Second Affiliated Hospital of Xuzhou Medical College

The efficacy and safety of multikinase inhibitor anlotinib have been confirmed in the treatment of advanced non-small cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor lethality mediated by anlotinib were not fully elucidated, and the underlying mechanisms related to resistance remain largely elusive. Cell viability, colony formation, apoptosis and tumor growth assays were performed to examine the effect of anlotinib on lung cancer cells in vitro and in vivo. The punctate patterns of LC3-I/II were detected by confocal microscopy. HUVECs motility was detected using Transwell and scratch wound-healing assay. To visualize the microvessels, tubular formation assay was performed. The expression of LC3-I/II and beclin-1 and the changes of JAK2/STAT3/VEGFA pathway were detected by western blotting. The VEGFA levels in tumor supernatant were measured by ELISA. Anlotinib treatment decreased cell viability and induced apoptosis in Calu-1 and A549 cells. Moreover, anlotinib induced human lung cancer cell autophagy in a dose- and time-dependent manner. Blocking autophagy enhanced the cytotoxicity and anti-angiogenic ability of anlotinib as evidenced by HUVECs migration, invasion, and tubular formation assay. Co-administration of anlotinib and chloroquine (CQ) further reduced VEGFA level in the tumor supernatant, compared with that of anlotinib or CQ treatment alone. When autophagy was induced by rapamycin, the JAK2/STAT3 pathway was activated and VEGFA was elevated, which was attenuated after deactivating STAT3 by S3I-201. Further in vivo studies showed that anlotinib inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3/VEGFA pathway, and CQ enhanced this effect. Anlotinib induced apoptosis and protective autophagy in human lung cancer cell lines. Autophagy inhibition further enhanced the cytotoxic effects of anlotinib, and potentiated the anti-angiogenic property of anlotinib through JAK2/STAT3/VEGFA signaling.

PURPOSE: Microsatellites are widely distributed repetitive DNA motifs, accounting for approximately 3% of the genome. Due to mismatch repair system deficiency, insertion or deletion of repetitive units often occurs, leading to microsatellite instability. In this review, we aimed to explore the relationship between MSI and biological behaviour of colorectal carcinoma, gastric carcinoma, lymphoma/leukaemia and endometrial carcinoma, as well as the application of frameshift peptide vaccines in cancer therapy. METHODS: The relevant literature from PubMed and Baidu Xueshu were reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS: Microsatellite instability is divided into three subtypes: high-level, low-level microsatellite instability, and stable microsatellites. The majority of tumour patients with high-level microsatellite instability often show a better efficacy and prognosis than those with low-level microsatellite instability or stable microsatellites. In coding regions, especially for genes involved in tumourigenesis, microsatellite instability often results in inactivation of proteins and contributes to tumourigenesis. Moreover, the occurrence of microsatellite instability in coding regions can also cause the generation of frameshift peptides that are thought to be unknown and novel to the individual immune system. Thus, these frameshift peptides have the potential to be biomarkers to raise tumour-specific immune responses. CONCLUSION: MSI has the potential to become a key predictor for evaluating the degree of malignancy, efficacy and prognosis of tumours. Clinically, MSI patterns will provide more valuable information for clinicians to create optimal individualized treatment strategies based on frameshift peptides vaccines.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is an indicator of systemic inflammation and a prognostic marker in patients with acute coronary syndrome (ACS). This study aims to investigate the value of NLR to predict the in-hospital and long-term prognosis in patients with ST segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) by meta-analysis. METHOD: The studies related to the prognosis of NLR and STEMI patients published in the Pubmed, Embase, and Ovid databases before June 2017 were retrieved. The relevant data were extracted. Review Manager Version 5.3 was used for meta-analysis. RESULTS: A total of 14 studies of 10,245 patients with STEMI after PCI were included. A significant difference was observed for mortality (P < 0.001; relative risk (RR) 3.32; 95% confidence interval (CI) 2.45-4.49), hospital cardiac mortality(P < 0.001; RR 3.22; 95% CI 2.25-4.60), all mortality (P < 0.001; RR 3.23; 95% CI 2.28-4.57), major adverse cardiovascular events (MACE) (P < 0.001; RR 2.00; 95% CI 1.62-2.46), in-stent thrombosis (P < 0.001; RR 2.72 95% CI 1.66-4.44), nonfatal myocardial infarction(MI) (P < 0.001; RR 1.93; 95%CI 1.43-2.61), angina (P = 0.007; RR 1.67; 95%CI 1.15-2.41), advanced heart failure (AHF) (P < 0.001; RR 1.81; 95% CI 1.48-2.21), arrhythmia (P = 0.002; RR 1.38; 95% CI 1.13-1.69), no reflow (P < 0.001; RR 2.28; 95% CI 1.46-3.57), long-term all mortality (P < 0.001; RR 3.82; 95% CI 2.94-4.96), cardiac mortality (P = 0.004; RR 3.02; 95% CI 1.41-6.45), MACE (P < 0.001; RR 2.49; 95% CI 1.47-4.23), and nonfatal MI (P = 0.46; RR 1.32; 95% CI 0.63-2.75). CONCLUSIONS: Meta-analysis shows that NLR is a predictor of hospitalization and long-term prognosis in patients with STEMI after PCI, but requires further confirmation by large randomized clinical trials.

