Ginseng-derived nanoparticles alleviate inflammatory bowel disease via the TLR4/MAPK and p62/Nrf2/Keap1 pathways.

Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy.

α-Ketoglutarate alleviates osteoarthritis by inhibiting ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway.

Osteoarthritis (OA) is the most common degenerative joint disorder that causes disability in aged individuals, caused by functional and structural alterations of the knee joint. To investigate whether metabolic drivers might be harnessed to promote cartilage repair, a liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics approach was carried out to screen serum biomarkers in osteoarthritic rats. Based on the correlation analyses, α-ketoglutarate (α-KG) has been demonstrated to have antioxidant and anti-inflammatory properties in various diseases. These properties make α-KG a prime candidate for further investigation of OA. Experimental results indicate that α-KG significantly inhibited H2O2-induced cartilage cell matrix degradation and apoptosis, reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione (GSH)/glutathione disulfide (GSSG) levels, and upregulated the expression of ETV4, SLC7A11 and GPX4. Further mechanistic studies observed that α-KG, like Ferrostatin-1 (Fer-1), effectively alleviated Erastin-induced apoptosis and ECM degradation. α-KG and Fer-1 upregulated ETV4, SLC7A11, and GPX4 at the mRNA and protein levels, decreased ferrous ion (Fe2+) accumulation, and preserved mitochondrial membrane potential (MMP) in ATDC5 cells. In vivo, α-KG treatment inhibited ferroptosis in OA rats by activating the ETV4/SLC7A11/GPX4 pathway. Thus, these findings indicate that α-KG inhibits ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway, thereby alleviating OA. These observations suggest that α-KG exhibits potential therapeutic properties for the treatment and prevention of OA, thereby having potential clinical applications in the future.

Analysis of the prevalence, risk factors, and clinical characteristics of osteoporosis in patients with essential hypertension.

BACKGROUND: The present study investigated the prevalence of osteoporosis (OP) among patients with essential hypertension (EH) in the Changchun community and analysed the correlation between EH and OP. METHODS: The study included 425 subjects with EH and 425 age- and sex-matched healthy controls. Bone mineral density (BMD) and serum creatinine (CR) levels were measured, and the subjects' current EH and OP statuses were surveyed to analyse the correlation between EH and OP. RESULTS: The EH group exhibited lower BMD and a higher rate of having OP than the control group, and this difference was statistically significant (p < 0.05). A significant sex difference in the BMD T-score was observed among the subjects (male: - 1.19 ± 1.55, female: - 1.70 ± 1.34). In both the EH group and the control group, the rate of having OP in females was greater than that in males. However, the OP prevalence among subjects with EH varied significantly by age, body weight, fracture history, nocturnal urination frequency, depression and anxiety status, duration of hypertension, and antihypertensive medication use (p < 0.05). Two-way analysis of variance suggested an effect of the interaction between different EH statuses and bone mass conditions on the serum CR values (F = 3.584, p = 0.028, bias η2 = 0.008). CONCLUSIONS: The prevalence of OP and low BMD were significantly higher among subjects with EH than among healthy controls. Additionally, the findings indicate that age, weight, fracture history, nocturnal urination frequency, depression and anxiety, duration of hypertension and antihypertensive drug use may be correlated to having OP in EH subjects, requiring further studies. Moreover, serum CR levels in subjects with different bone mass profiles were strongly influenced by the presence or absence of EH, and the serum CR levels differed significantly with the interaction of these two factors.

Gubi Zhitong formula alleviates osteoarthritis in vitro and in vivo via regulating BNIP3L-mediated mitophagy.

