and GPD2 may provide a novel potential treatment direction for hepatocellular carcinoma.

Modulation effects of S vacancy and Mo edge on the adsorption and dissociation behaviors of toxic gas (H2S, SO2) molecules on the MoS2 monolayer.

This study focuses on the modulation effects of S vacancy and Mo edges on the adsorption and dissociation behaviors of toxic gases (H2S and SO2) on MoS2 by first-principles calculations. Both molecules are found to chemisorb at the S vacancy (SV) and pristine Mo edge and physisorb at the Mo edge with a 50% sulfur coverage (Mo-50 edge). Among them, SO2 has larger adsorption energy than H2S on both S vacancy and pristine Mo edge, which is related to a more electronegative O than S atom and electronically rich for the pristine Mo edge. The defective states of MoS2 induced by SV can be removed by forming Mo-S, Mo-O and Mo-H bonds upon the adsorption of SO2 and the dissociation of H2S, which is applicable in designing MoS2 based nano-electronics devices in the future. The dissociations of H2S and SO2 on pristine Mo edges are found to be more favorable than those on S vacancies due to the catalytically active Mo4+ states at edge sites. H2S is found to dissociate on the Mo-50 edge more easily than SO2. The adsorptions and dissociations of toxic gas on MoS2 with SV or Mo edges suggest MoS2 is a potential candidate in detecting and removal of toxic gases.

Quercitrin Attenuates Acetaminophen-Induced Acute Liver Injury by Maintaining Mitochondrial Complex I Activity.

The flavonoid quercitrin has a strong antioxidant property. It is also reported to have a protective effect on the liver. However, the mechanism by which it exerts a protective effect on the liver is not fully understood. The objective of this article is to confirm the protective effect of quercitrin extracted from Albiziae flos on acetaminophen (APAP)-induced liver injury and to explain its mechanism. In the in vivo study, quercitrin was administered orally to BALB/c mice at a dose of 50, 100, and 200 mg/kg for seven consecutive days. APAP (300 mg/kg) was injected intraperitoneally after a last dose of quercitrin was administered. Determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) levels showed that quercitrin effectively attenuated APAP-induced acute liver injury in mice. Results of the in vitro study showed that quercitrin reduced the levels of ROS, protected mitochondria from damage, and restored the activity of mitochondrial complex I in APAP-treated L-02 cells. The addition of rotenone which is an inhibitor of complex I blocked the protective effect of quercitrin. The expression of mitochondrial complex I was also maintained by quercitrin. Our results suggest that quercitrin can maintain the level of mitochondrial complex I in injured cells and restore its activity, which reduces the production of ROS, protects the mitochondria from oxidative stress, and has a protective effect on the liver.

Micro/Nanopore Systems in Lacustrine Tight Oil Reservoirs, China.