Chemotherapeutic insensitivity remains a major obstacle to treating osteosarcoma effectively. Recently, increasing evidence has suggested that microRNAs (miRNAs) are involved in drug resistance. However, the effect of miR-138 on cisplatin chemoresistance in osteosarcoma has not been reported. We used real-time PCR to detect the expression of mature miR-138 in osteosarcoma tissues and cell lines. Cell proliferation, invasion, and migration assays were used to observe changes to the osteosarcoma malignant phenotype. MiR-138 was downregulated in osteosarcoma tissues and cell lines, and miR-138 overexpression negatively regulated osteosarcoma cell proliferation, migration, and invasion. We also verified that EZH2 is a direct target of miR-138. Furthermore, enhancing EZH2 expression reduced the inhibitory effects of miR-138 on osteosarcoma. Proliferation, apoptosis assays and caspase-3 activity assay confirmed that elevated miR-138 expression enhanced osteosarcoma cell chemosensitivity to cisplatin by targeting EZH2. In conclusion, the present study demonstrates that miR-138 acts as a tumor suppressor by enhancing osteosarcoma cell chemosensitivity and supports its potential application for treating osteosarcoma in the future.

Previous studies have demonstrated that pluripotency-associated transcription factors, such as Oct3/4, Nanog and Sox2, play a crucial role in the development and malignant progression of various types of tumors. Breast cancer is the most frequent cancer among females, being a heterogeneous disease, with distinct morphologies, metastatic behavior and therapeutic responses. The expression of Oct3/4, Nanog and Sox2 in 3 human breast cancer cell lines, MCF7, T-47D and MDA-MB-231, was determined. The expression of Oct3/4, Nanog and Sox2 mRNA was determined by reverse transcription polymerase chain reaction (RT-PCR) and protein expression was detected by immunocytohistochemistry. RT-PCR revealed that all three human breast cancer cell lines tested expressed evident Oct3/4, Nanog and Sox-2 mRNA at various levels. Higher levels of Oct3/4 were identified in MCF7 and MDA-MB-231 cells compared with T-47D cells. Higher levels of Nanog were observed in MCF7 and T-47D cells compared with MDA-MB-231 cells and the highest expression of Sox-2 was detected in MCF7 cells. The nuclear localization of Oct3/4, Nanog and Sox-2 was confirmed by immunostaining. Oct3/4, Nanog and Sox2 were expressed in human breast cancer cell lines. Further studies are required to characterize the role of Oct3/4, Nanog and Sox2 in human breast cancer.

Background N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed by m6A demethylases and recognised by m6A-binding proteins. This modification significantly influences carious facets of RNA metabolism and plays a pivotal role in cellular and physiological processes. Main body Pre-mRNA alternative splicing, a process that generates multiple splice isoforms from multi-exon genes, contributes significantly to the protein diversity in mammals. Moreover, the presence of crosstalk between m6A modification and alternative splicing, with m6A modifications on pre-mRNAs exerting regulatory control, has been established. The m6A modification modulates alternative splicing patterns by recruiting specific RNA-binding proteins (RBPs) that regulate alternative splicing or by directly influencing the interaction between RBPs and their target RNAs. Conversely, alternative splicing can impact the deposition or recognition of m6A modification on mRNAs. The integration of m6A modifications has expanded the scope of therapeutic strategies for cancer treatment, while alternative splicing offers novel insights into the mechanistic role of m6A methylation in cancer initiation and progression. Conclusion This review aims to highlight the biological functions of alternative splicing of m6A modification machinery and its implications in tumourigenesis. Furthermore, we discuss the clinical relevance of understanding m6A-dependent alternative splicing in tumour therapies.