BACKGROUND: Osteoarthritis (OA) is characterized by degeneration of articular cartilage, leading to joint pain and dysfunction. Gubi Zhitong formula (GBZTF), a traditional Chinese medicine formula, has been used in the clinical treatment of OA for decades, demonstrating definite efficacy. However, its mechanism of action remains unclear, hindering its further application. METHODS: The ingredients of GBZTF were analyzed and performed with liquid chromatography-mass spectrometry (LC-MS). 6 weeks old SD rats were underwent running exercise (25 m/min, 80 min, 0°) to construct OA model with cartilage wear and tear. It was estimated by Micro-CT, Gait Analysis, Histological Stain. RNA-seq technology was performed with OA Rats' cartilage, and primary chondrocytes induced by IL-1ß (mimics OA chondrocytes) were utilized to evaluated and investigated the mechanism of how GBZTF protected OA cartilage from being damaged with some functional experiments. RESULTS: A total of 1006 compounds were identified under positive and negative ion modes by LC-MS. Then, we assessed the function of GBZTF through in vitro and vivo. It was found GBZTF could significantly up-regulate OA rats' limb coordination and weight-bearing capacity, and reduce the surface and sub-chondral bone erosions of OA joints, and protect cartilage from being destroyed by inflammatory factors (iNOS, IL-6, IL-1ß, TNF- α, MMP13, ADAMTS5), and promote OA chondrocytes proliferation and increase the S phage of cell cycle. In terms of mechanism, RNA-seq analysis of cartilage tissues revealed 1,778 and 3,824 differentially expressed genes (DEGs) in model vs control group and GBZTF vs model group, respectively. The mitophagy pathway was most significantly enriched in these DEGs. Further results of subunits of OA chondrocytes confirmed that GBZTF could alleviate OA-associated inflammation and cartilage damage through modulation BCL2 interacting protein 3-like (BNIP3L)-mediated mitophagy. CONCLUSION: The therapeutic effectiveness of GBZTF on OA were first time verified in vivo and vitro through functional experiments and RNA-seq, which provides convincing evidence to support the molecular mechanisms of GBZTF as a promising therapeutic decoction for OA.

Analysis of cuproptosis-related genes in Ulcerative colitis and immunological characterization based on machine learning.

Cuproptosis is a novel form of cell death, mediated by protein lipid acylation and highly associated with mitochondrial metabolism, which is regulated in the cell. Ulcerative colitis (UC) is a chronic inflammatory bowel disease that recurs frequently, and its incidence is increasing worldwide every year. Currently, a growing number of studies have shown that cuproptosis-related genes (CRGs) play a crucial role in the development and progression of a variety of tumors. However, the regulatory role of CRGs in UC has not been fully elucidated. Firstly, we identified differentially expressed genes in UC, Likewise, CRGs expression profiles and immunological profiles were evaluated. Using 75 UC samples, we typed UC based on the expression profiles of CRGs, followed by correlative immune cell infiltration analysis. Using the weighted gene co-expression network analysis (WGCNA) methodology, the cluster's differentially expressed genes (DEGs) were produced. Then, the performances of extreme gradient boosting models (XGB), support vector machine models (SVM), random forest models (RF), and generalized linear models (GLM) were constructed and predicted. Finally, the effectiveness of the best machine learning model was evaluated using five external datasets, receiver operating characteristic curve (ROC), the area under the curve of ROC (AUC), a calibration curve, a nomogram, and a decision curve analysis (DCA). A total of 13 CRGs were identified as significantly different in UC and control samples. Two subtypes were identified in UC based on CRGs expression profiles. Immune cell infiltration analysis of subtypes showed significant differences between immune cells of different subtypes. WGCNA results showed a total of 8 modules with significant differences between subtypes, with the turquoise module being the most specific. The machine learning results showed satisfactory performance of the XGB model (AUC = 0.981). Finally, the construction of the final 5-gene-based XGB model, validated by the calibration curve, nomogram, decision curve analysis, and five external datasets (GSE11223: AUC = 0.987; GSE38713: AUC = 0.815; GSE53306: AUC = 0.946; GSE94648: AUC = 0.809; GSE87466: AUC = 0.981), also proved to predict subtypes of UC with accuracy. Our research presents a trustworthy model that can predict the likelihood of developing UC and methodically outlines the complex relationship between CRGs and UC.

Comparison of the Dinoprostone Vaginal Insert and Dinoprostone Tablet for the Induction of Labor in Primipara: A Retrospective Cohort Study.

This retrospective study aimed to compare the safety and efficacy of Prostin E2 and Propess for the induction of labor (IOL) in nulliparous women between January 2018 and October 2021. The inclusion criteria were nulliparous, singleton, >37 weeks' gestation, cephalic presentation with an unfavorable cervix (Bishop score ≤ 6), no signs of labor, and use of one form of dinoprostone (Prostin E2 or Propess) for IOL. The cesarean section (C/S) rate and induction-to-birth interval were the main outcome measures. In total, 120 women were recruited. Sixty (50%) patients received Propess and 60 (50%) received repeated doses of Prostin E2. The Prostin E2 and Propess groups had similar patient characteristics, but the Bishop score was significantly higher in the Propess group than in the Prostin E2 group; therefore, multivariate analysis was conducted, and the Bishop score was not associated with the induction-to-birth interval. The C/S rate was not significantly different between the two groups, but the Propess group achieved a shorter induction-to-birth interval, a higher rate of vaginal delivery in 24 h, and a lower number of vaginal examinations than the Prostin E2 group. Propess was effective and safe in IOL and could be an option for cervical ripening in nulliparous pregnancy.

