Objective To investigate the role and underlying mechanisms of WD repeat domain 82 (WDR82) protein in the pathogenesis and progression of glioma. Methods We analyzed the expression level of WDR82 in glioma tissues using GEPIA and UALCAN databases and further assessed WDR82 protein expression in glioma and adjacent normal tissues through immunohistochemical staining. The correlation between WDR82 expression and the prognosis of glioma patient was evaluated using Kaplan-Meier plotter. Experiments were conducted on A172 and U251 cell lines, which were categorized into four groups: control group (transfected with 3 μg pcDNA3), shR-control group (transfected with 3 μg pSilencer 2.1-U6), pWDR82 group (transfected with 3 μg pWDR82), and shR-WDR82 group (transfected with 3 μg shR-WDR82). Post-transfection, we confirmed transfection efficiency at 48 hours using qRT-PCR and measured cell viability at the same time point with CCK-8 assay. Clone formation assay was employed to assess cell proliferation capacity after 14 days of transfection, while flow cytometry was utilized to analyze cell apoptosis after 48 hours of transfection. Additionally, Western blotting was conducted to determine the expression levels of proteins related to proliferation and Akt/mTOR signaling pathway after 48 hours of transfection. Finally, the effect of WDR82 on tumor growth in NOD-SCID mice was investigated using tumor carrying experiment in vivo. Results Analysis of WDR82 expression in glioma tissues using GEPIA and UALCAN databases, along with immunohistochemical staining, revealed significantly higher expression levels compared to normal and paracancerous tissues (P<0.05). Additionally, WDR82 expression was not associated with gender or age of patients (P>0.05). Kaplan-Meier plotter analysis indicated that elevated WDR82 expression correlated with a poor prognosis in glioma patients (log-rank P=0.029). Overexpression of WDR82 notably enhanced the proliferation and inhibited the apoptosis of A172 and U251 cells, and also significantly upregulated the expression of MKI67, BCL2, CCND1, p-Akt and p-mTOR in A172 and U251 cells (P<0.05). Conversely, WDR82 knockdown had the opposite effects, inhibiting cell proliferation, increasing apoptosis and downregulating the expression of MKI67, BCL2, CCND1, p-Akt and p-mTOR (P<0.05). WDR82 knockdown in U251 cells significantly inhibited tumor growth in NOD-SCID mice (P<0.05). Conclusion High expression of WDR82 promotes the proliferation of glioma cells and the growth of tumors in vivo by regulating the AKT/mTOR signaling pathway.

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease, and hip preservation surgery has high clinical value in the early stages of ONFH, especially for young and middle-aged patients. However, the repair of ONFH is heterogeneous, leading to inter-individual variations in the efficacy of hip preservation. Currently, the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation, making it difficult to achieve precise repair. Smart responsive materials have good biocompatibility and self-feedback capability. By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems, new possibilities are provided for the precise repair of ONFH. This paper reviews the research progress of smart responsive materials at home and abroad. Based on the response principles of various materials and the repair characteristics of ONFH, the application prospects of various smart responsive materials such as reactive oxygen species-responsive, fluid shear stress-responsive, and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH, providing new ideas for the precise treatment of ONFH.

Non-small cell lung cancer ( NSCLC ) is one of the most prevalent and deadly malignant tumors in the world. In recent years, artificial intelligence (AI) in computed tomography (CT) has harnessed the power of big data to automatically extract and learn imaging features, thereby assisting radiologists in reducing the workload and missed diagnosis rate of pulmonary nodules. An ELISA kit for detecting seven lung cancer autoantibodies (p53, SOX2, PGP9.5, CAGE, MAGE-A1, GAGE7, and GBU4-5) has been clinically implemented in China, showing high specificity in the early screening of NSCLC. Additionally, other liquid biopsy techniques such as circulating tumor DNA (ctDNA) methylation markers are also continually being explored. However, existing methods for the early diagnosis of lung cancer all have their limitations, and optimizing their combination or establishing diagnostic models has become a trend. This review summarizes the research progress and value of the seven lung cancer autoantibodies and CT AI in the early diagnosis of NSCLC, with the aim of providing a reference for their combined use in the early diagnosis of lung cancer in Chinese population.

Exertional heat stroke (EHS) is the most serious and life-threatening acute heat-related illness. It can develop from heat-related illnesses, and the prehospital management is a crucial in the diagnosis and treatment of EHS. The prognosis of EHS patients is largely determined by the rapid recognition, effective cooling, and standardized transportation during the prehospital period. Extensive research has demonstrated that medical security personnel still have fatal misconceptions in the prehospital recognition and management of EHS, mainly due to the lack of recognition and inappropriate treatment. This review summarizes the top 10 misconceptions in prehospital recognition and management of EHS, based on domestic and international research findings and combined with practical scenarios. It also provides an accurate prehospital management plan according to the China Expert Consensus on Diagnosis and Treatment of Heatstroke, aiming to reduce or avoid irreversible damage to EHS patients caused by these misunderstandings and to decrease the incidence, disability rate, and mortality rate of EHS.

