Tangshen Formula alleviates inflammatory injury against aged diabetic kidney disease through modulating gut microbiota composition and related amino acid metabolism.

Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased Anaeroplasma and Barnesiella genera and decreased Romboutsia, Akkermansia, and Collinsella genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.

Tangshen formula protects against podocyte apoptosis via enhancing the TFEB-mediated autophagy-lysosome pathway in diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease and currently there are no specific and effective drugs for its treatment. Podocyte injury is a detrimental feature and the major cause of albuminuria in DN. We previously reported Tangshen Formula (TSF), a Chinese herbal medicine, has shown therapeutic effects on DN. However, the underlying mechanisms remain obscure. AIM OF THE STUDY: This study aimed to explore the protective effect of TSF on podocyte apoptosis in DN and elucidate the potential mechanism. MATERIALS AND METHODS: The effects of TSF were assessed in a murine model using male KKAy diabetic mice, as well as in advanced glycation end products-stimulated primary mice podocytes. Transcription factor EB (TFEB) knockdown primary podocytes were employed for mechanistic studies. In vivo and in vitro studies were performed and results assessed using transmission electron microscopy, immunofluorescence staining, and western blotting. RESULTS: TSF treatment alleviated podocyte apoptosis and structural impairment, decreased albuminuria, and mitigated renal dysfunction in KKAy mice. Notably, TSF extracted twice showed a more significant reduction in proteinuria than TSF extracted three times. Accumulation of autophagic biomarkers p62 and LC3, and aberrant autophagic flux in podocytes of DN mice were significantly altered by TSF therapy. Consistent with the in vivo results, TSF prevented the apoptosis of primary podocytes exposed to AGEs and activated autophagy. However, the anti-apoptosis capacity of TSF was countered by the autophagy-lysosome inhibitor chloroquine. We found that TSF increased the nuclear translocation of TFEB in diabetic podocytes, and thus upregulated transcription of its several autophagic target genes. Pharmacological activation of TFEB by TSF accelerated the conversion of autophagosome to autolysosome and lysosomal biogenesis, further augmented autophagic flux. Conversely, TFEB knockdown negated the favorable effects of TSF on autophagy in AGEs-stimulated primary podocytes. CONCLUSIONS: These findings indicate TSF appears to attenuate podocyte apoptosis and promote autophagy in DN via the TFEB-mediated autophagy-lysosome system. Thus, TSF may be a therapeutic candidate for DN.

Gene signatures to therapeutics: Assessing the potential of ivermectin against t(4;14) multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow. The translocation, (t)(4;14), results in high-risk MM with limited treatment alternatives. Thus, there is an urgent need for identification and validation of potential treatments for this MM subtype. Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets. AIM: To elucidate the molecular basis and search for potential effective drugs of t(4;14) MM subtype by employing a comprehensive approach. METHODS: The transcriptional signature of t(4;14) MM was sourced from the Gene Expression Omnibus. Two datasets, GSE16558 and GSE116294, which included 17 and 15 t(4;14) MM bone marrow samples, and five and four normal bone marrow samples, respectively. After the differentially expressed genes were identified, the Cytohubba tool was used to screen for hub genes. Then, the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Using the STRING database and Cytoscape, protein-protein interaction networks and core targets were identified. Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis, respectively. RESULTS: In this study, a total of 258 differentially expressed genes with enriched functions in cancer pathways, namely cytokine receptor interactions, nuclear factor (NF)-κB signaling pathway, lipid metabolism, atherosclerosis, and Hippo signaling pathway, were identified. Ten hub genes (cd45, vcam1, ccl3, cd56, app, cd48, btk, ccr2, cybb, and cxcl12) were identified. Nine drugs, including ivermectin, deforolimus, and isoliquiritigenin, were predicted by the Connectivity Map database to have potential therapeutic effects on t (4;14) MM. In molecular docking, ivermectin showed strong binding affinity to all 10 identified targets, especially cd45 and cybb. Ivermectin inhibited t(4;14) MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro. Furthermore, ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14) MM cells. CONCLUSION: Collectively, the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment, with ivermectin emerging as a potential therapeutic alternative.