A nanoscale pore throat system develops extensively in rocks of unconventional reservoirs serving as both source and reservoir rock. The nanoscale pores provide the main storage spaces, accounting for 70% to 80% of the total unconventional tight reservoirs in China. As one of most important unconventional petroleum accumulations, tight oil has accumulated in more than 20 lacustrine strata since the Permian in China. Three types of tight oil reservoirs were identified based on the lithology and provenance in the lacustrine basins, including terrigenous sandstone, endogenous carbonate rocks and mixed sedimentary rocks. The micro/nanopore structures of these tight rocks were investigated with the application of optical microscopy, scanning electron microscopy (SEM), mercury injection capillary pressure (MICP), gas adsorption (GA) and nuclear magnetic resonance (NMR). The results indicated that the pore systems were connected by nanoscale throats dominated the storage spaces of the lacustrine tight oil reservoirs, while there were obvious differences among these three tight rocks, including pore types, pore size and movable fluid distribution. (i) The terrigenous sandstones, which were represented by the Triassic Chang 7 tight sandstones in the Ordos Basin and Cretaceous Quantou tight sandstones in the Songliao Basin, were mainly arkoses, and their storage space was mainly composed of dissolution pores and intraclay mineral pores. Feldspar, rock fragments and carbonate cements were the majority of the dissolved components, and the diameter of dissolution pores ranged from 1 micron to 50 microns. Abundant intrakaolinite and illite/smectite mixed layers pores were developed, and the pore size was 10 nm to 500 nm. The MICP and GA data suggested that storage spaces were connected by throats with diameters of 10 nm˜300 nm. (ii) The endogenous carbonate rocks, which were represented by the Jurassic Da'anzhai limestones in the Sichuan Basin, were the tightest rocks with porosities of less than 5% and permeabilities of less than 0.01×10-3 µm². The calcite dissolution pores and fractures with diameters of 10 nm˜500 nm were the most important storage spaces. The majority of pore systems were connected by throats with diameters of 6 nm˜100 nm based on the MICP and GA data. (iii) The tight mixed sedimentary rocks, which were represented by the Permian Lucaogou Formation in the Junggar Basin, were complex in lithologic composition, and dolostones and dolomite sandstones were the most important exploration targets. The interdolomite pores were the dominant storage spaces, in which abundant illite/smectite mixed layers were filled, and the pore size ranged from 50 nm to 50 microns. The MICP and GA data showed that the storage space was dominated by throats with diameters of 10 nm˜200 nm, and their volumetric contributions could reach over 70%. These results could provide a reference for future tight oil research and exploration in China.

Combined therapy of somatostatin analogues with pegvisomant for the treatment of acromegaly: a meta-analysis of prospective studies.

BACKGROUND: Acromegaly is a rare, chronic and severe disease. Drug therapy including somatostatin analogues (SAs), dopamine receptor agonists and growth hormone receptor antagonists (pegvisomant, PEG) are commonly used to treat patients who do not respond to surgery. The use of combination therapy with PEG and SAs has become more common over the last decade. We performed this study to accurately evaluate the effect of combination therapy of SAs with PEG on acromegalic patients. METHODS: PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science, Chinese Biomedical Literature Database and Trip database were searched for relevant studies. Prospective clinical trials treating acromegaly with the co-administration of SAs and PEG were included. We performed a meta-analysis by using Stata 12.1. Sensitivity analysis was conducted to explore heterogeneity. RESULTS: Nine studies were included in this meta-analysis. The overall rate of serum insulin-like growth factor 1 (IGF-1) normalization was 66% (95% CI: 52-78%; I2 = 62.59%). The combination therapy did not significantly change patients' fasting plasma glucose (ES: 0.011 mmol*L- 1; 95% CI: - 0.374 to 0.397 mmol*L- 1; P = 0.954) or glycosylated haemoglobin (ES: - 0.074%; 95% CI: - 0.166 to 0.315%; P = 0.544) while decreasing the fasting plasma insulin (ES: - 21.487 pmol*L-1; 95% CI: - 35.713 to - 7.260 pmol*L-1; P = 0.003). Elevation of liver enzyme levels was found in 14% (95% CI: 8 to 21%) of the patients. There was no significant difference for serious adverse events and treatment discontinuation due to adverse event between SAs monotherapy group and combination therapy group. CONCLUSIONS: Combined therapy of SAs and PEG effectively normalized IGF-1 levels in most of the patients whose IGF-1 level was greater than the upper limit of normal after high dose SAs monotherapy. The therapy also decreased significantly FPI levels with a neutral effect on glucose parameters in acromegaly patients. Moreover, elevated liver enzyme levels were observed in a small number of patients, which suggests a need for liver function monitoring. TRIAL REGISTRATION: We have our protocol registered in PROSPERO. (Registration number: CRD42019115549 ).

Subtrochanteric Osteotomy in Direct Anterior Approach Total Hip Arthroplasty.

Subtrochanteric osteotomy of the femur (STO) is a valuable corrective procedure in hip surgeries. However, STO in traditional posterolateral approach usually encounters complications such as postoperative dislocation, bone non-union, and prosthesis failure. Some relevant pathologies and mechanisms have been identified, but there is sparse evidence for verification. The aim of this video in orthopaedic technique is to test our hypothesis of STO in direct anterior approach to total hip arthroplasty in a complicated hip surgery, and to further illustrate the rationality, reproducibility, and superiority of STO in this minimally invasive and enhanced-recovery approach by presenting a standardized and systemic protocol, as well as operational pearls and pitfalls.

