Bilirubin ameliorates osteoarthritis via activating Nrf2/HO-1 pathway and suppressing NF-κB signalling.

Osteoarthritis (OA) is a chronic degenerative joint disease that affects worldwide. Oxidative stress plays a critical role in the chronic inflammation and OA progression. Scavenging overproduced reactive oxygen species (ROS) could be rational strategy for OA treatment. Bilirubin (BR) is a potent endogenous antioxidant that can scavenge various ROS and also exhibit anti-inflammatory effects. However, whether BR could exert protection on chondrocytes for OA treatment has not yet been elucidated. Here, chondrocytes were exposed to hydrogen peroxide with or without BR treatment. The cell viability was assessed, and the intracellular ROS, inflammation cytokines were monitored to indicate the state of chondrocytes. In addition, BR was also tested on LPS-treated Raw264.7 cells to test the anti-inflammation property. An in vitro bimimic OA microenvironment was constructed by LPS-treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2/HO-1 pathway and suppressing NF-κB signalling. An ACLT-induced OA model was constructed to test the in vivo therapeutic efficacy of BR. Compared to the clinical used HA, BR significantly reduced cartilage degeneration and delayed OA progression. Overall, our data shows that BR has a protective effect on chondrocytes and can delay OA progression caused by oxidative stress.

SPACA6P-AS: a trailblazer in breast cancer pathobiology and therapeutics.

OBJECTIVE: The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on its expression pattern, association with clinical-pathological features, impact on prognosis, as well as its molecular and immunological implications. METHODS: Bioinformatics analysis was conducted utilizing RNA sequencing data of 1083 BC patients from the TCGA database. Functional exploration of SPACA6P-AS was carried out through the construction of survival curves, GO and KEGG enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA). Furthermore, its functionality was validated through in vitro cell experiments and in vivo nude mouse model experiments. RESULTS: SPACA6P-AS showed a remarkable increase in expression levels in BC tissues (p < 0.001) and demonstrated a close relationship to poor prognosis (overall survival HR = 1.616, progression-free interval HR = 1.40, disease-specific survival HR = 1.54). Enrichment analysis revealed that SPACA6P-AS could impact biological functions such as protease regulation, endopeptidase inhibitor activity, taste receptor activity, taste transduction, and maturity-onset diabetes of the young pathway. ssGSEA analysis indicated a negative correlation between SPACA6P-AS expression and immune cell infiltration like dendritic cells and neutrophils, while a positive correlation was observed with central memory T cells and T helper 2 cells. Results from in vitro and in vivo experiments illustrated that silencing SPACA6P-AS significantly inhibited the proliferation, migration, and invasion capabilities of BC cells. In vitro experiments also highlighted that dendritic cells with silenced SPACA6P-AS exhibited enhanced capabilities in promoting the proliferation of autologous CD3 + T cells and cytokine secretion. These discoveries elucidate the potential multifaceted roles of SPACA6P-AS in BC, including its potential involvement in modulating immune cell infiltration in the tumor microenvironment. CONCLUSION: The high expression of lncRNA SPACA6P-AS in BC is closely linked to poor prognosis and may facilitate tumor progression by influencing specific biological processes, signaling pathways, and the immune microenvironment. The regulatory role of SPACA6P-AS positions it as a prospective biomarker and target for therapeutic approaches for BC diagnosis and intervention.

Comparison of three frailty scales for prediction of prolonged postoperative ileus following major abdominal surgery in elderly patients: a prospective cohort study.