Development of a knowledge-based healthcare-associated infections surveillance system in China.

BACKGROUND: In the modern era of antibiotics, healthcare-associated infections (HAIs) have emerged as a prominent and concerning health threat worldwide. Implementing an electronic surveillance system for healthcare-associated infections offers the potential to not only alleviate the manual workload of clinical physicians in surveillance and reporting but also enhance patient safety and the overall quality of medical care. Despite the widespread adoption of healthcare-associated infections surveillance systems in numerous hospitals across China, several challenges persist. These encompass incomplete coverage of all infection types in the surveillance, lack of clarity in the alerting results provided by the system, and discrepancies in sensitivity and specificity that fall short of practical expectations. METHODS: We design and develop a knowledge-based healthcare-associated infections surveillance system (KBHAIS) with the primary goal of supporting clinicians in their surveillance of HAIs. The system operates by automatically extracting infection factors from both structured and unstructured electronic health data. Each patient visit is represented as a tuple list, which is then processed by the rule engine within KBHAIS. As a result, the system generates comprehensive warning results, encompassing infection site, infection diagnoses, infection time, and infection probability. These knowledge rules utilized by the rule engine are derived from infection-related clinical guidelines and the collective expertise of domain experts. RESULTS: We develop and evaluate our KBHAIS on a dataset of 106,769 samples collected from 84,839 patients at Gansu Provincial Hospital in China. The experimental results reveal that the system achieves a sensitivity rate surpassing 0.83, offering compelling evidence of its effectiveness and reliability. CONCLUSIONS: Our healthcare-associated infections surveillance system demonstrates its effectiveness in promptly alerting patients to healthcare-associated infections. Consequently, our system holds the potential to considerably diminish the occurrence of delayed and missed reporting of such infections, thereby bolstering patient safety and elevating the overall quality of healthcare delivery.

Pyrolysis temperature dependent effects of biochar on shifting fluorescence spectrum characteristics of soil dissolved organic matter under warming.

Biochar generally shift the content and molecular composition of soil dissolved organic matter (DOM) which represent the reactive components and have essential roles in coupling elemental cycling in soil. However, it is not clear how the effects of biochar on soil DOM composition is shifted under warming. This causes a knowledge gap to fully understand the fate of SOM affected by biochar application in a warming climate. To fill this gap, we conducted a simulated climate warming incubation of soil to study the influence of biochar with different pyrolysis temperatures and feedstock types on soil DOM components composition. Three-dimensional fluorescence spectrum analysis combining excitation emission matrix-parallel factor analysis (EEM-PARAFAC), fluorescence region integral (FRI), UV-vis spectrometry, principal component analysis (PCA), clustering analysis, Pearson correlation and multi-factor analysis of variance on fluorescence parameters (including FRI on Region I-V, FI, HIX, BIX, H/P) and soil DOC and DON content were analyzed for this purpose. Results showed that biochar shifted soil DOM composition and enhanced soil humification, which was dominantly pyrolysis-temperature dependent. Biochar shifted the soil DOM components composition probably through mediating soil microbial processing rather than direct input of their pristine DOM, and the influence of biochar on soil microbial processing was pyrolysis-temperature dependent and highly affected by warming. Medium-temperature biochar was more efficient for enhancing soil humification, by accelerating the transformation of protein-like components into humic-like components. Soil DOM composition presented a rapid response to warming, and long-term incubation may eliminate the effects of warming on shifting soil DOM composition. By revealing the heterogeneous effects of biochar with different pyrolysis temperatures on fluorescence characteristics of soil DOM components, our study provides a hint for the essential role of biochar on enhancing soil humification, and also suggests a vulnerability of biochar for soil carbon sequestration under warming.

Identification of immunity-related lncRNAs and construction of a ceRNA network of potential prognostic biomarkers in acute myeloid leukemia.