BACKGROUND AND AIM: We previously identified forkhead box (FOX) O4 mRNA as a predictor in gastric cancer (GC). However, the underlying mechanism has yet to be elucidated. We aimed to illustrate the mechanism by which FOXO4 regulated glycolysis under hypoxia in GC. METHODS: FOXO4 protein expression was investigated by immunohistochemical staining of 252 GC and their normal adjacent tissues. We restored or silenced FOXO4 expression in GC cell lines to explore the underlying mechanisms. RESULTS: FOXO4 was downregulated in GC. Loss of FOXO4 expression was validated in univariate and multivariate survival analysis as an independent prognostic predictor for overall survival (P < 0.05) and disease-free survival (P<0.05). Restored FOXO4 expression significantly impaired the glycolysis rate in GC cells, while silencing FOXO4 expression enhanced glycolysis rate. FOXO4 expression was inversely associated with maximum standardized uptake value in mice models and patient samples. Mechanistically, FOXO4 bound to the glycolytic enzyme lactate dehydrogenase (LDH)A promoter and inactivated its activity in a dose-dependent manner (P < 0.05). Finally, we determined that FOXO4 was a transcriptional target of hypoxia-inducible factor (HIF) -1α, which is central in response to hypoxia. CONCLUSIONS: Our data suggested that FOXO4 plays a key role in the regulation of glycolysis in GC, and disrupting the HIF-1α-FOXO4-LDHA axis might be a promising therapeutic strategy for GC.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile ( NCT03141073 ).

Protein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer.

Estrogen receptor-α (ERα) is essential for estrogen-dependent growth and its level of expression is a crucial determinant of response to endocrine therapy and prognosis in ERα-positive breast cancer. Breast cancer patients show a wide range of ERα expression levels which change in individual patients during disease progression and in response to systemic therapies. However, little is known concerning how the expression of ERα is regulated in human breast cancer. Recently, several microRNAs (miRNAs) have been identified to regulate ERα expression and to predict ER, progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status. The expression levels of miR-342 and ERα mRNA were analyzed in human breast cancer samples and cell lines by quantitative reverse transcription (RT)-PCR analysis. The correlations between the expression levels of miR-342 and clinicopathological factors were analyzed. Statistically significant associations were observed between miR-342 and ER, HER2 and vascular endothelial growth factor (VEGF) status in the human breast cancer samples and the levels of miR-342 gradually increased as ERα mRNA expression increased. Moreover, ectopic overexpression of miR-342 upregulated the expression levels of the ERα mRNA and significantly sensitized the MCF-7 cells to tamoxifen-induced apoptosis and inhibition of cellular proliferation. These results suggested that miR-342 expression is positively correlated with ERα mRNA expression in human breast cancer and that it may be a significant marker for predicting tamoxifen sensitivity in ERα-positive breast cancer and a potential target for restoring ERα expression and responding to antiestrogen therapy.

Melanoma is the most lethal skin cancer characterized by its high metastatic potential. It is urgent to find novel therapy strategies to overcome this feature. Metformin has been confirmed to suppress invasion and migration of various types of cancer. However, additional mechanisms underlying the antimetastatic effect of metformin on melanoma require further investigation. Here, we performed microarray analysis and uncovered an altered mRNA and miRNA expression profile between melanoma and nevus. Luciferase reporter assay confirmed that miR-5100 targets SPINK5 to activate STAT3 phosphorylation. Migration and wound healing assays showed that the miR-5100/SPINK5/STAT3 axis promotes melanoma cell metastasis; the mechanism was proven by initiation of epithelial-mesenchymal transition. Co-immunoprecipitation (Co-IP) further confirmed an indirect interaction between SPINK5 and STAT3. Furthermore, metformin dramatically inhibited miR-5100/SPINK5/STAT3 pathway, and decreased B16-F10 cell metastasis to lung in C57 mouse module. Intriguingly, pretreatment of metformin before melanoma cell injection improved this effect further. These findings exposed the underlying mechanisms of action of metformin and update the use of this drug to prevent metastasis in melanoma.

