THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma.

BACKGROUND: THOC7-AS1 and FSTL1 expression are frequently upregulated in cutaneous squamous cell carcinoma (cSCC). However, their molecular biological mechanisms remain elusive and their potential as therapeutic targets needs urgent exploration. METHODS: Human tissue samples were used to evaluate clinical parameters. In vitro and in vivo experiments assessed biological functions. Quantitative PCR, western blot, immunohistochemistry, immunocytochemistry, immunoprecipitation, RNA fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation, silver staining, chromatin immunoprecipitation, dual luciferase reporter assays etc. were utilized to explore the molecular biological mechanisms. RESULTS: We found FSTL1 is an oncogene in cSCC, with high expression in tumor tissues and cells. Its elevated expression closely associates with tumor size and local tissue infiltration. In vitro and in vivo, high FSTL1 expression promotes cSCC proliferation, migration and invasion, facilitating malignant behaviors. Mechanistically, FSTL1 interacts with ZEB1 to promote epithelial-to-mesenchymal transition (EMT) in cSCC cells. Exploring upstream regulation, we found THOC7-AS1 can interact with OCT1, which binds the FSTL1 promoter region and promotes FSTL1 expression, facilitating cSCC progression. Finally, treating tumors with THOC7-AS1 antisense oligonucleotides inhibited cSCC proliferative and migratory abilities, delaying tumor progression. CONCLUSIONS: The THOC7-AS1/OCT1/FSTL1 axis regulates EMT and promotes tumor progression in cSCC. This study provides clues and ideas for cSCC targeted therapy.

GBP1 promotes cutaneous squamous cell carcinoma proliferation and invasion through activation of STAT3 by SP1.

Cutaneous squamous cell carcinoma (cSCC) ranks as the second most prevalent skin tumour (excluding melanoma). However, the molecular mechanisms driving cSCC progression remain elusive. This study aimed to investigate GBP1 expression in cSCC and elucidate its potential molecular mechanisms underlying cSCC development. GBP1 expression was assessed across public databases, cell lines and tissue samples. Various assays, including clone formation, CCK8 and EdU were employed to evaluate cell proliferation, while wound healing and transwell assays determined cell migration and invasion. Subcutaneous tumour assays were conducted to assess in vivo tumour proliferation, and molecular mechanisms were explored through western blotting, immunofluorescence and immunoprecipitation. Results identified GBP1 as an oncogene in cSCC, with elevated expression in both tumour tissues and cells, strongly correlating with tumour stage and grade. In vitro and in vivo investigations revealed that increased GBP1 expression significantly enhanced cSCC cell proliferation, migration and invasion. Mechanistically, GBP1 interaction with SP1 promoted STAT3 activation, contributing to malignant behaviours. In conclusion, the study highlights the crucial role of the GBP1/SP1/STAT3 signalling axis in regulating tumour progression in cSCC. These findings provide valuable insights into the molecular mechanisms of cSCC development and offer potential therapeutic targets for interventions against cSCC.

Rapid Single-Round Pool Testing of Infectious Disease Enabled by Multicolor Digital Melting PCR.

Pooled nucleic acid amplification test is a promising strategy to reduce cost and resources for screening large populations for infectious disease. However, the benefit of pooled testing is reversed when disease prevalence is high, because of the need to retest each sample to identify infected individual when a pool is positive. Split, Amplify, and Melt analysis of Pooled Assay (SAMPA) is presented, a multicolor digital melting PCR assay in nanoliter chambers that simultaneously identify infected individuals and quantify their viral loads in a single round of pooled testing. This is achieved by early sample tagging with unique barcodes and pooling, followed by single molecule barcode identification in a digital PCR platform using a highly multiplexed melt curve analysis strategy. The feasibility is demonstrated of SAMPA for quantitative unmixing and variant identification from pools of eight synthetic DNA and RNA samples corresponding to the N1 gene, as well as from heat-inactivated SARS-CoV-2 virus. Single round pooled testing of barcoded samples with SAMPA can be a valuable tool for rapid and scalable population testing of infectious disease.