Objective: Using bioinformatics analyses, this study aimed to identify lncRNAs related to the immune status of acute myeloid leukemia (AML) patients and ascertain the potential impact in immunity-related competing endogenous RNA (ceRNA) networks on AML prognosis. Methods: AML-related RNA-seq FPKM data, AML-related miRNA expression microarray data, and gene sets associated with immunity-related pathways were, respectively, obtained from the TCGA, GEO, and ImmReg databases. An immunity-related ceRNA network was then constructed according to the predicted interactions between AML-related mRNAs, lncRNAs, and miRNAs. After performing LASSO and multivariate Cox regression analyses, lncRNAs in the ceRNA network were used to establish an AML prognostic model. According to mutual regulatory relationships and consistent trends of expression among candidate ceRNAs, two ceRNA subnetworks related to the AML prognostic model were determined. Finally, the correlation between the expression levels of mRNAs, lncRNAs, and miRNAs in each ceRNA subnetwork and immune cell infiltration (assessed by combining the ESTIMATE and CIBERSORT methods and ssGSEA) was analyzed. Results: A total of 424 immunity-related differentially expressed (IR-DE) mRNAs (IR-DEmRNAs), 191 IR-DElncRNAs, and 69 IR-DEmiRNAs were obtained, and a ceRNA network of 20 IR-DElncRNAs, 6 IR-DEmRNAs, and 3 IR-DEmiRNAs was established. Univariate Cox regression analysis was conducted on 20 IR-DElncRNAs, and 7 of these were identified to be significantly correlated with the overall survival (OS) time in AML patients. Then, two IR-DElncRNAs (MEG3 and HCP5) were screened as independent OS-related factors by LASSO and multivariable Cox regression analyses, and a prognostic model was constructed to evaluate the survival risk in AML patients. Survival analyses indicated that the OS of patients was often poor in the high-risk group. Additionally, from this model, two ceRNA regulatory pathways, namely, MEG3/miR-125a-5p/SEMA4C and HCP5/miR-125b-5p/IL6R, which were potentially involved in the immune regulation of AML prognosis were identified. Conclusion: lncRNAs HCP5 and MEG3 may act as key ceRNAs in the pathogenesis in AML by regulating immune cell representation as part of the regulatory lncRNA-miRNA-mRNA axes. The candidate mRNAs, lncRNAs, and miRNAs included in the ceRNA network identified here may serve as useful prognostic biomarkers and immunotherapeutic targets for AML.

Effect of open-wedge high tibial osteotomy and lateral patellofemoral retinacular release on patellar position: an X-ray imaging-based comparative study.

Background: Open-wedge high tibial osteotomy (OWHTO) may cause adverse changes in the mechanical environment of the patellofemoral joint. For patients with lateral patellar compression syndrome or patellofemoral arthritis, intraoperative management is still challenging. The effect of lateral retinacular release (LRR) on patellofemoral joint mechanics after OWHTO remains unclear. Our study aimed to evaluate the effect of OWHTO and LRR on the patellar position based on lateral and axial radiographs of the knee joint. Methods: The study comprised 101 knees (OWHTO group) undergoing OWHTO alone and 30 knees (LRR group) undergoing OWHTO and concomitant LRR. The following radiological parameters were statistically analyzed preoperatively and postoperatively: femoral tibial angle (FTA), medial proximal tibial angle (MPTA), weight-bearing line percentage (WBLP), Caton-Deschamps index (CDI), Insall-Salvati index (ISI), lateral patellar tilt angle (LPTA), and lateral patellar shift (LPS). The follow-up duration ranged from 6 to 38 months, with a mean of 13.51±6.84 months in the OWHTO group and 12.47±7.81 months in the LRR group. The Kellgren-Lawrence (KL) grading system was used to evaluate changes in patellofemoral osteoarthritis (OA). Results: Regarding the patellar height, preliminary analysis demonstrated a statistically significant decrease in the CDI and ISI in both groups (P<0.05). However, there was no significant difference in changes in CDI or ISI between the groups (P>0.05). In the OWHTO group, although there was a significant increase in the LPTA (P=0.033), the postoperative decrease in the LPS was not significant (P=0.981). In the LRR group, both the LPTA and LPS significantly decreased postoperatively (P=0.000). The mean changes in LPS were 0.03 mm in the OWHTO group and 1.44 mm in the LRR group, indicating a significant change in LPS (P=0.000). However, there was no significant difference in changes in LPTA between the groups, which was contrary to our expectations. Imaging showed no change in patellofemoral OA in the LRR group and progressive changes (from KL grade I to II) in patellofemoral OA in 2 (1.98%) patients in the OWHTO group. Conclusions: OWHTO can cause a significant decrease in patellar height and an increase in lateral tilt. LRR can significantly improve the lateral tilt and shift of the patella. The concomitant arthroscopic LRR should be considered for the treatment of patients with lateral patellar compression syndrome or patellofemoral arthritis.