Deer antler extract promotes tibia fracture healing in mice by activating BMP-2/SMAD4 signaling pathway.

BACKGROUND: Deer antler is a traditional Chinese medicine with the function of tonifying kidney and strengthening bone, which is often used to treat orthopedic diseases. METHODS: Eight-week-old C57BL/6 mice were used as the fixation model of open tibial fracture with intramedullary nail. The mice were treated with deer antler extract (DAE) or PBS by oral gavage once daily. The tibial fracture samples were collected and performed to the tissue analysis, including X-ray, micro-CT, histology, qRT-PCR, immunohistochemistry. MC3T3-E1 cells were used to detect the effect of deer antler extract on ability of cell proliferation and migration by CCK-8 assay and cell scratch test. RESULTS: Imaging and micro-CT showed that DAE could promote the healing of tibial fracture in mice, and histological analysis showed that DAE could promote the transformation of cartilage callus to bone callus in fracture area. The results of qRT-PCR and immunohistochemistry showed that DAE could promote intrachondral ossification in fracture zone and the mechanism of promoting fracture healing may be related to the activation of BMP-2/SMAD4 signaling pathway. In the cytological experiment of DAE, it can be found that DAE promoted the proliferation of MC3T3-E1 cells and the migration of MC3T3-E1 cells at a certain concentration, which is also related to the promotion of fracture healing by DAE. CONCLUSION: DAE can promote fracture healing by activating BMP-2/SMAD4 signaling pathway. DAE has the potential to be used in clinic as an important means of promoting fracture healing.

Transcriptional sequencing analysis reveals the potential use of deer antler for "tonifying the kidney and strengthening bone".

BACKGROUND: It is recorded in the Chinese Pharmacopoeia that deer antlers can be used to tonify the kidney and strengthen bone. Although numerous studies have demonstrated that deer antler has protective effects on the kidney and bone, its molecular mechanisms remain to be elucidated. The aim of this study was to explore the molecular mechanism underlying its effects on the bone and kidney. METHODS: Water extract of pilose antler was prepared and then filtered through a 0.45 µm Hollow Fiber Cartridge (GE Healthcare, USA). The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at - 80 °C. Rats were treated with deer antler extract (DAE) prepared in advance, and gene regulatory network in the kidney and bone was detected by RNA-Seq technique. Micro-CT was used to detect bone trabecular formation, bone mineral density (BMD) and bone volume fraction (BV/TV). RESULTS: The results demonstrate that DAE could jointly heighten renal function by maintaining renal homeostasis, combating renal fibrosis, and reducing renal inflammation by regulating ion transport. Furthermore, DAE can strengthen the bone system by stimulating osteoblast differentiation and regulating bone regeneration and the bone marrow microenvironment. Micro-CT results confirmed that DAE can promote bone trabecular formation and increase BMD and BV/TV. We also identified many genes that can regulate both the kidney and bone simultaneously, which explained the theory of "kidney governing bone" at the molecular level and provided possible strategies for further application of this theory to treat diseases. CONCLUSIONS: DAE enhances renal function, maintains renal homeostasis, positively regulates skeletal system development, and increases bone mineral density. The underlying mechanism involves improving the expression levels of functional genes involved in renal function and regulation and repair, as well as genes that positively regulate skeletal system development.

Qizhi Kebitong Formula Ameliorates Streptozocin-Induced Diabetic Osteoporosis through Regulating the PI3K/Akt/NF-κB Pathway.