Comparative transcriptomic analysis of mammary gland tissues reveals the critical role of GPR110 in palmitic acid-stimulated milk protein and fat synthesis.

The G protein-coupled receptors (GPCR) sensing nutritional signals (amino acids, fatty acids, glucose, etc.) are not fully understood. In this research, we used transcriptome sequencing to analyse differentially expressed genes (DEG) in mouse mammary gland tissues at puberty, lactation and involution stages, in which eight GPCR were selected out and verified by qRT-PCR assay. It was further identified the role of GPR110-mediating nutrients including palmitic acid (PA) and methionine (Met) to improve milk synthesis using mouse mammary epithelial cell line HC11. PA but not Met affected GPR110 expression in a dose-dependent manner. GPR110 knockdown decreased milk protein and fat synthesis and cell proliferation and blocked the stimulation of PA on mechanistic target of rapamycin (mTOR) phosphorylation and sterol-regulatory element binding protein 1c (SREBP-1c) expression. In summary, these experimental results disclose DEG related to lactation and reveal that GPR110 mediates PA to activate the mTOR and SREBP-1c pathways to promote milk protein and fat synthesis.

Double J stent combined with pyelostomy tube in pediatric laparoscopic pyeloplasty: a 5-year clinical experience in a single center.

OBJECTIVE: To compare the outcome of using a double J (DJ) stent combined with pyelostomy tube with a DJ stent alone in laparoscopic pyeloplasty (LP) for pediatric ureteropelvic junction obstruction (UPJO). METHODS: A retrospective review of all patients with UPJO treated with LP between January 2017 and November 2021 was conducted in our center. According to different postoperative drainage methods patients were divided into a DJ stent group (52 cases) and a DJ stent combined with pyelostomy tube group (combination group, 41 cases). Operative time, bleeding volume, perirenal drainage stent removal time, postoperative hospital stay, postoperative complications, and renal function recovery were compared between the two groups. Renal ultrasound and diuretic renogram (DR) were used for preoperative and postoperative follow-up. RESULTS: A total of 52 patients were in the DJ stent group and 41 patients in the combination group. The mean hospital stay was 6.46 ± 2.66 days in the DJ stent group and 5.22 ± 1.63 days in the combination group (p < 0.05). Postoperative complications developed in 14 out of 52 patients in the DJ stent group (26.9%), while complications developed in 8 out of 41 patients in the combination group (19.5%) (p > 0.05). Non-catheter-related complications developed in 10/52 patients in the DJ stent group (19.2%) and only 1/41 patients in the combination group (2.4%) (p < 0.05). The renal function and renal cortex thickness in both groups were improved. CONCLUSION: Both the DJ stent drainage and the DJ stent combined with pyelostomy drainage are safe and effective. We should fully consider the patient's preoperative and intraoperative conditions and choose appropriate drainage methods. A DJ stent combined with pyelostomy tube can reduce non-catheter related complications, facilitate postoperative recovery, and the hospital stay was significantly shorter than the DJ stent group. However, it is necessary to pay attention to the nursing treatment of the pyelostomy tube and guard against the occurrence of pyelostomy tube shedding.