Potential use of seaweed polysaccharides as prebiotics for management of metabolic syndrome: a review.

Seaweed polysaccharides (SPs) obtained from seaweeds are a class of functional prebiotics. SPs can regulate glucose and lipid anomalies, affect appetite, reduce inflammation and oxidative stress, and therefore have great potential for managing metabolic syndrome (MetS). SPs are poorly digested by the human gastrointestinal tract but are available to the gut microbiota to produce metabolites and exert a series of positive effects, which may be the mechanism by which SPs render their anti-MetS effects. This article reviews the potential of SPs as prebiotics in the management of MetS-related metabolic disturbances. The structure of SPs and studies related to the process of their degradation by gut bacteria and their therapeutic effects on MetS are highlighted. In summary, this review provides new perspectives on SPs as prebiotics to prevent and treat MetS.

Curcumol, a major terpenoid from Curcumae Rhizoma, attenuates human uterine leiomyoma cell development via the p38MAPK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age. Curcumae Rhizoma, the main essential oil component of which is curcumol, is widely used for the treatment of phymatosis in China due to its antitumor, anti-inflammatory, antithrombin, anti-tissue fibrosis and anti-oxygen pharmacological activities, but its potential for the treatment of UFs has not been evaluated. AIM OF THE STUDY: This study aimed to investigate the effects and mechanisms of curcumol intervention in human uterine leiomyoma cells (UMCs). MATERIALS AND METHODS: Putative targets of curcumol intervention in UFs were identified using network pharmacology strategies. Molecular docking was performed to assess the binding affinity of curcumol to core targets. A concentration gradient of curcumol (0, 50, 100, 200, 300, 400 and 500 µM) or RU-486 (mifepristone, 0, 10, 20, 40, 50, and 100 µM) was applied to UMCs, and cell viability was detected by the CCK-8 assay. Cell apoptosis and cell cycle were examined by flow cytometry, and cell migration was assessed by a wound-healing assay. Additionally, the mRNA and protein expression levels of critical pathway components were evaluated by RT‒PCR and western blotting. Finally, the actions of curcumol on different tumor cell lines were summarized. RESULTS: Network pharmacology predicted 62 genes with roles in the treatment of UFs with curcumol, and MAPK14 (p38MAPK) displayed a higher interaction degree. GO enrichment and KEGG analyses revealed that the core genes were abundantly enriched in the MAPK signaling pathway. The molecular binding of curcumol to core targets was relatively stable. In UMCs, 200, 300 and 400 µM curcumol treatment for 24 h decreased cell viability compared with that in the control group, and the greatest effect was detected at 48 h and maintained until 72 h. Curcumol arrested cells in the G0/G1 phase and subsequently suppressed mitosis, promoted early apoptosis and reduced the degree of wound healing in a concentration-dependent manner in UMCs. Furthermore, 200 µM curcumol decreased the mRNA and protein expression of p38MAPK, the mRNA expression of NF-κB, and the protein expression of Ki-67 and increased the mRNA and protein expression of Caspase 9. Curcumol (300 and 400 µM) decreased the mRNA and protein expression of p38MAPK, NF-κB, and Ki-67 and increased the protein expression of Caspase 9 in UMCs. Curcumol was demonstrated to treat tumor cell lines, including breast cancer, ovarian cancer, lung cancer, gastric cancer, liver cancer and nasopharyngeal carcinoma, but its effects on benign tumors have not yet been reported. CONCLUSION: Curcumol suppresses cell proliferation and cell migration while arresting the cell cycle in the G0/G1 phase and inducing cell apoptosis in UMCs via a mechanism related to p38MAPK/NF-κB pathway regulation. Curcumol may be a potential therapeutic and preventive agent in the treatment of benign tumors such as UFs.