BACKGROUND: To determine whether frailty can predict prolonged postoperative ileus (PPOI) in older abdominal surgical patients; and to compare predictive ability of the FRAIL scale, the five-point modified frailty index (mFI-5) and Groningen Frailty Indicator (GFI) for PPOI. METHODS: Patients (aged ≥ 65 years) undergoing major abdominal surgery at our institution between April 2022 to January 2023 were prospectively enrolled. Frailty was evaluated with FRAIL, mFI-5 and GFI before operation. Data on demographics, comorbidities, perioperative management, postoperative recovery of bowel function and PPOI occurrence were collected. RESULTS: The incidence of frailty assessed with FRAIL, mFI-5 and GFI was 18.2%, 38.4% and 32.5% in a total of 203 patients, respectively. Ninety-five (46.8%) patients experienced PPOI. Time to first soft diet intake was longer in patients with frailty assessed by the three scales than that in patients without frailty. Frailty diagnosed by mFI-5 [Odds ratio (OR) 3.230, 95% confidence interval (CI) 1.572-6.638, P = 0.001] or GFI (OR 2.627, 95% CI 1.307-5.281, P = 0.007) was related to a higher risk of PPOI. Both mFI-5 [Area under curve (AUC) 0.653, 95% CI 0.577-0.730] and GFI (OR 2.627, 95% CI 1.307-5.281, P = 0.007) had insufficient accuracy for the prediction of PPOI in patients undergoing major abdominal surgery. CONCLUSIONS: Elderly patients diagnosed as frail on the mFI-5 or GFI are at an increased risk of PPOI after major abdominal surgery. However, neither mFI-5 nor GFI can accurately identify individuals who will develop PPOI. TRIAL REGISTRATION: This study was registered in Chinese Clinical Trial Registry (No. ChiCTR2200058178). The date of first registration, 31/03/2022, https://www.chictr.org.cn/ .

Serum levels of n-3 PUFA and colorectal cancer risk in Chinese population.

Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case­control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.

A prospective study of chronic postsurgical pain in elderly patients: incidence, characteristics and risk factors.

BACKGROUND: Due to the continued growth of surgical procedures in older adults and the significant impact of chronic postsurgical pain (CPSP), it is crucial to improve our understanding of the occurrence of CPSP as well as the appropriate prevention and treatment. We therefore conducted this study to determine the incidence, characteristics and risk factors of CPSP in elderly patients at both 3 and 6 months after surgery. METHODS: Elderly patients (aged ≥ 60 years) undergoing elective surgery in our institution between April 2018 and March 2020 were prospectively enrolled in this study. Data on demographics, preoperative psychological well-being, intraoperative surgical and anesthesia management, and acute postoperative pain intensity were collected. At 3 and 6 months after surgery, patients received telephone interview and completed the questionnaires regarding chronic pain characteristics, analgesic consumption, and interference of the pain with activities of daily living (ADL). RESULTS: A total of 1065 elderly patients were followed up for 6 postoperative months and included in final analysis. At 3 and 6 months after operation, the incidence of CPSP was 35.6% [95% confidence interval (95% CI) 32.7 - 38.8%] and 21.5% (95% CI 19.0% - 23.9%), respectively. CPSP cause negative impacts on patient's ADL and most particularly on mood. Neuropathic features were found in 45.1% of the patients with CPSP at 3 months. At 6 months, 31.0% of those with CPSP reported that the pain had neuropathic features. Preoperative anxiety [3 months: Odds ratio (OR) 2.244, 95% CI 1.693 to 2.973; 6 months: OR 2.397, 95% CI 1.745 to 3.294], preoperative depression (3 months: OR 1.709, 95% CI 1.292 to 2.261; 6 months: OR 1.565, 95% CI 1.136-2.156), orthopedic surgery (3 months: OR 1.927, 95% CI 1.112 to 3.341; 6 months: OR 2.484, 95% CI 1.220 to 5.061), higher pain severity on movement within postoperative 24 h (3 months: OR 1.317, 95% CI 1.191 to 1.457; 6 months: OR 1.317, 95% CI 1.177 to 1.475) were associated with a higher risk for CPSP independently at both 3 and 6 months after surgery. CONCLUSIONS: CPSP is a common postoperative complication in elderly surgical patients. Preoperative anxiety and depression, orthopedic surgery, and greater intensity of acute postoperative pain on movement are associated with an increased risk for CPSP. It should be kept in mind that developing psychological interventions to reduce anxiety and depression and optimizing the management of acute postoperative pain will be effective in reducing the development of CPSP in this population.

Cost-effectiveness analysis of cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplant recipients from a US payer perspective.