Effect of pneumovesicoscopic cohen surgery with adjustable suspension technique through the urethra on the treatment of primary vesicoureteral reflux disease in infants.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of pneumovesicoscopic Cohen surgery with an adjustable suspension technique through the urethra for the treatment of primary vesicoureteral reflux disease in infants. METHODS: This study retrospectively analysed the clinical data of 31 infants who underwent pneumovesicoscopic Cohen surgery with an adjustable suspension technique through the urethra in our hospital from January 2019 to December 2020. We also collected the clinical data of 29 infants who underwent open Cohen surgery in our hospital from January 2015 to December 2018 as a control variable. The clinical efficacy of the two groups was compared. RESULT: All pneumovesicoscopic Cohen surgeries were successfully completed and no patients were converted to open surgery. The amount of bleeding, duration of postoperative analgesia, duration of postoperative haematuria, incision size and length of hospital stay in the pneumovesicoscopic surgery group were significantly lower than those in the open surgery group (P < 0.05). The operation time of the pneumovesicoscopic surgery group was significantly longer than that of the open surgery group (P < 0.05). Both groups were followed for six months after surgery. At the 6-month follow-up time, there were no significant differences in the degree of hydronephrosis, renal scarring, renal atrophy, glomerular filtration rate, or KIM-1 and MCP-1 expression between the two groups (P > 0.05). CONCLUSION: Pneumovesicoscopic Cohen surgery with an adjustable suspension technique through the urethra for the treatment of primary vesicoureteral reflux disease in infants was safe and effective. This procedure had the advantages of less trauma, quick recovery and good cosmetic effects.

Single-Cell Transcriptional Landscape Reveals the Regulatory Network and Its Heterogeneity of Renal Mitochondrial Damages in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is one of the common chronic microvascular complications of diabetes in which mitochondrial disorder plays an important role in its pathogenesis. The current study delved into the single-cell level transcriptome heterogeneity of mitochondrial homeostasis in db/db mice, an animal model for study of type 2 diabetes and DKD, with single-cell RNA sequencing (scRNA-Seq) and bulk RNA-seq analyses. From the comprehensive dataset comprising 13 meticulously captured and authenticated renal cell types, an unsupervised cluster analysis of mitochondria-related genes within the descending loop of Henle, collecting duct principal cell, endothelial, B cells and macrophage, showed that they had two types of cell subsets, i.e., health-dominant and DKD-dominant clusters. Pseudotime analysis, cell communication and transcription factors forecast resulted in identification of the hub differentially expressed genes between these two clusters and unveiled that the hierarchical regulatory network of receptor-TF-target genes was triggered by mitochondrial degeneration. Furthermore, the collecting duct principal cells were found to be regulated by the decline of Fzd7, which contributed to the impaired cellular proliferation and development, apoptosis and inactive cell cycle, as well as diminished capacity for material transport. Thereby, both scRNA-Seq and bulk RNA-Seq data from the current study elucidate the heterogeneity of mitochondrial disorders among distinct cell types, particularly in the collecting duct principal cells and B cells during the DKD progression and drug administration, which provide novel insights for better understanding the pathogenesis of DKD.

Controlled Rehydration of Dried Reagents for Robust Multiplex Digital PCR.

Digital polymerase chain reaction (dPCR) is emerging as a powerful method for nucleic acid detection due to its unprecedented sensitivity and precision. However, most current dPCR platforms are inherently limited by their low multiplexing ability due to primer-pair cross interactions and spectral overlap of available fluorophores. Here, we present a novel and robust method for multiplexing dPCR that is free from primer dimerization and fluorescence channel number limitation, enabling highly precise and multiplexed detection of nucleic acid targets. By prestoring target-specific primers and probes in different storage chambers, the method physically separates reactions and thus avoids the primer-pair cross interactions and spectral overlap of different fluorescent probes that usually occur within a single-tube reaction. Furthermore, a dissolvable delay valve (DDV) is embedded between each pair of the reagent prestorage chamber and reaction microwell array. Such a DDV configuration allows full reconstitution of the prestored reagents and then generates a uniform concentration distribution of the reconstituted reagents across the entire reaction microwell array, which is favorable for achieving reliable and robust multiplex dPCR assays. We demonstrated the feasibility of this method by performing an eight-plex dPCR assay targeting the seven most common point mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and a reference sequence (wild-type KRAS allele).

miR-24-3p obstructs the proliferation and migration of human skin fibroblasts after thermal injury by targeting PPAR-ß and positively regulated by NF-κB.