Cardamonin is a chalcone with neuroprotective activity. The aim of our study was to explore the functions and mechanism of action of cardamonin in ischemic stroke. Oxygen-glucose deprivation and reperfusion (OGD/R)-induced human brain microvascular endothelial cells (HBMECs) and middle cerebral artery occlusion (MCAO) mouse model were utilized to mimic ischemic stroke. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide. Permeability was investigated via fluorescein isothiocyanate-dextran assay. Apoptosis was detected by TdT-Mediated dUTP Nick End Labeling staining. Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor A (VEGFA) protein levels were measured using Western blotting. Brain injury was evaluated by 2,3,5-triphenyltetrazolium chloride staining, neurological score and brain water content. The 37 overlapping targets of ischemic stroke and cardamonin were predicted to be associated with the HIF-1/VEGFA signaling. Cardamonin alleviated OGD/R-induced viability reduction and increase of permeability and apoptosis in HBMECs. Cardamonin increased OGD/R-induced activation of the HIF-1α/VEGFA pathway. Inhibition of the HIF-1α/VEGFA signaling using inhibitor relieved the effect of cardamonin on cell viability, permeability and apoptosis in HBMECs under OGD/R. Cardamonin mitigated brain injury and promoted activation of the HIF-1α/VEGFA signaling in MCAO-treated mice. Overall, cardamonin protected against OGD/R-induced HBMEC damage and MACO-induced brain injury through activating the HIF-1α/VEGFA pathway.

Osteosarcoma, a common malignancy primarily affecting children, generally has a poor prognosis. Novel diagnostic, prognostic and therapeutic markers are required to ameliorate the negative outcomes of this disease. We investigated two potential markers, WNT-5a and ROR2, which are hypothesized to dysregulate WNT signaling pathways to promote tumorigenesis in other types of cancer. We investigated WNT-5a and ROR2 expression using immunohistochemistry in 42 osteosarcoma and 12 osteochondroma specimens, and compared the expression of these proteins with one another as well as with clinicopathological parameters. WNT-5a was detected in 34/42 (81.0%) cases and ROR2 was detected in 31/42 (73.8%) cases, significantly higher than in osteochondroma (16.7 and 25.0%, respectively; both P<0.05). Expression of these proteins was positively correlated (r=0.552, P<0.05). Furthermore, expression of WNT-5a and ROR2 was both correlated with Enneking surgical stage and tumor metastasis (P<0.05), but not with patient gender, age or pathological type. Thus, WNT-5a and ROR2 were more highly expressed in more severe disease states, and therefore may play a coordinated role in the occurrence and progression of osteosarcoma.

The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target of miR-874 via its 3' untranslated region (UTR). Moreover, miR-874 was downregulated in HCC and its expression was inversely correlated with DOR expression. Downregulation of miR-874 was also associated with larger tumor size, more vascular invasion, a poor TNM stage, poor tumor differentiation, and inferior patient outcomes. Functionally, overexpression of miR-874 in the HCC cell line SK-hep-1 inhibited cell growth, migration, in vitro invasion, and in vivo tumorigenicity. Furthermore, miR-874 overexpression suppressed the DOR, resulting in a downregulated epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK) phosphorylation. The EGFR activator-epidermal growth factor (EGF)-can rescue the proliferation and migration suppression induced by miR-874 overexpression, and the rescue effects of the EGF were blocked by an ERK inhibitor. Our study results suggest that miRNA-874 is a negative regulator of the DOR that can suppress tumor proliferation and metastasis in HCC by targeting the DOR/EGFR/ERK pathway, which may be a potential target for HCC treatment.

Glycolysis is regarded as the hallmark of cancer development and progression, which involves a multistep enzymatic reaction. This study aimed to explore the clinicopathological significance and potential role of glycolytic enzyme aldolase A (ALDOA) in the carcinogenesis and progression of gastric cancer (GC). ALDOA was screened from three paired liver metastasis tissues and primary GC tissues and further explored with clinical samples and in vitro studies. The ALDOA protein level significantly correlated with a larger tumor diameter (P = .004), advanced T stage (P < .001), N stage (P < .001) and lymphovascular invasion (P = .001). Moreover, the expression of ALDOA was an independent prognostic factor for the 5-year overall survival and disease-free survival of patients with GC in both univariate and multivariate survival analyses (P < .05). Silencing the expression of ALDOA in GC cell lines significantly impaired cell growth, proliferation and invasion ability (P < .05). Knockdown of the expression of ALDOA reversed the epithelial-mesenchymal transition process. Mechanically, ALDOA could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element-luciferase activity in GC cells. Collectively, this study revealed that ALDOA was a potential biomarker of GC prognosis and was important in the carcinogenesis and progression of human GC.