Direct Anterior Approach in Crowe Type III-IV Developmental Dysplasia of the Hip: Surgical Technique and 2 years Follow-up from Southwest China.

OBJECTIVES: To summarize our pioneering surgical practice and clinical outcome of Crowe type III-IV developmental dysplasia of the hip (DDH) with a direct anterior approach total hip arthroplasty in a single teaching hospital in Southwest China. METHODS: Fourteen patients (15 hips) diagnosed with Crowe type III-IV developmental dysplasia of the hip were involved in this single-center retrospective study between 2016 and 2018. A comprehensive surgical procedure, including preoperative planning and algorithms for leg length equalization, intraoperative stepwise soft tissue release, bone defect reconstruction, and an innovative subtrochanteric osteotomy, was described. Furthermore, advancements in intraoperative CT guidance, computer navigation, and nerve monitoring were available for specific demands. The short-term clinical outcome was evaluated at the endpoint of follow-up by three patient-reported functional scales (Harris, WOMAC, and SF-12 scores), and objective data collected at the clinic, including functional recovery (muscle strength of hip flexor and abductor, correction of the pelvic tilt, leg length discrepancy, and limp), radiographic analysis, and complication occurrence. RESULTS: The intraoperative variables were carefully recorded. The mean operating times in Crowe type III and IV groups were 115.8 min and 156.2 min, and the median blood loss volumes were 520.5 mL and 810.2 mL, respectively. The general changes in the Harris, SF-12, and WOMAC scores of the two groups were 46.2, 8.7 and 134.3, respectively, at a mean follow-up of 25.4 months. Enhanced recovery of hip abductor muscle strength was identified in 85.7% of the population at the third postoperative month. The equalization of leg length and correction of the pelvic tile were observed at the sixth postoperative month, with a 36-mm decrease in leg length discrepancy. No radiographic evidence of the loosening or migration of the components was observed. A self-innovated subtrochanteric shortening osteotomy was performed in five patients, and they healed after 6 months. Specific complications included two cases of distal femoral cracks and one case of a periprosthetic fracture needing internal fixation. Two patients received a late iliotibial band release at the 3rd month postoperatively due to progressive genu valgum. No records of infection, dislocation, nerve palsy, bone non-union, or revision surgery were identified. DISCUSSION: The direct anterior approach total hip arthroplasty showed potential advantages, including optimum component positioning, improved hip stability, steerable complication rate, and enhanced functional recovery with Crowe type III-IV DDH. The short-term outcome is comparable to that of the traditional posterolateral approach.

Direct anterior approach total hip arthroplasty for Crowe III and IV dysplasia.

High-dislocated hip dysplasia is challenging to treat with total hip arthroplasty via the direct anterior approach (DAA). The DAA has potential advantages including optimizing component positioning, enhanced hip stability, and a more rapid postoperative recovery. We present a surgical technique for DAA total hip arthroplasty for hip dysplasia that includes preoperative planning, soft tissue releases, subtrochanteric osteotomy, component placement, and intraoperative nerve monitoring and imaging. This technique provides detailed technical instructions, specifically including pearls and pitfalls, and complication prevention strategies.

Esculetin Inhibits Cancer Cell Glycolysis by Binding Tumor PGK2, GPD2, and GPI.