Thermal injury repair is a complex process during which the maintenance of the proliferation and migration of human skin fibroblasts (HSFs) exert a crucial role. MicroRNAs have been proven to exert an essential function in repairing skin burns. This study delves into the regulatory effects of miR-24-3p on the migration and proliferation of HSFs that have sustained a thermal injury, thereby, providing deeper insight into thermal injury repair pathogenesis. The PPAR-ß protein expression level progressively increased in a time-dependent manner on the 12th, 24th and 48th hour following the thermal injury of the HSFs. The knockdown of PPAR-ß markedly suppressed the proliferation of and migration of HSF. Following thermal injury, the knockdown also promoted the inflammatory cytokine IL-6, TNF-α, PTGS-2 and P65 expression. PPAR-ß contrastingly exhibited an opposite trend. A targeted relationship between PPAR-ß and miR-24-3p was predicted and verified. miR-24-3p inhibited thermal injured HSF proliferation and migration and facilitated inflammatory cytokine expression through the regulation of PPAR-ß. p65 directly targeted the transcriptional precursor of miR-24 and promoted miR-24 expression. A negative correlation between miR-24-3p expression level and PPAR-ß expression level in rats' burnt dermal tissues was observed. Our findings reveal that miR-24-3p is conducive to rehabilitating the denatured dermis, which may be beneficial in providing effective therapy of skin burns.

Porous polyvinyl alcohol/graphene oxide composite film for strain sensing and energy-storage applications.

In this study, a flexible porous polyvinyl alcohol (PVA)/graphene oxide (GO) composite film was developed and tested for flexible strain sensing and energy-storage applications. Morphology and mechanical properties were studied; tensile strength and Young's modulus increased by 225% and 86.88%, respectively, at 0.5 wt% GO. The PVA/GO film possesses exceptional sensing ability to various mechanical strains, such as tension, compression, bending, and torsion. For example, the gauge factor of the PVA/GO film as a tensile-strain sensor was measured as 2.46 (246%). Under compression loads, the PVA/GO composite film showed piezoresistive and capacitive strain-sensing characteristics. Under 5 kPa of compression load, the relative resistance increased by 81% with a 100 msec response time; the relative capacitance increased by 160% with a 120 msec response time. The PVA/GO strain sensor exhibited high durability and reliability over 20 × 103cycles of tensile strain and bending at 3.33 Hz. Moreover, the PVA/GO composite film showed good electrochemical properties due to its porous structure; the maximum capacitance was 124.7 F g-1at 0.5 wt% GO. After 20 × 103charging-discharging cycles, the capacitance retention rate was 94.45%, representing high stable capacitance performance. The results show that electrically conductive porous PVA nanocomposite films are promising candidates for strain sensing and energy-storage devices.

Single-site laparoscopic high ligation of the extraperitoneal hernia sac with an epidural needle for incarcerated ovarian hernia in infants.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of single-site laparoscopic extraperitoneal hernia sac ligation with an epidural needle for incarcerated ovarian hernias in infants and young children. METHODS: The clinical data of 38 infants with incarcerated ovarian hernias who underwent single-site laparoscopic extradural needle extraperitoneal hernia sac ligation from January 2015 to January 2018 were retrospectively analysed. RESULTS: All procedures were successfully performed using laparoscopy with no need for conversion to open surgery. The time of hospital stay was 1.30 ± 0.39 days. During hospitalization and follow-up, there were no complications, such as intestinal or bladder injury, abdominal wall vascular injury, ovarian atrophy, hernia recurrence or contralateral indirect hernia. However, three patients experienced complications, including two cases of poor healing of the umbilical incision and one case of suture granuloma. CONCLUSIONS: Single-site laparoscopic high ligation of the extraperitoneal hernia sac with an epidural needle is a safe and feasible method for the treatment of incarcerated ovarian hernias in infants and young children. It has the advantages of minimal trauma, no scarring and good cosmetic effects.

Polycrystalline Few-Layer Graphene as a Durable Anticorrosion Film for Copper.