Objective To investigate the risk factors for early neurological deterioration (END) following intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) acute mild ischemic stroke (AMIS) patients. Methods Eighty-six patients with AMIS who underwent intravenous thrombolysis with rt-PA in the Department of Neurology, Civil Aviation General Hospital between January 2019 and October 2022 were retrospectively analyzed. Patients were categorized into END group (n=8) and non-END group (n=78) based on the presence of END within 24 hours after thrombolysis (NIHSS score increased by ≥2 points within 24 hours after intravenous thrombolysis). Baseline characteristics, including age, gender, past medical history (hypertension, diabetes, hyperlipidemia, etc.), smoking history, pre-thrombolysis NIHSS score, homocysteine level, fibrinogen level, and post-thrombolysis bleeding transformation were documented for each patient. A multivariate logistic regression analysis was conducted to access the risk factors associated with END following intravenous thrombolysis in AMIS. Results There were significant differences in homocysteine and fibrinogen levels, as well as bleeding transformation after thrombolysis between the two groups (P<0.05). In contrast, other factors such as age, gender, past medical history, pre-thrombolysis NIHSS score, and other imaging features were not statistically significant (P>0.05). Multivariate logistic regression analysis revealed that elevated homocysteine level was independently linked to risk of END after intravenous thrombolysis in AMIS, with an odds ratio of 1.074(95%CI 1.011-1.142, P=0.021). Conclusions Hyperhomocysteinemia emerges as an independent risk factor for END following intravenous thrombolysis in patients with AMIS.

Objective To investigate the short-term efficacy and safety of chemotherapy induced by nimotuzumab (NTZ) combined with TP regimen and sequential concurrent chemoradiotherapy in patients with epidermal growth factor receptor positive(EGFR-positive) locally advanced nasopharyngeal carcinoma. Methods A total of 48 patients with stage Ⅲ to IV A nasopharyngeal carcinoma in Guizhou Provincial People's Hospital from January 2020 to December 2022 were prospectively enrolled, and were randomized into two groups: NTP (NTZ+docetaxel/albumin-paclitaxel+cisplatin) group and TP (Docetaxel/albumin-paclitaxel+cisplatin) group(24 cases per group) by random number table method. After 2 or 3 cycles of induction chemotherapy in NTP group, NTZ was sequentially used in combination with cisplatin for concurrent chemoradiotherapy. Immunohistochemistry was used to detect the EGFR expression level, exploring EGFR expression intensity and the therapeutic effect of NTZ in NTP group patients. Meanwhile, short-term efficacy, withdrawal rate and toxic side effects were compared between the two groups after induction chemotherapy. Results In NTP group, the positive expression rate of EGFR was 100%, and EGFR expression intensity significantly correlated with the efficacy of NTZ-combined induction therapy (P<0.05). After induction chemotherapy, the objective response rate (ORR) of cervical lymph nodes in NTP group was significantly higher than that in TP group (75% vs. 45.8%, P=0.039). The primary lesion ORR and overall (primary lesion and cervical lymph node) ORR showed no significant difference between the two groups (P>0.05). Comparison of adverse reactions between the two groups during induction therapy: leukopenia and gastrointestinal reaction in NTP group were lower than those in TP group (P<0.05), but rash was higher than those in TP group (P<0.05). There was no significant difference in liver function, hemoglobin and thrombocytopenia between two groups (P>0.05). Conclusions EGFR expression intensity varies in nasopharyngeal carcinoma tissues, with higher levels indicating greater clinical benefit of combined induction therapy with NTZ. NTZ combined with TP induction regimen demonstrates good short-term efficacy and safety for cervical lymph nodes in patients with locally advanced nasopharyngeal carcinoma.

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms. Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) database from 2008 to 2019. According to the occurrence of posttraumatic fatal massive hemorrhage, the patients were divided into two groups: fatal massive hemorrhage group (n=283) and non-fatal massive hemorrhage group (n=7239). Six machine learning algorithms, including logistic regression (LR), support vector machine (SVM), random forests (RF), adaptive boosting (AdaBoost), gated recurrent unit (GRU), and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma. The probability of fatal massive hemorrhage in the following 1, 2, and 3 h was dynamically predicted. The performance of the models was evaluated by accuracy, sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under receiver operating characteristic curve (AUC). The models were externally validated based on the trauma database of the Chinese PLA General Hospital. Results In the MIMIC-Ⅳ database, the set of dynamic prediction models based on the GRU-D algorithm was the best. The AUC for predicting fatal major bleeding in the next 1, 2, and 3 h were 0.946±0.029, 0.940±0.032, and 0.943±0.034, respectively, and there was no significant difference (P=0.905). In the trauma dataset, GRU-D model achieved the best external validation effect. The AUC for predicting fatal major bleeding in the next 1, 2, and 3 h were 0.779±0.013, 0.780±0.008, and 0.778±0.009, respectively, and there was no significant difference (P=0.181). This set of models was deployed in a public web calculator and hospital emergency department information system, which is convenient for the public and medical staff to use and validate the model. Conclusion A set of dynamic prediction models has been successfully developed and validated, which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

