Objective Differentially expressed genes in oral squamous cell carcinoma (OSCC) were subjected to bioinformatic and Mendelian randomization analyses to elucidate their prognostic significance in OSCC. Methods The TCGA database and dataset GSE138206 were used to screen the common differential genes of OSCC, and their relationship was analyzed by using Mendelian randomization. The prognostic value of differential genes was further analyzed by Cox risk regression. The biological function of genes with high prognostic value was further evaluated by single gene differential analysis. Results A total of 147 common differential genes were screened from the two databases. Results of two-sample Mendelian randomization showed that GREM2 was associated with the increased risk of OSCC. In addition, SH3BGRL2 was associated with a decreased risk of OSCC, and DKK1, CCL11, and HOXC6 were considered as independent prognostic markers of OSCC. The predicted results of DKK1 were consistent with the actual results. KEGG enrichment analysis indicated the potential involvement of DKK1 in arachidonic acid and linoleic acid metabolism. Furthermore, DKK1 showed positive correlations with Tgd and Th2 cells, while displaying negative associations with PDC, Cytotoxic cells, Mast cells, CD8 T cells, TFH cells, B cells, T cells, and Th17 cells. Conclusion GREM2 is associated with an increased risk of OSCC. DKK1 is highly expressed in OSCC and associated with poor prognosis, which may be involved in regulating the metabolism of arachidonic acid and linoleic acid and immune cell invasion in OSCC.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

AIM: To observe the changes of corneal densitometry(CD)and higher-order aberrations after small incision lenticule extraction(SMILE), and to explore their correlations and influencing factors.METHODS: Prospective study. A total of 62 high-degree myopia and compound myopic astigmatism patients(62 eyes)who underwent SMILE in Urumqi Aier Eye Hospital from December 2022 to November 2023 were collected. The CD, root mean square of corneal higher-order aberrations(RMS HOA), spherical aberration, vertical coma, horizontal coma, and corneal epithelial thickness(CET)of the patients were measured before surgery, and at 1 d, 1 wk, 1, 3, and 6 mo after surgery, respectively.RESULTS:There were 4 patients lost to follow-up during the period, all due to failure to attend scheduled reexaminations. The number of complete and valid cases was 58 eyes. The CD in the central and paracentral regions of the anterior, middle, and total layer of the cornea increased significantly on the first day after surgery(all P<0.003). At 6 mo after surgery, there was a slight but statistically significant decrease in the CD of the central and paracentral regions of the anterior and the total anterior layer(all P<0.003). Compared with the preoperative baseline values, the RMS HOA, spherical aberration, and vertical coma significantly increased at 6 mo after surgery(all P<0.003), while the change in horizontal coma was not statistically significant. Compared with the preoperative baseline values, the CET in the central, paracentral, and peripheral regions of the cornea, as well as the total average CET in the 0-7 mm range of the cornea increased at 6 mo after surgery(all P<0.003). At 1 d after surgery, CD of the anterior layer and total layer in the central region of the cornea were positively correlated with the CET in the central region(rs=0.327, rs=0.250, all P<0.05). At 6 mo after the surgery, the CD of the middle layer and posterior layer in the central corneal region were negatively correlated with the preoperative spherical equivalent and the change of RMS HOA(all P<0.05).CONCLUSION:The anterior CD decreases at 6 mo after SMILE for high myopia correction, and there is a certain correlation between the changes in CD and some clinical parameters.

BACKGROUND: Urolithiasis is a widespread disease with a high prevalence worldwide. This study aims to evaluate the disease burden of urolithiasis and its trends from 1990 to 2021 globally, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. METHODS: The numbers and age-standardized rates (ASRs) of incidence, disability-adjusted life years (DALYs), and mortality of urolithiasis were extracted from GBD 2021 to represent the disease burden. Joinpoint regression analyses were conducted to assess the temporal trends in the burden of urolithiasis. The male-to-female ASR ratio indices were used to evaluate sex disparities. Additionally, we explored the relationship between the ASR ratio and the sociodemographic index (SDI). RESULTS: The total numbers of incidence, DALY, and mortality of urolithiasis were 105,983,780 cases (95% uncertainty interval [UI] = 88,349,356-128,645,155 cases), 693,444 cases (95% UI = 567,765-850,490 cases), and 17,672 cases (95% UI = 13,932-21,241 cases), respectively, in 2021. There is an increasing trend in the number of these measures globally, whereas the ASRs have decreased over the past 30 years. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were significantly higher in males than in females in 2021. The sex disparities in the age-standardized DALY rate (ASDR) and ASMR of urolithiasis were negatively correlated with the SDI. In 2021, the ASIR of urolithiasis was 964.70 (95% UI = 801.26-1175.09) per 100,000 people in China, which is much lower than the global average (1242.84 [95% UI = 1034.94-1506.99] per 100,000 people). Compared with the global average, a more pronounced decline in ASIR was observed in China from 1793.16 (1446.0-2235.14) in 1990 to 964.70 (801.26-1175.09) per 100,000 people in 2021. CONCLUSIONS Urolithiasis poses a significant healthcare burden worldwide. More robust global and national strategies are warranted to address the prevention and treatment, especially in low SDI countries and regions.
Humans ; Urolithiasis/mortality* ; Male ; Female ; Incidence ; Global Burden of Disease ; Disability-Adjusted Life Years ; Adult ; Middle Aged ; Risk Factors ; Sex Factors