Corrosion of metals in atmospheric environments is a worldwide problem in industry and daily life. Traditional anticorrosion methods including sacrificial anodes or protective coatings have performance limitations. Here, we report atomically thin, polycrystalline few-layer graphene (FLG) grown by chemical vapor deposition as a long-term protective coating film for copper (Cu). A six-year old, FLG-protected Cu is visually shiny and detailed material characterizations capture no sign of oxidation. The success of the durable anticorrosion film depends on the misalignment of grain boundaries between adjacent graphene layers. Theoretical calculations further found that corrosive molecules always encounter extremely high energy barrier when diffusing through the FLG layers. Therefore, the FLG is able to prevent the corrosive molecules from reaching the underlying Cu surface. This work highlights the interesting structures of polycrystalline FLG and sheds insight into the atomically thin coatings for various applications.

Thermo-Responsive ZnPc-g-TiO2-g-PNIPAM Photocatalysts Sensitized with Phthalocyanines for Water Purification under Visible Light.

A novel thermo-responsive 2,9(10),16(17),23(24)-tetrakis[(3-carboxyacrylamide) phthalocyaninato] zinc (ZnPc)-g-TiO2-g-poly(N-isopropylacrylamide) (PNIPAM) photocatalyst modified with phthalocyanines was prepared. The photocatalyst exhibited thermo-responsive properties due to the introduction of PNIPAM, which performed recovery for reuse above the lower critical solution temperature (LCST, about 26 °C). ZnPc-g-TiO2-g-PNIPAM effectively expanded the light response range to the visible light region and inhibited the recombination of electron-hole pairs, which enhanced the performance of the photocatalyst. As expected, ZnPc-g-TiO2-g-PNIPAM (0.3 g/L) exhibited excellent photocatalytic performance for the removal of Rhodamine B (RhB, 1.0 × 10-5 mol/L) and methylene blue (MB, 1.0 × 10-5 mol/L) under visible light, which reached 97.2% and 88.6% at 20 °C within 40 min, respectively. Furthermore, the influence of temperature upon photocatalytic performance was also investigated. When the temperature increased from 20 °C to 45 °C, the removal of RhB decreased by approximately 53.8%. The stability of the photocatalyst demonstrated that the photocatalytic activity was still above 80% for the removal of RhB after 3 cycles. Above all, this work provided an intelligent thermally responsive photocatalyst based on phthalocyanine for water purification under visible light.

Ultrasound-Guided Continuous Thoracic Paravertebral Block Improves Patient's Quality of Recovery After Open Hepatectomy: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.

Surgical strategy of lumbopelvic instrumentation in the treatment of lumbosacral tuberculosis: S2-alar-iliac screws vs iliac screws.

The objective of this study was to evaluate the feasibility and clinical outcomes of S2-alar-iliac (S2AI) and iliac screw (IS) techniques in the lumbopelvic reconstruction of lumbosacral tuberculosis patients. From January 2014 to August 2016, 26 patients with lumbosacral tuberculosis attending the 8th Medical Centre of Chinese PLA General Hospital were included in this retrospective study. The subjects were divided into two groups based on the lumbopelvic fixation type (16 patients in the S2AI group, 10 patients in the IS group). The operation time, blood loss, length of hospitalisation, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, visual analogue scale (VAS), Oswestry Disability Index (ODI), ambulatory status, and 36-Item Short-Form Health Survey (SF-36) scores of the patients in two groups were recorded and compared. In addition, surgical complications were collected and analysed. The operation time and intraoperative blood loss were significantly lower in the S2AI group than that in the IS group (P < .05). Compared with preoperative data, postoperative data showed significant improvement in ESR, CRP level, ODI scores, VAS scores, ambulatory status, and SF-36 (P < .05), but there was no significant difference in remission degree between the two groups. Compared with IS group, The S2AI group had significantly lower rates of symptomatic screw prominence (P < .05). Both the IS and S2AI fixation techniques can achieve satisfactory outcomes for the restoration of lumbosacral stability of lumbosacral tuberculosis. Furthermore, compared to the traditional IS fixation technique, the S2AI fixation technique can shorten operation time and reduce surgical trauma for the treatment of lumbosacral tuberculosis.