To evaluate the cost-effectiveness of letermovir versus no prophylaxis for the prevention of cytomegalovirus infection and disease in adult cytomegalovirus-seropositive allogeneic hematopoietic cell transplantation (allo-HCT) recipients. A decision model for 100 patients was developed to estimate the probabilities of cytomegalovirus infection, cytomegalovirus disease, various other complications, and death in patients receiving letermovir versus no prophylaxis. The probabilities of clinical outcomes were based on the pivotal phase 3 trial of letermovir use for cytomegalovirus prophylaxis versus placebo in adult cytomegalovirus-seropositive recipients of an allo-HCT. Costs of prophylaxis with letermovir and of each clinical outcome were derived from published sources or the trial clinical study reports. Incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life year (QALY) gained were used in the model. One-way and probabilistic sensitivity analyses were conducted to explore uncertainty around the base-case analysis. In this model, the use of letermovir prophylaxis would lead to an increase of QALYs (619) and direct medical cost ($1 733 794) compared with no prophylaxis (578 QALYs; $710 300) in cytomegalovirus-seropositive recipients of an allo-HCT. Letermovir use for cytomegalovirus prophylaxis was a cost-effective option versus no prophylaxis with base-case analysis ICER $25 046/QALY gained. One-way sensitivity analysis showed the most influential parameter was mortality rate. The probabilistic sensitivity analysis showed a 92% probability of letermovir producing an ICER below the commonly accepted willingness-to-pay threshold of $100 000/QALY gained. Based on this model, letermovir use for cytomegalovirus prophylaxis was a cost-effective option in adult cytomegalovirus-seropositive recipients of an allo-HCT.

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

Background: Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. Methods: A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. Results: The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Conclusions: Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI.

6-Shogaol reduces progression of experimental endometriosis in vivo and in vitro via regulation of VGEF and inhibition of COX-2 and PGE2-mediated inflammatory responses.

Endometriosis (EM) is one of the most common gynaecological disorder affecting women in their reproductive age. Mechanisms involved in the pathogenesis of EM remains poorly understood, however inflammatory responses have been reported to be significantly involved. The efficacy of 6-shogaol on proliferation of endometriotic lesions and inflammatory pathways in experimentally-induced EM model was explored in this study. EM was stimulated in Sprague-Dawley rats by implantation of autologous endometrium onto the peritoneum abdominal wall. Separate groups were treated with 6-shogaol (50, 100 or 150 mg/kg b.wt/day) via oral gavage for one month period. Gestrinone (GTN) group received GTN (0.5 mg/kg/day) as positive control. Five weeks after implantation, the spherical volume of ecto-uterine tissues was determined. Treatment with 6-shogaol significantly reduced the implant size. Histological analysis reported atrophy and regression of the lesions. 6-shogaol administration effectively down-regulated NF-κB signaling, VEGF and VEGFR-2 (Flk-1) expression in the endometriotic lesions. Excess production of IL-1ß and IL-6 (pro-inflammatory cytokines), PGE2 and nitric oxide (NO) were reduced. Overall, the results of the study reveal the efficacy of 6-shogaol against endometriosis via effectively suppressing proliferation of the lesions and modulating angiogenesis and COX-2/NF-κB-mediated inflammatory cascades.

Inhibition of long non-coding RNA ROR reverses resistance to Tamoxifen by inducing autophagy in breast cancer.