Poricoic acid A suppresses renal fibroblast activation and interstitial fibrosis in UUO rats via upregulating Sirt3 and promoting ß-catenin K49 deacetylation.

Renal interstitial fibrosis is the common pathological process of various chronic kidney diseases to end-stage renal disease. Inhibition of fibroblast activation attenuates renal interstitial fibrosis. Our previous studies show that poricoic acid A (PAA) isolated from Poria cocos is a potent anti-fibrotic agent. In the present study we investigated the effects of PAA on renal fibroblast activation and interstitial fibrosis and the underlying mechanisms. Renal interstitial fibrosis was induced in rats or mice by unilateral ureteral obstruction (UUO). UUO rats were administered PAA (10 mg·kg-1·d-1, i.g.) for 1 or 2 weeks. An in vitro model of renal fibrosis was established in normal renal kidney fibroblasts (NRK-49F cells) treated with TGF-ß1. We showed that PAA treatment rescued Sirt3 expression, and significantly attenuated renal fibroblast activation and interstitial fibrosis in both the in vivo and in vitro models. In TGF-ß1-treated NRK-49F cells, we demonstrated that Sirt3 deacetylated ß-catenin (a key transcription factor of fibroblast activation) and then accelerated its ubiquitin-dependent degradation, thus suppressing the protein expression and promoter activity of pro-fibrotic downstream target genes (twist, snail1, MMP-7 and PAI-1) to alleviate fibroblast activation; the lysine-49 (K49) of ß-catenin was responsible for Sirt3-mediated ß-catenin deacetylation. In molecular docking analysis, we found the potential interaction of Sirt3 and PAA. In both in vivo and in vitro models, pharmacological activation of Sirt3 by PAA significantly suppressed renal fibroblast activation via facilitating ß-catenin K49 deacetylation. In UUO mice and NRK-49F cells, Sirt3 overexpression enhanced the anti-fibrotic effect of PAA, whereas Sirt3 knockdown weakened the effect. Taken together, PAA attenuates renal fibroblast activation and interstitial fibrosis by upregulating Sirt3 and inducing ß-catenin K49 deacetylation, highlighting Sirt3 functions as a promising therapeutic target of renal fibroblast activation and interstitial fibrosis.

[Effect of open wedge tibial high osteotomy on patella position and joint function].

OBJECTIVE: To investigate the effect of open wedge tibial high osteotomy on patella position, anterior knee pain and joint function. METHODS: From June 2016 to June 2021, 109 patients (111 knees) with medial knee osteoarthropathy treated by open wedge tibial high osteotomy were included according to the inclusion and exclusion criteria, including 41 males and 68 females;the age ranged from 38 to 78 years old with an average of(57.98±7.07) years;the course of disease ranged from 1 to 36 months with an average of (8.58±6.91) months. The femoral tibial angle(FTA), medial proximal tibial angle(MPTA), weight bearing line(WBL) percentage, Caton Deschamps index (CD index), lateral patella tilt angle (LPTA) and lateral patella shift (LPS) were observed and compared before and after operation. Lysholm score was used to evaluate the knee function, visual analogue scale(VAS) was used to evaluate the degree of anterior knee pain, and Kellgren Lawrence(K-L) grading system was used to evaluate the progress of patellofemoral osteoarthritis. RESULTS: All patients were followed up for 6 to 38 months with an average of (12.41±2.40) months. The preoperative FTA, MPTA, WBL percentage, CD index, and LPTA were significantly different from those at the last follow-up(P<0.05). There was no significant difference between before and after LPS operation(P=0.78). Lysholm score increased from (58.79±7.90) scores to (76.05±7.36) scores (P<0.05). The VAS of anterior knee pain decreased from (3.28±1.95) scores to(1.07±1.75) scores(P<0.05). Knee patellofemoral osteoarthritis showed progressive changes, but there was no significant difference in K-L grading before and after operation (P>0.05). CONCLUSION: After open wedge tibial high osteotomy, the position of patella is lowered and the patella is tilted outward, but the knee function and anterior knee pain are significantly improved. Adverse changes in patella position caused by open wedge tibial high osteotomy may not affect clinical outcomes.