Background: Diabetic osteoporosis (DOP) is a progressive osteoblast dysfunction induced by high glucose, which has negative impacts on bone homeostasis. Qizhi Kebitong formula (QKF) is a traditional Chinese medicine (TCM) formula for treating DOP. However, its role in the protection of DOP has not been clarified yet. Here, we aimed to explore the potential mechanisms of QKF on DOP development via in vivo experiment. Methods: Network pharmacology was used to detect the key targets and signaling pathways of QKF on DOP. The effects of QKF on DOP were examined by the phenotypic characteristics, micro-CT, and hematoxylin-eosin (H&E) staining. The predicted targets and pathways were validated by a streptozocin- (STZ-) induced mouse model. Subsequently, the levels of the selected genes and proteins were analyzed using qRT-PCR and Western blot. Finally, AutoDock and PyMOL were used for molecular docking. Results: In this study, 90 active compounds and 2970 related disease targets have been found through network pharmacology. And QKF could improve the microstructures of femur bone mass, reduce inflammatory cell infiltration, and downregulate the levels of TNF-α, IKBKB, IL-6, and IL-1ß. Moreover, the underlying effect of PI3K/Akt/NF-κB pathways was also recommended in the treatment. Conclusion: Altogether, our findings suggested that QKF could markedly alleviate osteoblast dysfunction by modulating the key targets and PI3K/Akt/NF-κB signaling pathway.

Iatrogenic Parasitic Myoma with Two Recurrence Times after Subsequent Myomectomy: A Rare and Complicated Case Report.

Increasing number of parasitic myoma (PM) cases due to specimen morcellation during minimally invasive surgery have been reported. The patient was a 46-year-old woman receiving laparoscopic subtotal hysterectomy due to fibroids. She was diagnosed as having PM and had two recurrences after subsequent myomectomies. To prevent recurrence, specimen-contained morcellation was performed during the myomectomies and postoperative ulipristal acetate was given, but with no effects. The interval between each recurrence decreased. Progressive lower abdominal pain and prominent vessels on the myoma were the two distinct clinical characteristics that differentiated PM from general myoma. This case study highlights the importance of specimen containment before morcellation in minimally invasive surgery and implies that the pathogenesis of PM recurrence is unknown.

Safety and efficacy of contained manual morcellation during laparoscopic or robotic gynecological surgery.

OBJECTIVE: To assess the safety and efficacy of contained manual morcellation (CMM) with a tissue pouch during minimally invasive robotic or laparoscopic surgeries. METHODS: A retrospective cohort study included women who underwent robotic or laparoendoscopic single-site surgery at a tertiary referral center between February 2014 and April 2017. The specimen was postoperatively contained, sliced into one or more long strips, and then pulled out. The surgical type, specimen containment time, containment failure rate, specimen weight, manual morcellation time, and overall CMM speed (g/min) were recorded. Surgical complications related (bowel or bladder injury, ureteral injury, vascular injuries, and tumor dissemination) or not related (delayed wound healing, infection, and hernia) to CMM were also documented. The patients were followed up for 2 years. RESULTS: A total of 165 cases were recorded, comprising 149 cases that underwent laparoscopic and 16 that underwent robotic gynecological surgeries. The average time for specimen containment and manual morcellation in CMM was 6.7 ± 5.0 and 13.2 ± 11.2 min, respectively. The mean morcellation speed was 25.1 ± 8.5 g/min. Among the specimens, those of the uterus with adenomyosis had the lowest CMM speed (21.4 ± 8.0 g/min), whereas those of the uterus with myoma had the highest speed (27.5 ± 8.9 g/min). The pouch perforation rate after CMM was 13.3% and no pouch-related complication was noted. CONCLUSION: CMM is an efficient method for specimen removal.

Laparoscopic management of tubal ectopic pregnancy.

OBJECTIVES: To study the surgical morbidity associated with laparoscopic management of tubal ectopic pregnancy compared with that of open laparotomy. METHODS: A retrospective study in an academic tertiary obstetrics and gynecology referral center was conducted from 2005 through 2007. Forty-nine patients who had pathology-confirmed tubal ectopic pregnancies were divided into 2 groups, laparoscopy (n=38) and laparotomy (n=11). The main outcome measures included operative time, blood loss, and complications. RESULTS: No significant differences existed in gestational age, beta-hCG level, history of previous surgeries, pelvic inflammatory disease, or endometriosis. The laparotomy group included more patients with a history of previous ectopic pregnancy. The length of hospital stay following laparoscopic management was significantly less than that in the laparotomy group. CONCLUSION: Laparoscopic management of ectopic pregnancy can be the most beneficial procedure with maximum safety and efficacy.

Trends of Opportunistic Salpingectomy.