Glycolysis can improve the tolerance of tissue cells to hypoxia, and its intermediates provide raw materials for the synthesis and metabolism of the tumor cells. If it can inhibit the activity of glycolysis-related enzymes and control the energy metabolism of tumor, it can be targeted for the treatment of malignant tumor. The target proteins phosphoglycerate kinase 2 (PGK2), glycerol-3-phosphate dehydrogenase (GPD2), and glucose-6-phosphate isomerase (GPI) were screened by combining transcriptome, proteomics, and reverse docking. We detected the binding constant of the active compound using microscale thermophoresis (MST). It was found that esculetin bound well with three potential target proteins. Esculetin significantly inhibited the rate of glycolysis, manifested by differences of cellular lactate production and glucose consumption in HepG2 cells with or without esculetin. It was found that GPD2 bound strongly to GPI, revealing the direct interaction between the two glycolysis-related proteins. Animal tests have further demonstrated that esculetin may have anticancer effects by affecting the activity of PGK2, GPD2, and GPI. The results of this study demonstrated that esculetin can affect the glucose metabolism by binding to glycolytic proteins, thus playing an anti-tumor role, and these proteins which have direct interactions are potential novel targets for tumor treatment by esculetin.

Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect.

Albiziae Flos (AF) has been experimentally proven to have an antidepressant effect. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of action of AF in depression has not been completely deciphered. This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF. The methods included collection and screening of chemical components, prediction of depression-associated targets of the active components, gene enrichment, and network construction and analysis. Quercetin and 4 other active components were found to exert antidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand-receptor interaction pathways. DRD2, HTR1A, and SLC6A4 were identified as important targets of the studied bioactive components of AF. This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.

Efficacy and safety of ketoconazole combined with calmodulin inhibitor in solid organ transplantation: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Calcineurin inhibitors (CNIs) can significantly improve the results of solid organ transplantation regarding graft and patient survival. However, the high cost, chronic nephrotoxicity and other side effects are major challenges for the long-term use of these drugs. Ketoconazole can significantly increase the plasma concentration of CNIs by inhibiting the activity of the cytochrome P450 enzyme. The combination of ketoconazole-CNIs can reduce the cost of medication for patients by reducing the dosage of CNIs, but its safety is still controversial. Therefore, this study was designed to assess the safety and efficacy of this combination. METHODS: We performed a systematic literature search in PubMed, Embase, Cochrane Library and clinicaltrials.gov for randomized controlled trials on ketoconazole and CNI (cyclosporin or tacrolimus) co-administration in solid organ transplantation. Two authors independently selected studies, assessed the risk of bias and extracted data. The meta-analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration. PROSPERO registration number: CRD42019118796. RESULTS AND DISCUSSION: Five relevant trials with 326 patients were included. Compared with the controls, ketoconazole combined with CNIs can significantly reduce the dose of CNIs in patients receiving solid organ transplantation (WMD = -203.04 mg/day; 95% CI: -310.51 to -95.57, P = .0002). There was no significant difference in serum creatinine between the experimental group and the control group (WMD = -0.19 mg/mL; 95% CI: -0.52 to 0.14, P = .26). In addition, there was no significant difference in the number of rejections between the two groups (OR = 0.58; 95% CI: 0.27 to 1.22, P = .15). WHAT'S NEW AND CONCLUSION: The co-administration of ketoconazole and CNIs can significantly reduce the dose of CNIs. This combination may be safely used as a CNI-sparing agent from the time of solid organ transplantation with low-dose ketoconazole, based on the findings of this review.

Bioactive ingredients obtained from Cortex Fraxini impair interactions between FAS and GPI.

The high expression of fatty acid synthase (FAS) in tumor cells is consistent with their elevated requirement for fatty acids for cell membrane synthesis and energy supply to support their almost unlimited proliferation. The expression levels of FAS in tumor cells are related to their proliferation, invasion, and metastasis. This study investigated the possible bioactive ingredients (fraxin, esculetin, scopolin et al.) of Cortex Fraxini and their effects on the interaction between specific proteins. We used microscale thermophoresis (MST) to show that our target protein, FAS (screened by combining transcriptome and network pharmacology), bound to the active compounds in Cortex Fraxini. It was found that FAS bound strongly to Glucose-6-phosphate isomerase (GPI), and that scopolin could affect this interaction by proteomics and MST. The results of this study demonstrate that the active compounds in Cortex Fraxini could play an anti-tumor role by binding to FAS and inhibiting the interactions between FAS and GPI to affect glucose and lipid metabolism, and that the protein pathway is a potential novel target for tumor treatment.