Abstract Aims The H2FPEF score is a convenient risk stratification tool for diagnosing heart failure with preserved ejection fraction (HFpEF). This study examined the value of the H2FPEF score for predicting all-cause mortality and rehospitalization in HFpEF patients. Methods and results This was a retrospective cohort study of patients diagnosed with HFpEF by echocardiography at a single tertiary centre between 1 January 2015 and 30 April 2018. According to the H2FPEF score, the subjects were divided into low (0–1 points), intermediate (2–5 points), and high (6–9 points) score groups. The primary outcomes were all-cause mortality and rehospitalization. A total of 476 patients (mean age: 70.5 ± 8.4 years, 60.7% female) were included. Of these, 47 (9.9%), 262 (55.0%), and 167 (35.1%) were classified into the low, intermediate, and high score groups, respectively. Over a mean follow-up of 27.5 months, 63 patients (13.2%) died, and 311 patients (65.3%) were rehospitalized. The mortality rates were 3 (6.4%), 29 (11.1%), and 31 (18.6%), and the number of patients with rehospitalization was 28 (59.6%), 159 (60.7%), and 124 (74.3%) for the low, intermediate, and high score groups, respectively. Multivariate Cox regression identified H2FPEF score as an independent predictor of all-cause mortality (hazard ratio [HR]: 1.46, 95% CI: 1.23–1.73, P &amp;lt; 0.0001) and rehospitalization (HR: 1.15, 95% CI: 1.08–1.22, P &amp;lt; 0.0001). Receiver operating characteristic (ROC) analysis demonstrated the H2FPEF score can effectively predict all-cause mortality (AUC 0.67, 95% CI: 0.60–0.73, P &amp;lt; 0.0001) and rehospitalization (AUC 0.59, 95% CI: 0.54–0.65, P = 0.001) after adjusting for age and NYHA class. With a cut-off value of 5.5, the sensitivity and specificity were 68.3% and 55.4% for all-cause mortality and 50.5% and 66.7% for rehospitalization. Conclusions The H2FPEF score can be used to predict prognosis in HFpEF patients. Higher scores are associated with higher all-cause mortality and rehospitalization.

Due to the excellent photoluminescent properties and singlet oxygen (1O2) generating efficiency, graphene quantum dots (GQDs) with maximal emission in near-infrared region (NIR) exhibited great potential in cancer imaging and therapy. However, GQDs can be cleared quickly via the renal system in vivo because of their ultrasmall size, which leads to the compromised cancer cell killing efficacy. Here, we report a hybrid nanoplatform, where GQDs were incorporated into the cavity of hollow mesoporous silica nanoparticles (hMSN) to form GQDs@hMSN-PEG nanoparticles (NPs). Optical characterization indicated that GQDs@hMSN-PEG NPs still maintained good absorption and emission properties from GQDs, and the composite NPs still possessed similar 1O2 generating efficiency. GQDs@hMSN-PEG NPs exhibited good biocompatibility in vitro and in vivo. High cargo-loading efficiency was achieved for doxorubicin (DOX), and the formed GQDs@hMSN(DOX)-PEG NPs showed the feasibility of tumor-oriented drug delivery. The extended retention time in tumor and good drug loading efficacy confirmed that GQDs@hMSN-PEG could serve as one promising candidate for combinational cancer treatment where photodynamic therapy and chemotherapy modules can be integrated into one system.