This study explored the mechanism underlying long non-coding RNA ROR regulating autophagy on Tamoxifen resistance in breast cancer. Cancer tissues and adjacent normal tissues were collected from 74 breast cancer patients. Human breast cancer BT474 cells were assigned into blank, phosphate buffered saline, Tamoxifen, negative control + Tamoxifen, siROR + Tamoxifen, 3-methyladenine + Tamoxifen, and siROR + 3-methyladenine + TA groups. The expression of long non-coding RNA ROR and expressions of multi-drug resistance-associated P-glycoprotein and glutathione S-transferase-π messenger RNA were detected using quantitative real-time polymerase chain reaction. The expressions of light chain 3, Beclin 1, multi-drug resistance-associated P-glycoprotein, and glutathione S-transferase-π protein were determined using western blotting. Cell proliferation, invasion, and migration abilities were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Transwell assay, and scratch test, respectively. The long non-coding RNA ROR expression was higher in the breast cancer tissues than that in the adjacent normal tissues. Compared with the blank group, light chain 3 and Beclin 1 expressions were increased in the siROR + Tamoxifen group but decreased in the 3-methyladenine + Tamoxifen group; these data indicated that downregulated long non-coding RNA ROR promoted autophagy. In comparison with the blank group, multi-drug resistance-associated P-glycoprotein and glutathione S-transferase-π messenger RNA and protein expressions were reduced in the siROR + Tamoxifen group but elevated in the 3-methyladenine + Tamoxifen group, suggesting that downregulated long non-coding RNA ROR suppressed the drug resistance to Tamoxifen and the inhibition of autophagy reversed the effect of long non-coding RNA ROR on drug resistance. Compared with the Tamoxifen, negative control, and siROR + 3-methyladenine + Tamoxifen groups, the cell proliferation, invasion, and migration in the siROR + Tamoxifen group were much decreased; these results implied that downregulated long non-coding RNA ROR suppressed BT474 cell proliferation, invasion, and migration and reversed the effect of Tamoxifen on the BT474 cells. These results indicate that inhibition of long non-coding RNA ROR reverses resistance to Tamoxifen by inducing autophagy in breast cancer.

Systematic review of cost-effectiveness analyses for combinations of prevention strategies against human papillomavirus (HPV) infection: a general trend.

BACKGROUND: Due to the arrival of multi-valent HPV vaccines, it is more and more important to have a better understanding of the relationship between vaccination and screening programmes. This review aimed to: (1) collect published evidence on the cost-effectiveness profile of different HPV prevention strategies and, in particular, those combining vaccination with changes in screening practices; (2) explore the cost-effectiveness of alternative preventive strategies based on screening and vaccination. METHODS: A systematic literature review was conducted in order to identify the relevant studies regarding the cost-effectiveness of prevention strategies against HPV infection. Analysis comparing the modelling approaches between studies was made along with an assessment of the magnitude of impact of several factors on the cost-effectiveness of different screening strategies. RESULTS: A total of 18 papers were quantitatively summarised within the narrative. A high degree of heterogeneity was found in terms of how HPV prevention strategies have been assessed in terms of their economic and epidemiological impact, with variation in screening practice and valence of HPV vaccination found to have large implications in terms of cost-effectiveness. CONCLUSIONS: This review demonstrated synergies between screening and vaccination. New prevention strategies involving multi-valence vaccination, HPV DNA test screening, delayed commencement and frequency of screening could be implemented in the future. Strategies implemented in the future should be chosen with care, and informed knowledge of the potential impact of all possible prevention strategies. Highlighted in this review is the difficulty in assessing multiple strategies. Appropriate modelling techniques will need to be utilised to assess the most cost-effective strategies.

The Mechanism of Mitochondria-Mediated Pathway in the Apoptosis of Platelets in Immune-Induced Bone Marrow Failure.

Excessive platelet apoptosis is one of the pathogenic causes of immune-induced bone marrow failure (BMF). The aim of the present study was to explore the role of mitochondria-mediated pathway in the apoptosis of platelets in immune-induced BMF. An immune-induced BMF model was established in mice, which were randomly divided into three groups: normal control (CTL) group, BMF group and cyclosporine (CSA) group (n = 10 in each group). Mice were given 0.027 g/kg CSA daily in the CSA group. Platelet count (PLT), mitochondrial transmembrane potential (ΔΨm), cytochrome C (CytC), phosphatidylserine (PS), calcium ion (Ca²âº) and expression of proteins of the mitochondrial apoptotic pathway, including Bak, Bax, caspase-3, caspase-8 and caspase-9, was examined and compared. Compared with the CTL group, the BMF group had significantly a lower level of PLC and ΔΨm, but higher levels of CytC, PS, Ca²âº and higher expression levels of Bak, Bax, cleaved caspase-9 and cleaved caspase-3 (P < 0.05). CSA restored the above changes in the BMF model (P < 0.05). Further studies showed that intravenous injection of the caspase-9 inhibitor Z-LE(OMe)HD(OMe)-fluoromethylketone (FMK) into the mice could significantly inhibit apoptosis of the platelets and the effect of CSA treatment when compared to the BMF group, and exerted a better protective effect from apoptosis if the caspase-9 inhibitor was combined with the CSA treatment. These results revealed that platelet apoptosis may play an important role in the reduction of platelet of immune-induced BMF probably through the mitochondrial pathway.