Green edge emitting lasers with porous GaN cladding.

GaN lasers with green emission wavelength at λ = 510 nm have been fabricated using novel nano-porous GaN cladding under pulsed electrical injection. The low slope efficiency of 0.13 W/A and high threshold current density of 14 kA/cm2 are related to a combination of poor injection efficiency and high loss, analyzed by the independent characterization methods of variable stripe length and segmented contacts. Continuous wave operation showed narrowed spectra and augmented spontaneous emission.

Effect of platelet-rich plasma scaffolding combined with osteochondral autograft transfer for full-thickness articular cartilage defects of the femoral condyle.

We aimed to investigate the local application methods of platelet-rich plasma (PRP) and the effect and safety of PRP scaffolding combined with osteochondral autograft transfer (OAT) in the treatment of full-thickness articular cartilage defects of the femoral condyle. Patients with cartilage defects of the femoral condyle were treated with OAT combined with PRP scaffolding between July 2017 and December 2020. Preoperative magnetic resonance imaging (MRI) and computed tomography were utilized to assess the size, location, and severity of the osteochondral defects. X-ray and MRI images of the knee were obtained at the final follow-up to assess the osseointegration and integrity of the implanted articular cartilage. Osteoarthritic changes in the knee joint were evaluated using the Kellgren-Lawrence grading system. Clinical status was assessed using the visual analog scale (VAS), International Knee Documentation Committee (IKDC), and Lysholm scores before the treatment and at the final follow-up. Complications and patient satisfaction were recorded to assess the safety of this combination therapy. Twenty-one patients were recruited, with a mean follow-up duration of 18.23 ± 6.84 months. The mean lesion size was 2.3 ± 0.59 cm2. The mean platelet concentration in PRP at baseline was 6.27 ± 0.63 times greater than that in the peripheral blood. The VAS, IKDC, and Lysholm scores had improved significantly at the final follow-up (P< 0.001). No serious complications such as joint infection, deep venous thrombosis, or hematoma were observed. Eighteen patients (85.72%) were satisfied with their knee function and quality of life at the final follow-up. Three patients (14.28%) complained of mild anterior knee pain, which was relieved by oral administration of nonsteroidal anti-inflammatory drugs. MRI examinations of all patients showed bony consolidation and the defect surface was covered with cartilage-like tissue. X-ray evaluations indicated that osteoarthritis in two knees (9.5%) had progressed from grade 1 to grade 2 at the final follow-up. The preliminary results showed that OAT combined with PRP may be a safe and effective technique for the treatment of full-thickness articular cartilage defects in the knee.

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease.

Disturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an experimental DKD rat model induced by combining streptozotocin injection and unilateral nephrectomy, we employed untargeted metabolomics and 16S rRNA gene sequencing to explore the relationship between the metabolic profile and the structure and function of gut microbiota. Striking alterations took place in 140 serum metabolites, as well as in the composition and function of rat gut microbiota. These changes were mainly associated with carbohydrate, lipid, and amino acid metabolism. In these pathways, isomaltose, D-mannose, galactonic acid, citramalic acid, and prostaglandin B2 were significantly upregulated. 3-(2-Hydroxyethyl)indole, 3-methylindole, and indoleacrylic acid were downregulated and were the critical metabolites in the DKD model. Furthermore, the levels of these three indoles were restored after treatment with the traditional Chinese herbal medicine Tangshen Formula. At the genera level, g_Eubacterium_nodatum_group, g_Lactobacillus, and g_Faecalibaculum were most involved in metabolic disorders in the progression of DKD. Notably, the circulating lipid metabolites had a strong relationship with DKD-related parameters and were especially negatively related to the mesangial matrix area. Serum lipid indices (TG and TC) and UACR were directly associated with certain microbial genera. In conclusion, the present research verified the anomalous circulating metabolites and gut microbiota in DKD progression. We also identified the potential metabolic and microbial targets for the treatment of DKD.

The effect of low molecular weight-polycyclic aromatic hydrocarbons responsive hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 circuit on inflammatory response of A549 cells via the PI3K/AKT pathway and epithelial-mesenchymal transition process.

Inflammation is widely recognized as an essential inducer of epithelial-mesenchymal transition (EMT). Meanwhile, competitive endogenous RNA (ceRNA) has been involved in a variety of disease processes. Therefore, the aim of the current study is to explore the regulation of ceRNA in the PI3K/AKT pathway and EMT mechanism in inflammatory response caused by low molecular weight-polycyclic aromatic hydrocarbons (LMW-PAHs). The A549 cells were treated with an equal mixture of phenanthrene (Phe) and fluorene (Flu), and total RNA was extracted for transcriptome sequencing. The target regulation of ceRNA hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 was further determined for mechanism study. The mixture of Phe and Flu significantly upregulated the expressions of hsa_circ_0039929 and FGF2, down-regulated hsa-miR-15b-3p_R-1, activated the PI3K/AKT pathway and promoted EMT. Mechanically, the overexpression of hsa-miR-15b-3p_R-1 inhibited the expressions of hsa_circ_0039929 and FGF2, reversed the activation of PI3K/AKT signaling pathway by LMW-PAHs, and blocked the occurrence of EMT progression. Furthermore, knockdown of hsa_circ_0039929 could promote the levels of hsa-miR-15b-3p_R-1, while inhibit the expression of FGF2. The effects of hsa_circ_0039929 knockdowns on PI3K/AKT pathways and EMT progress resembled the hsa-miR-15b-3p_R-1 overexpression. All above suggested that ceRNA hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 played an important role in the inflammation and EMT caused by LMW-PAHs.

Suhuang Antitussive Capsule Ameliorates Corticosteroid Insensitivity in Cough Variant Asthma Guinea Pigs by Inhibiting p38 MAPK Signal Pathway.

Methods: The CVA guinea pig model was successfully established by use of ovalbumin (OVA) sensitization and cigarette smoke (CS) exposure. The guinea pigs were divided into 6 groups: a control group, an OVA model group, an OVA + CS model group, a Suhuang treatment group, a BUD treatment group, and a combination (Suhuang and BUD) treatment group. The effects of the treatment were determined by measuring lung function (RI/Cydn) and cough symptoms (coughs number/cough latency) as outcome criteria. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were determined by ELISA. Lung tissues were stained by hematoxylin and eosin (H&E). The expressions of GR/total p38 MAPK/p-p38 MAPK were detected by Western blot. The MKP-1 mRNA levels were detected by RT-PCR. Results: Combination treatment significantly decreased RI/coughs numbers and increased Cydn/cough latency. Significantly, the results indicated that combination treatment decreased injury to pulmonary tissues. Results also revealed that levels of inflammatory cytokines were reduced in all treatment groups but most markedly in the combination treatment group. Moreover, Suhuang treatment significantly ameliorated corticosteroid insensitivity by improving the expression of glucocorticoid receptors (GR). The expressions of total p38 MAPK and p-p38 MAPK in lung tissue were significantly inhibited in the Suhuang and combination treatment groups. The MKP-1 mRNA levels in Suhuang and combination treatment groups were also increased significantly. Conclusion: Suhuang was effective for reversing corticosteroid insensitivity by regulating the p38 MAPK signal pathway, and combining BUD and Suhuang treatment showed synergistic interactions in CVA guinea pigs. Our findings showed that this combination therapy might be a promising therapeutic agent for CVA and also clarified its underlying mechanism of action, providing a theoretical basis for clinical combination treatment with Suhuang and BUD in CVA patients.