OBJECTIVE: To investigate the efficacies of Femoral Neck System (FNS) and the three cannulated screws fixation (3CS) as therapeutic options for femoral neck fractures. METHOD: This was a retrospective study involving 69 patients (26 males and 43 females; mean age of 54.9 years (range, 28-66 years)) subjected to either FNS or 3CS for femoral neck fracture therapy. These patients were treated in our hospital from October 2019 to May 2020. Patient follow up was done at 1, 2, 3 and 6 months. During the short-term (6 months) follow-up period, surgical procedures for the two groups and incidences of complications were analyzed. Perioperative parameters were recorded and analyzed. Postoperative hip joint functions were measured and compared using the Harris score. The assessed perioperative parameters included surgical time, hemoglobin loss, fluoroscopy duration, hospitalization length and hospitalization cost. The main complications at last follow-up (6 months) included varus tilting, femoral neck shortness, and implant removal. RESULTS: Differences in the number of patients, age, Garden type of fracture and time from injury to surgery between the two groups were not significant (P > 0.05). With regards to perioperative parameters, compared to 3CS, FNS treatment performed better in surgical time (60.00 ± 12.44 vs 76.81 ± 13.10 min, P = 0.000), blood loss (13.67 ± 8.02 vs 16.58 ± 4.16 g/L, P = 0.059) and fluoroscopy time (39.73 ± 9.57 vs 58.14 ± 9.15 s, P = 0.000). Differences in hospitalization length and cost between the groups were not significant (P > 0.05). During the whole follow-up period, all patients did not exhibit dysfunction, pulmonary embolism or even death as a result of long-term immobilization of affected limbs. Surgical incisions for all patients healed well without infections. During the 6-month follow-up period, the FNS group exhibited a higher Harris score (84.61 ± 3.42 vs 78.67 ± 3.72, p = 0.000). In addition, treatment-associated complications (FNS vs 3CS) included femoral neck varus tilt (3.03% vs 11.11%), femoral neck shortness (6.06% vs 13.89%), and implant removal (0% vs. 13.89%). Implant removal rate for the FNS group was significantly less than that of the 3CS group (P = 0.026). Differences in incidences of femoral neck varus tilt (P = 0.196) and femoral neck shortness (P = 0.282) between the two groups were not significant. However, the difference in number was significant (FNS group was less). CONCLUSION: FNS treatment is associated with a smaller surgical trauma, stronger stability, and reductions in post-operative complication incidences, therefore, it is a potential therapeutic option for femoral neck fractures.

BACKGROUND: Neuropsychiatric symptoms emerged early in the COVID-19 pandemic as a key feature of the virus, with research confirming a range of neuropsychiatric manifestations linked to acute SARS-CoV-2 infection. However, the persistence of neurological symptoms in the post-acute and chronic phases remains unclear. This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning. METHODS: A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, EBSCO, and CENTRAL, up to March 22, 2024. Studies evaluating the prevalence of long-term neurological symptoms in COVID-19 survivors with at least six months of follow-up were included. Pooled prevalence estimates, subgroup analyses, and meta-regression were performed, and publication bias was assessed. RESULTS: The prevalence rates for the different symptoms were as follows: fatigue 43.3% (95% CI [36.1-50.9%]), memory disorders 27.8% (95% CI [20.1-37.1%]), cognitive impairment 27.1% (95% CI [20.4-34.9%]), sleep disorders 24.4% (95% CI [18.1-32.1%]), concentration impairment 23.8% (95% CI [17.2-31.9%]), headache 20.3% (95% CI [15-26.9%]), dizziness 16% (95% CI [9.5-25.7%]), stress 15.9% (95% CI [10.2-24%]), depression 14.0% (95% CI [10.1-19.2%]), anxiety 13.2% (95% CI [9.6-17.9%]), and migraine 13% (95% CI [2.2-49.8%]). Significant heterogeneity was observed across all symptoms. Meta-regression analysis showed higher stress, fatigue, and headache in females, and increased stress and concentration impairment with higher BMI. CONCLUSIONS: Neurological symptoms are common and persistent in COVID-19 survivors. This meta-analysis highlights the significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery. REGISTRATION AND PROTOCOL: This meta-analysis was registered in PROSPERO with registration number CRD42024576237.

BACKGROUND: The IL-4, IL-4 receptor (IL4R), and IL-13 genes are crucial immune factors and may influence the course of various diseases. In the present study, we investigated the association between the potential functional polymorphisms in IL-4, IL-4R, and IL-13 and coal workers' pneumoconiosis (CWP) risk in a Chinese population. METHODS: Six polymorphisms (C-590T in IL-4, Ile50Val, Ser478Pro, and Gln551Arg in IL-4R, C-1055T and Arg130Gln in IL-13) were genotyped and analyzed in a case-control study of 556 CWP and 541 control subjects. RESULTS: Our results revealed that the IL-4 CT/CC genotypes were associated with a significantly decreased risk of CWP (odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.58-0.95), compared with the TT genotype, particularly among subgroups of age <65 years (OR = 0.68, 95%CI = 0.46-0.99) and dust exposure years ≥26 years (OR = 0.69, 95%CI = 0.50-0.94). Moreover, the polymorphism was significantly associated with risk of CWP patients with stage I. In addition, a combined effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P(trend) = 0.023), and individuals with 11-12 risk alleles had a 47% higher risk of CWP than those with 0-8 risk alleles (OR = 1.47, 95% CI = 1.05-2.05). CONCLUSIONS: Our results suggest that the IL-4 C-590T polymorphism is involved in the etiology of CWP and susceptibility to this disease. Larger studies are warranted to validate our findings.