[Serum level of vitamin A in children with pneumonia aged less than 3 years].

OBJECTIVE: To investigate the association of the serum level of vitamin A (VA) with the severity of pneumonia and recurrent respiratory infection (RRI) within one year after treatment in children with pneumonia, and to provide a basis for serum VA level used as an index for judgment of the condition of pneumonia and prediction of the risk of recurrent respiratory infection. METHODS: A total of 88 children with pneumonia aged less than 3 years were enrolled as study subjects. Serum VA level was measured on admission, and the development of RRI was followed up by telephone within 1 year after discharge. RESULTS: The children with pneumonia showed a reduction in the serum level of VA (0.8±0.3 µmol/L). The severe pneumonia group had a significantly lower serum level of VA than the mild pneumonia group (0.7±0.3 µmol/L vs 0.9±0.3 µmol/L; P<0.05), as well as a significantly higher detection rate of vitamin A deficiency (VAD) than the mild pneumonia group (63% vs 28%; P<0.05). The children were followed up for 1 year. The VAD-pneumonia group showed a significantly higher incidence of RRI than the normal VA-pneumonia group (49% vs 18%; P<0.05), while there were no significant differences in the incidence of RRI between the suspected subclinical vitamin A deficiency (SSVAD)-pneumonia group and the normal VA-pneumonia group, as well as between the VAD-pneumonia group and the SSVAD-pneumonia group (P>0.05). CONCLUSIONS: Children with pneumonia often have a low level of VA, and the level of VA is associated with the severity of pneumonia and the development of RRI afterwards.

Molecular Mechanism of Salvia miltiorrhiza in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking Technology.

Purpose: This study aimed to investigate the effect of Salvia miltiorrhiza on colorectal cancer, as well as the mechanisms involved. Methods: The active compounds of Salvia miltiorrhiza and the associated genes in colorectal cancer were sourced from publicly available databases. Targets associated with colorectal cancer were identified by searching the GeneCards and OMIM databases. Subsequently, the Cytoscape 3.6.0 software was employed to create a regulatory network that illustrates the relationships among active ingredients, colorectal cancer, and their corresponding targets. The String database was utilized to generate a PPI network. Molecular docking studies, conducted with AutoDock Vina, verified the binding capabilities of these active components to core targets. The findings from network pharmacology analysis were corroborated through in vitro experiments. Results: In this study, we identified 39 active components derived from Salvia miltiorrhiza that are predicted to target 544 genes associated with colorectal cancer through network pharmacology. Through a combined analysis of network pharmacology, we isolated three key targets: SRC, IL6, and INS. Molecular docking results convincingly demonstrated Salvia miltiorrhiza's strong binding affinity to these targets. Additionally, in vitro experiments confirmed that Salvia miltiorrhiza effectively inhibited the progression of colorectal cancer via regulating the INS/SRC/IL6 pathway. Conclusion: Salvia miltiorrhiza emerges as a compelling herbal intervention for colorectal cancer. This study lays the foundation for potential future clinical trials assessing the efficacy of Salvia miltiorrhiza in the management of colorectal cancer.

Exploration of the Molecular Mechanism of Curcuma aromatica Salisb's Anticolorectal Cancer Activity via the Integrative Approach of Network Pharmacology and Experimental Validation.