Mini-laparoscopic pyeloplasty to treat UPJO in infants.

PURPOSE: The aim of this study was to investigate the safety and clinical efficacy of mini-laparoscopic pyeloplasty in treating ureteropelvic junction obstruction (UPJO) in infants. MATERIAL AND METHODS: We retrospectively analysed the clinical data of 66 infants with UPJO from January 2013 to August 2018 at our hospital. They were divided into the laparoscopic surgery group (group A) and the open surgery group (group B), depending on the surgical method. RESULTS: The bleeding volume, analgesia duration, postoperative hospitalization duration, and incision length in group A were significantly less than those in group B (p < .05). The incidence of incision dehiscence was 0% in group A and 11.7% in group B (p = .045). At the postoperative follow-up, the incidence of anastomotic stenosis was 6.2% in group A and 5.9% in group B (p = .719). The anteroposterior diameter and glomerular filtration rate were significantly improved at the one-year follow-up, but there was no significant difference between the groups (p > .05). CONCLUSIONS: Mini-laparoscopic pyeloplasty to treat UPJO in infants has the same early clinical efficacy and safety as open surgery, and this procedure has the advantages of fewer incisions, less pain, quicker recovery, and better cosmetic outcomes.

Herkinorin negatively regulates NLRP3 inflammasome to alleviate neuronal ischemic injury through activating Mu opioid receptor and inhibiting the NF-κB pathway.

Herkinorin is a novel opioid receptor agonist. Activation of opioid receptors, a member of G protein coupled receptors (GPCRs), may play an important role in Herkinorin neuroprotection. GPCRs may modulate NOD-like receptor protein 3 (NLRP3)-mediated inflammatory responses in the mechanisms of inflammation-associated disease and pathological processes. In this study, we investigated the effects of Herkinorin on NLRP3 and the underlying receptor and molecular mechanisms in oxygen-glucose deprivation/reperfusion (OGD/R)-treated rat cortex neurons. First, Western blot analysis showed that Herkinorin can inhibit the activation of NLRP3 and Caspase-1, decrease the expression of interleukin (IL)-1ß, and decrease the secretion of IL-6 and tumour necrosis factor α detected by enzyme-linked immunosorbent assay in OGD/R-treated neurons. Then we found that Herkinorin downregulated NLRP3 levels by inhibiting the activation of nuclear factor kappa B (NF-κB) pathway, reducing the phosphorylation level of p65 and IκBα in OGD/R-treated neurons (p < .05 or .01, n = 3 per group). Instead, both the mu opioid receptor (MOR) inhibitor, ß-funaltrexamine, and MOR knockdown reversed the effects of Herkinorin on NLRP3 (p < .05 or .01, n = 3 per group). Further, we found that the level of ß-arrestin2 decreased in the cell membrane and increased in the cytoplasm after Herkinorin pretreatment in OGD/R-treated neurons. In co-immunoprecipitation experiments, Herkinorin increased the binding of IκBα with ß-arrestin2, decreased the ubiquitination level of IκBα, and ß-arrestin2 knockdown reversed the effects of Herkinorin on IκBα in OGD/R-treated neurons (p < .05 or .01, n = 3 per group). Our data demonstrated that Herkinorin negatively regulated NLRP3 inflammasome to alleviate neuronal ischemic injury through inhibiting NF-κB pathway mediated primarily by MOR activation. Inhibition of the NF-κB pathway by Herkinorin may be achieved by decreasing the ubiquitination level of IκBα, in which ß-arrestin2 may play an important role.

M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98/DUSP1/JNK axis.

Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ-exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)-98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX-treated mice, as manifested by reduced bone mineral density and decreased number of bone trabecula. The bone loss was further aggravated by treatment with M1Mφ-Exos. Exos also suppressed osteogenic differentiation of MC3T3-E1 cells. miRNA microarray analysis revealed that the miR-98 level was notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR-98. Meanwhile, downregulation of miR-98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3-E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ-derived exosomal miR-98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR-98 may therefore serve as a therapeutic target in OP management.