BACKGROUND AND OBJECTIVES: This study analyzed the trends of opportunistic salpingectomy (OS) accompanied by hysterectomy in a 9-year follow-up period at a single institute. METHODS: This retrospective cohort study included 1184 women at Hualien Tzu Chi Hospital from 2007 to 2015 who underwent hysterectomy performed with or without OS. Parameters including patient age, operating time, surgical approach, length of hospital stay, and perioperative complications were evaluated. RESULTS: There was an increase in the number of hysterectomies with OS (from 8% to 80%; P < .001) over the study period. Minimal additional operating time was necessary for hysterectomy with OS (3.7 and 3.6 minutes in open and laparoscopic surgery, respectively). No significant differences were observed in the risks of hospital readmission or blood transfusions between women who underwent hysterectomy with OS performed with the open approach and those who underwent the procedure using the laparoscopic approach. From 2007 to 2015, the proportion of open hysterectomies decreased from 56% to 6%. CONCLUSION: The results of this 9-year follow-up study revealed that, as a cancer prevention method, OS seems to be feasible and safe, requires minimal extra time, and does not increase the morbidity or long-term sequelae.

Detection and typing of minimal human papillomavirus DNA in plasma.

OBJECTIVE: For clinical study of minute human papillomavirus (HPV) DNA such as those in plasma, a sensitive method that can detect a broad spectrum of HPV type is needed. METHOD: A nested polymerase chain reaction (PCR) method which utilized a consensus primer set nested to the widely utilized MY09/MY11 primer set was developed. The HPV genotype was determined by restriction digestion of the PCR product followed by agarose gel electrophoresis. DNA purified from cancer tissue, plasma and WBC of 17 patients of stage 1 or 2 squamous carcinoma of uterine cervix were examined. RESULTS: This method readily detects a broad spectrum of at least ten genital types of HPV with a sensitivity of one viral copy. HPV DNA was detectable in all cervical cancer tissues and in 11 (65%) of the corresponding plasma, from which the genotype was successfully determined in 9 cases, all identical to that of primary cancer tissue. CONCLUSION: The high sensitivity and accuracy of this method has allowed detection of HPV in specimens of minimal viral load, such as in plasma in peripheral circulation of cervical cancer patients.

High success rate and considerable adverse events of pelvic prolapse surgery with Prolift: a single center experience.

OBJECTIVES: The aim of this study was to analyze short-term outcomes of pelvic prolapse surgery using Prolift transvaginal mesh in a teaching hospital. MATERIALS AND METHODS: Thirty-four patients who received prolapse surgery with Prolift were followed up for 7-26 months. Assessment included pre- and postoperative Pelvic Organ Prolapse Quantification (POP-Q) stage, and Urogenital Distress Inventory (UDI)-6, and Incontinence Impact Questionnaire (IIQ)-7 scores. Surgical characteristics and adverse events during follow-up were also recorded. RESULTS: Objective and subjective data were available for 29 patients. The overall anatomical success rate was 96.5 % (28/29) after a mean of 18 ± 6.3 months follow-up. The POP-Q, UDI, and IIQ all improved significantly after surgery. Uterine sparing prolapsed surgery with Prolift unexpectedly yielded a cure rate of 100%. Ten adverse events occurred during and after prolapse surgery with dyspareunia (3/34) as the most common, followed by bladder injury (2/34). CONCLUSIONS: Prolapse surgery with Prolift yielded a good anatomical outcome and satisfactory symptom improvement at different periods of follow-up, especially in uterus-sparing prolapse surgery. However, adverse events were not uncommon, and patients should be fully informed of all possible adverse events prior to surgery.

Parathyroid adenoma with hypertensive crisis and intracerebral hemorrhage mimicking hemolysis, elevated liver enzymes, low platelets syndrome.

BACKGROUND: Hyperparathyroidism is seldom encountered during pregnancy. Moreover, when the disease does occur, it is typically masked until late pregnancy or after delivery. CASE: A previously healthy multiparous woman presented with sudden-onset severe preeclampsia with hemolysis, elevated liver enzymes, low platelets syndrome at 37 weeks of gestation. Acute intracerebral hemorrhage and disseminated intravascular coagulapathy developed 24 hours after cesarean delivery and persisted after craniotomy. Hypercalcemia and hyperparathyroidism were noted, and imaging studies revealed parathyroid tumor. The patient recovered from severe preeclampsia after resection of a hemorrhagic parathyroid adenoma and was fully rehabilitated after 3 months. CONCLUSION: This patient exhibited a concealed hyperparathyroidism with acute hypertensive crisis, probably attributable to hemorrhagic parathyroid adenoma. The presentation mimics acute late-onset preeclampsia and requires vigilant diagnosis followed by surgery.