Curcuma aromatica Salisb (Cur), a well-known herbal medicine, has a wide spectrum of anti-inflammatory, anticarcinogenic, and antioxidant activities. However, the roles of its active compounds and potential mechanisms in colorectal cancer remain unknown. This research utilized network pharmacology and experimental validation to explore the possible mechanisms by which Cur protects against colorectal cancer. The active compounds of Cur and related genes for colorectal cancer were obtained from public databases. The DrugBank database was used to search for anticolorectal cancer drugs licensed through the FDA and their targets, and a "drug-component-target" relationship network was created using the Cytoscape program. The String database produced the PPI network. The ability of these active ingredients to bind to core targets was confirmed by molecular docking using AutoDock Vina. Cell and animal experiments were then carried out. A total of 274 targets were obtained from Cur, 49 of which were potential therapeutic targets. Four key targets, PTGS2, AKT1, TP53, and estrogen receptor 1 (ESR1), were screened via the PPI network and the FDA drug-target network. Molecular docking results revealed that Cur had strong binding abilities to these targets. In vivo and in vitro experiments demonstrated that Cur suppressed the development of colorectal cancer by regulating its targets (PTGS2, AKT1, TP53, and ESR1), which play crucial roles in promoting apoptosis and suppressing cell proliferation, migration, and invasion. Collectively, Cur protects against colorectal cancer by regulating the AKT1/PTGS2/ESR1 and P53 pathways, which lays the groundwork for further research and clinical applications of Cur in colorectal cancer therapy.

Postoperative complications and axial length growth after bilateral congenital cataract surgery: eyes with microphthalmos compared to a comparison group.

PURPOSE: To investigate the postoperative clinical outcomes and axial length (AL) growth of infants with congenital cataracts and microphthalmos following first-stage cataract surgery. DESIGN: Retrospective case-control study. METHODS: Setting: Single centre. Infants with congenital cataract that met the inclusion criteria were classified into two groups: the microphthalmos and comparison groups. All infants underwent a thorough ophthalmologic examination before surgery, and one week, 1 month, 3 months, and every 3 months after surgery. RESULTS: This study enrolled 21 infants (42 eyes) in the microphthalmos group and 29 infants (58 eyes) in the comparison group. More glaucoma-related adverse events were observed in the microphthalmos group (7 eyes, 16.7%) than in the comparison group (0 eyes, 0%) (p < 0.001). At each subsequent follow-up, the comparison group had a greater AL than the microphthalmos group (all p < 0.001), and AL growth was significantly higher in the comparison group than in the microphthalmos group (all p = 0.035). Visual acuity improvement in the microphthalmos group was similar to that of the comparison group. CONCLUSION: Early surgical intervention improves visual function in infants with congenital cataracts and microphthalmos although with a higher incidence of glaucoma-related adverse events. After cataract removal, the AL growth of microphthalmic eyes is slower than that of normally developed eyes.

Circ0060467 sponges miR-6805 to promote hepatocellular carcinoma progression through regulating AIFM2 and GPX4 expression.

BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.

Retrospective efficacy analysis of olaparib combined with bevacizumab in the treatment of advanced colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a highly prevalent malignancy of the digestive tract worldwide, characterized by a significant morbidity and mortality rate and subtle initial symptoms. Diarrhea, local abdominal pain, and hematochezia occur with the development of cancer, while systemic symptoms such as anemia and weight loss occur in patients with advanced CRC. Without timely interventions, the disease can have fatal consequences within a short span. The current therapeutic options for colon cancer include olaparib and bevacizumab, which are widely utilized. This study intends to evaluate the clinical efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC, hoping to provide insights into advanced CRC treatment. AIM: To investigate the retrospective efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC. METHODS: A retrospective analysis was conducted on a cohort of 82 patients with advanced colon cancer who were admitted to the First Affiliated Hospital of the University of South China between January 2018 and October 2019. Among them, 43 patients subjected to the classical FOLFOX chemotherapy regimen were selected as the control group, and 39 patients undergoing treatment with olaparib combined with bevacizumab were selected as the observation group. Subsequent to different treatment regimens, the short-term efficacy, time to progression (TTP), and incidence rate of adverse reactions between the two groups were compared. Changes in serum-related indicators [vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9), cyclooxygenase-2 (COX-2)] and tumor markers [human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199)] levels before and after treatment were compared between the two groups at the same time. RESULTS: The objective response rate was discovered to be 82.05%, and the disease control rate was 97.44% in the observation group, which were significantly higher than the respective rates of 58.14% and 83.72% in the control group (P < 0.05). The median TTP was 24 mo (95%CI: 19.987-28.005) in the control group and 37 mo (95%CI: 30.854-43.870) in the observation group. The TTP in the observation group was significantly better than that in the control group, and the difference held statistical significance (log-rank test value = 5.009, P = 0.025). Before treatment, no substantial difference was detected in serum VEGF, MMP-9, and COX-2 levels and tumor markers HE4, CA125, and CA199 levels between the two groups (P > 0.05). Following treatment with different regimens, the above indicators in the two groups were remarkably promoted (P < 0.05), VEGF, MMP-9, and COX-2 in the observation group were lower than those in the control group (P < 0.05), and HE4, CA125, and CA199 levels were also lower than those in the control group (P < 0.05). Vis-à-vis the control group, the total incidence of gastrointestinal reactions, thrombosis, bone marrow suppression, liver and kidney function injury, and other adverse reactions in the observation group was notably lowered, with the difference considered statistically significant (P < 0.05). CONCLUSION: Olaparib combined with bevacizumab in the treatment of advanced CRC demonstrates a strong clinical effect of delaying disease progression and reducing the serum levels of VEGF, MMP-9, COX-2 and tumor markers HE4, CA125 and CA199. Moreover, given its fewer adverse reactions, it can be regarded as a safe and reliable treatment option.