Antiosteoporosis effect of geraniin on ovariectomy-induced osteoporosis in experimental rats.

Osteoporosis is a skeletal condition that is characterized by decreasing bone density and deteriorating bone mass. The plant-based phytoconstituent such as geraniin possesses better therapeutic potentials in biomedical field. In the current experimental study, we planned to scrutinize the therapeutic potential of geraniin against ovariectomy (OVX)-induced osteoporosis in rats and find the possible mechanism. Healthy Sprague Dawley rats were randomized into six groups and subjected to geraniin and alendronate (ALN) treatment for 10 weeks. Body weight, uterus, femur weight, bone biochemical, bone turnover markers, inflammatory cytokine, calcium, phosphorus, vitamin D (Vit D), urine, hormones, and antioxidant level were estimated. Geraniin significantly (p < .001) reduced the level of bone turnover markers including beta-CrossLaps (ß-CTx), ALN, osteocalcin (OC), alkaline phosphatase (ALP), and bone Gla protein (BGP); reduced the biomechanical parameters including maximum load, energy, stiffness, maximum stress, and Young's modulus; reduced the level of calcium (Ca) and phosphorus (P); and increased the level of vitamin D (Vit D) as compared with OVX-induced osteoporosis rats. Geraniin increased the level of bone structure parameters, namely bone mineral density, bone mineral content, tissue mineral density, bone volume fraction, and trabecular number; increased the level of osteoprotegerin (OPG) and OPG/RANKL; and reduced the level of receptor activator of nuclear factor kappa-Β ligand (RANKL). Geraniin significantly (p < .001) increased the level of glutathione (GSH) and reduced the level of malonaldehyde (MDA) in the liver, intestine, and bone of OVX-induced osteoporosis rats. Geraniin significantly (p < .001) decreased the level of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) pro-inflammatory cytokines. We also argue that geraniin could be an excellent candidate to treat and control bone-related disease or disorders.

Intraoperative hypotension, oliguria and operation time are associated with pulmonary embolism after radical resection of head and neck cancers: a case control study.

BACKGROUND: Postoperative pulmonary embolism (PE) is a serious thrombotic complication in the patients with otolaryngologic cancers. We investigated the risk factors associated with postoperative PE after radical resection of head and neck cancers. METHODS: A total of 3512 patients underwent head and neck cancers radical resection from 2013 to 2019. A one-to-three control group without postoperative PE was selected matched by age, gender, and type of cancer. Univariate analyses were performed for the perioperative patient data including hemodynamic management factors. Conditional logistic regression was used to analyze the factors and their odds ratios. RESULTS: Postoperative PE was prevalent in 0.85% (95%CI = 0.56-1.14). Univariate analyses showed that a high ASA grade, high BMI, and smoking history may be related to postoperative PE. There was significantly difference in operation time between the two groups, especially for> 4 h [22(78.6%) vs 43(51.2%), P = .011]. The urine output was lower [1.37(0.73-2.21) ml·kg- 1·h- 1 vs 2.14(1.32-3.46) ml·kg- 1·h- 1, P = .006] and the incidence of oliguria was significantly increased (14.3% vs 1.2%, P = .004) in the PE group. Multivariable conditional logistic regression showed postoperative PE were associated with the cumulative duration for intraoperative hypotension (OR = 2.330, 95%CI = 1.428-3.801, P = .001), oliguria (OR = 14.844, 95%CI = 1.089-202.249, P = .043), and operation time > 4 h (OR = 4.801, 95%CI = 1.054-21.866, P = .043). CONCLUSIONS: The intraoperative hypotension, oliguria, and operation time > 4 h are risk factors associated with postoperative PE after radical resection of head and neck cancers. Improving intraoperative hemodynamics management to ensure adequate blood pressure and urine output may reduce the occurrence of such complications.