Pseudotumor and delayed recurrent dislocation after total hip arthroplasty with a modular femoral neck: A case report.

RATIONALE: Pseudotumor formation after hip arthroplasty is a rare complication that can occur not only at the head-neck junction but also at the modular neck-stem junction. Dislocation is a challenging and common complication of primary and revision total hip arthroplasty compared with other complications. Similarly, the association between pseudotumors and delayed recurrent dislocation remains unclear. PATIENT CONCERNS: We report the case of a 73-year-old woman with pseudotumor formation after total hip arthroplasty combined with a modular femoral neck. A delayed recurrent dislocation occurred in this case. Approximately 4weeks after the first revision surgery, redislocation occurred. DIAGNOSIS: The patient was eventually diagnosed with delayed recurrent artificial hip dislocation combined with a periprosthetic pseudotumor of the right hip. INTERVENTIONS: During the first revision surgery, a thickened, indurated cyst measuring 8×3×8cm with a red-brown wall containing brown fluid was completely excised. A cemented stem, combined with a BIOLOX Forte ceramic head, was implanted. Approximately 4weeks after surgery, redislocation occurred, and we cemented an elevated rim liner on the acetabular component with a metal head. OUTCOMES: At the last follow-up, 49 months after revision surgery, the patient was asymptomatic with a Harris hip score of 90. The patient had a satisfactory prognosis after treatment. LESSONS: The application of the modular-neck stem should be cautiously performed, particularly for modular prostheses containing different alloys. Pseudotumors and insufficient soft-tissue tension both contribute to hip instability, which may eventually lead to delayed repeated dislocation. In addition, femoral offset must be considered. Cement-liner technology may be used for aging patients who are less active. This case report, focusing on pseudotumors and delayed recurrent dislocations, aimed to identify factors that may support this diagnosis, which is easy to miss. Consequently, it can provide further details on the treatment process and alert orthopedic surgeons to this infrequent but important cause of delayed recurrent dislocation.

Nano-porous GaN cladding and scattering loss in edge emitting laser diodes.

We report continuous wave operation of electrically injected InGaN laser diodes using nano-porous GaN n-side cladding with 33% porosity. At 454 nm emission wavelength, the pulsed injection slope efficiency is 0.24 W/A with a high loss of 82 cm-1. The considerable 60 cm-1 of excess loss of the nano-porous clad lasers is attributed to scattering at pores in unintentionally 3% porosified layers, supported by numerical modeling. Simulations comparing porous GaN cladding to AlInN cladding for lasers operating at 589 nm indicate that the porous cladding provides similar internal loss and lower thermal impedance.

Jolkinolide B alleviates renal fibrosis via anti-inflammation and inhibition of epithelial-mesenchymal transition in unilateral ureteral obstruction mice.

Renal fibrosis is a critical pathological process lead to a progressive loss of renal function. Jolkinolide B (JB) is a natural compound with anti-inflammatory activity from Euphorbia fischeriana Steud. The study evaluated the effect of JB on renal fibrosis in mice with unilateral ureteral obstruction (UUO). The results showed that JB could decrease renal fibrotic area, reduce phosphorylation of NF-κB p65 and the release of TNF-α, IL-6 and IL-1ß, restore the expression of vementin, α-SMA and E-cadherin, as well as TGF-ß1 and p-smad2/3. In conclusion, JB might reduce renal fibrosis by inhibiting inflammation induced by NF-κB pathway and EMT mediated by TGF-ß1/Smad pathway.