Association of Dietary Intake of Zinc and Selenium with Breast Cancer Risk: A Case-Control Study in Chinese Women.

As major nonenzymatic antioxidant components in the body, dietary Zinc (Zn) and Selenium (Se) may have an impact on breast cancer development. This study aimed to investigate the relationship between dietary Zn, Se intake and breast cancer risk in Chinese women. The case-control study included 1591 cases and 1622 age-frequency matched controls. Dietary intake was collected using a validated food frequency questionnaire. Dietary Zn and Se were divided into four categories: Zn/Se from plants, Zn/Se from meat, Zn/Se from red meat, and Zn/Se from white meat. Unconditional logistic regression models and restricted cubic spline analyses were performed to identify potential associations. Zn from white meat intake was linearly and inversely associated with breast cancer risk, and Se from red meat intake was linearly and positively associated with breast cancer risk, with adjusted odds ratio and 95% confidence interval of 0.76 (0.61-0.95) and 1.36 (1.04-1.77), respectively. Non-linear relationships were found between total dietary Zn, Zn from meat, Zn from red meat intake and breast cancer risk (pnon-linearity < 0.05). In conclusion, dietary Zn and Se intake were associated with breast cancer risk in Chinese women, and the optimal intake of Zn may be beneficial for breast cancer prevention.

Recombinant protein drugs-based intra articular drug delivery systems for osteoarthritis therapy.

Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease. It weakens the motor function of patients and imposes a significant economic burden on society. The current medications commonly used in clinical practice do not meet the need for the treatment of OA. Recombinant protein drugs (RPDs) can treat OA by inhibiting inflammatory pathways, regulating catabolism/anabolism, and promoting cartilage repair, thereby showing promise as disease-modifying OA drugs (DMOADs). However, the rapid clearance and short half-life of them in the articular cavity limit their clinical translation. Therefore, the reliable drug delivery systems for extending drug treatment are necessary for the further development. This review introduces RPDs with therapeutic potential for OA, and summarizes their research progress on related drug delivery systems, and make proper discussion on the certain keys for optimal development of this area.

Fe-involved nanostructures act as photothermal transduction agents in cancer photothermal therapy.

Cancer, a disease notorious for its difficult therapy regimen, has long puzzled researchers. Despite attempts to cure cancer using surgery, chemotherapy, radiotherapy, and immunotherapy, their effectiveness is limited. Recently, photothermal therapy (PTT), a rising strategy, has gained attention. PTT can increase the surrounding temperature of cancer tissues and cause damage to them. Fe is widely used in PTT nanostructures due to its strong chelating ability, good biocompatibility, and the potential to induce ferroptosis. In recent years, many nanostructures incorporating Fe3+ have been developed. In this article, we summarize PTT nanostructures containing Fe and introduce their synthesis and therapy strategy. However, PTT nanostructures containing Fe are still in their infancy, and more effort must be devoted to improving their effectiveness so that they can eventually be used in clinics.