Objective:To investigate optimal treatment strategy for pT3N0 laryngeal squamous cell carcinoma（SCC）. Methods:A retrospective study of 150 patients with pT3N0 laryngeal SCC treated in the First Affiliated Hospital of Chongqing Medical University was performed. The efficacies of partial laryngectomy and total laryngectomy, as well as surgery alone and postoperative radiotherapy were evaluated. The overall survival（OS）, disease specific survival（DSS） and disease-free survival（DFS） were analyzed with statistical package from SPSS. Results:Among the 108 patients with glottic laryngeal SCC, there were no significant differences in OS, DSS and DFS between the partial laryngectomy group and the total laryngectomy group（Log-rank=0.184, 0.010 and 0.051, P>0.05）. Similarly, there were no significant differences in OS, DSS and DFS between the surgery-alone group and postoperative radiotherapy group（Log-rank=0.214, 0.251 and 0.003, P>0.05）. Among the 38 patients with supraglottic laryngeal SCC, the OS in the total laryngectomy group was significantly higher than that in the partial laryngectomy group（Log-rank=7.338, P=0.007）. The DSS and DFS in the total laryngectomy group were higher than in the partial laryngectomy group, but the differences were not statistically significant（Log-rank=0.895 and 1.792; P>0.05）. The DFS in the postoperative radiotherapy group was significantly higher than in the surgery-alone group（Log-rank=7.172, P=0.007）, but there were no significant differences in OS and DSS between these two groups（Log-rank=0.010 and 0.876, P>0.05）. Conclusion:For pT3N0 glottic laryngeal cancer patients, the efficacy of partial laryngectomy is comparable to total laryngectomy, same as surgery alone and postoperative radiotherapy. For pT3N0 supraglottic laryngeal cancer patients, total laryngectomy could improve the overall survival, and postoperative radiotherapy could reduce the recurrence. Prospectively randomized study with large samples is still needed.
Humans ; Laryngeal Neoplasms/therapy* ; Laryngectomy/methods* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Male ; Female ; Middle Aged ; Disease-Free Survival ; Neoplasm Staging ; Aged ; Survival Rate ; Treatment Outcome

Obesity is a well-established risk factor for thrombotic events such as venous thromboembolism， and the alterations in pharmacokinetics induced by obesity pose challenges for anticoagulation management. This article systematically reviews the advances of the use of various anticoagulants in obese patients， and finds that the dosage of low-molecular-weight heparin needs to be adjusted according to preventive or therapeutic goals in severely obese patients， the preventive dose may be increased to 40 mg， q12 h or 0.5 mg/（kg·d）， while the therapeutic dose is recommended to be reduced to 0.8 mg/（kg·d）， q12 h. Direct oral anticoagulant drugs are safe and effective for general obese patients； in severely obese patients， standard doses of rivaroxaban or apixaban may be used， warranting cautious application and consideration for therapeutic drug monitoring. In special clinical scenarios such as obesity combined with trauma， pregnancy， advanced age， or bariatric surgery， anticoagulation strategies should be individualized， with close attention to monitoring. Future research should focus on optimizing anticoagulant regimens for special populations and addressing anticoagulation management in obese patients with other embolic diseases.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To investigate the differences in clinical and electrocardiographic characteristics between carriers of SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome.Methods:This study is a retrospective cohort study. A total of 263 patients with fever-induced Brugada syndrome who were admitted to Renmin Hospital of Wuhan University from January 2000 to December 2023 were selected. Their clinical manifestations, electrocardiographic characteristics, and major adverse cardiovascular events (MACE) at the time of diagnosis and during the follow-up period were collected. Among them, 200 patients underwent next-generation sequencing. Based on the genetic variation results, after excluding other mutations, they were divided into SCN5A mutation group, non-SCN5A sodium-related mutation group, potassium/calcium mutation group, and no mutation group. Comparisons were made among these groups in terms of their clinical and electrocardiographic characteristics.Results:Among the 263 patients with fever-induced Brugada syndrome, the mean age was (41.9±17.6) years, with 80.6% (212/263) being male. The median follow-up duration was 53.0 months, and 13.7% (36/263) of the patients experienced MACE. The rate of SCN5A mutation was 34.5% (69/200), while the rates of non-SCN5A sodium-related mutations and potassium/calcium-related mutations were 4.5% (9/200) and 3.5% (7/200), respectively. The SCN5A mutation group was younger than the non-SCN5A sodium-related mutation group and the no mutation group (ages were (33.8±14.7), (49.8±11.6), (44.6±15.7) years, respectively, P<0.001). The SCN5A mutation group also had a longer PR interval than the no mutation group ((176.8±32.3) ms vs. (163.9±28.6) ms, P=0.034). The incidence of MACE was higher in the non-SCN5A sodium-related mutation group than that in the no mutation group (55.6% (5/9) vs. 9.1% (9/99), P=0.002). Conclusions:Fever-induced Brugada syndrome patients carrying non-SCN5A mutations exhibit distinct clinical and electrocardiographic characteristics compared to those with SCN5A mutations. These differences warrant attention in clinical practice.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Kidney stones is the most common urinary system disease, among which calcium oxalate stones are the most common. The pharmacological treatment of calcium oxalate stones currently in use is associated with low compliance and a high incidence of adverse reactions. In recent years, plant extracts have demonstrated considerable potential in inhibiting renal calcium oxalate stones. This article introduces the role of plant extracts, including polysaccharides, polyphenols, alkaloids, flavonoids and organic acids, in the inhibition of calcium oxalate stones. It also provides a theoretical basis for the clinical prevention and treatment of calcium oxalate stones.