Objective To investigate the causal relationship between obstructive sleep apnea (OSA) and hypertension using bidirectional Mendelian randomization (MR). Methods Genetic data for OSA were obtained from the Genome-wide association study (GWAS) of FinnGen Biobank, including 16 761 cases and 201 194 controls, from which 5 single-nucleotide polymorphisms (SNPs) were screened as instrumental variables (IVs) for OSA. Genetic data for hypertension were obtained from GWAS of UK Biobank, including 124 227 cases and 337 653 controls from which 214 SNPs were selected as IVs for hypertension. Multiple MR methods, mainly Inverse variance weighted (IVW), were used for analysis. Sensitivity analysis of MR results was performed using MR-Egger regression et al, and IVs were evaluated using F values. Results OSA was associated with an increased risk of hypertension (OR=1.053, 95%CI 1.019-1.089, P<0.01), and hypertension was significantly associated with the risk of developing OSA (OR=1.812, 95%CI 1.354-2.425, P<0.001). Heterogeneity was observed in both two-way outcomes (OSA→ hypertension, P<0.001; hypertension→ OSA, P<0.001), but no evidence of horizontal pleiotropy was detected (OSA→ hypertension, P=0.666; hypertension→ OSA, P=0.556). The IVs selected in this study were strong instrumental variables for both OSA and hypertension (OSA-IVs F=14.695; hypertension-IVs F=39.624). Conclusions Our findings indicate a bidirectional causal relationship between OSA and hypertension, with a particularly significant effect of hypertension on the development of OSA.

Objective To elucidate the clinical significance of high expression levels of endonuclease meiosis 1 (EME1) in the prognosis of hepatocellular carcinoma (HCC). Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to screen and analyze differential gene expression between HCC and non-tumor tissues. A retrospective collection of liver tissue samples from 80 HCC patients who underwent hepatectomy in the Fifth Medical Center of Chinese PLA General Hospital between January 2010 and December 2014 was performed. Immunohistochemistry analysis was employed to detect the EME1 expression levels. Survival analysis was then conducted to assess the impact of EME1 expression on 5-year postoperative survival rate of HCC patients. Additionally, gene enrichment analysis was applied to predict the function of EME1 in HCC. Results A total of 371 HCC tissue samples and 50 non-tumor liver tissue samples from TCGA database were analyzed, revealing significantly higher EME1 expression in HCC tissues. Microarray analysis of 107 samples within the GEO database (70 HCC tissues and 37 non-tumor tissues) confirmed that EME1 mRNA expression was markedly elevated in HCC tissues compared with non-tumor tissues (P<0.05). The 5-year overall survival (OS) rate was notably lower in high EME1 expression group than that in low expression group (44.1% vs. 53.0%, P<0.05). Semi-quantitative immunohistochemistry analysis demonstrated that patients with high EME1 expression had a significantly lower OS rate than those with low EME1 expression (32.8% vs. 45.0%, P<0.05). Multivariate COX regression analysis identified that high EME1 expression (HR=2.234, 95%CI 1.073-4.649, P=0.032) and advanced China liver caner (CNLC) staging (HR=4.317, 95%CI 1.799-10.359, P=0.001) were independent risk factors for the 5-year OS of post-operation patients with HCC. Conclusion Elevated EME1 expression in HCC tissues correlates with an adverse prognosis of HCC and suggests that EME1 could serve as a potential therapeutic target for HCC.

Objective To report the clinicopathological features, gene mutation sites, diagnosis and treatment of a case of hereditary myopathy with early respiratory failure (HMERF), and review the literature to enhance the understanding of the disease. Methods A retrospective analysis was conducted on the clinical data, imaging examinations, histopathological and genetic sequencing results, as well as the diagnosis and treatment of a case of HMERF as the initial presenting symptom, admitted to Sichuan Provincial People's Hospital in April 2021. The clinical characteristics of Chinese patients with HMERF were summarized in conjunction with literature reports. Results This patient presented with limb weakness and progressive dyspnea. Magnetic resonance imaging (MRI) showed selective fat infiltration of the medial head of calf gastrocnemius muscle. Two mutation sites in titin (TTN) gene inherited from both parents were identified, exon 341 c.94828G>A (P.a31610t) and exon 50 c.14915C>T (P.S.4972L), leading to the diagnosis of HMERF. The patient received supportive therapy. The PubMed database was searched and 15 cases of HMERF were diagnosed in Chinese patients over the past decade. The onset age of these patients was (26.1±17.0) years, predominantly affecting males. All patients exhibited mutations in TTN gene. The most prevalent mutation was identified as c.95195C>T (p.P31732L), followed by c.95134T>C (p.C31712R). Conclusions HMERF is a rare genetic disease caused by genetic mutation, with skeletal muscle weakness and respiratory muscle weakness as the main clinical manifestations. Clinical symptoms can be atypical, and exon 344 of TTN gene is a common mutation site. The mutation sites in this case, located at exon 341 c.94828G>A (P.a31610t) and exon 50 c.14915C>T (P.S4972L) of the TTN gene, may represent novel genetic markers for HMERF.