ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

There are millions of patients with taxane-induced peripheral neuropathy （TIPN）， and there is no effective treatment or prevention measure in clinical practice. The occurrence of TIPN may be related to the dosage form of paclitaxel drugs， genetic and molecular markers， drug dosage and chemotherapy cycle， patient factors， etc. At present， drugs for treating TIPN mainly include those that inhibit axonal degeneration （such as dosazosin， tamsulosin）， prevent mitochondrial dysfunction （such as glutathione trisulfides， antioxidants α -lipoic acid）， improve calcium imbalance in the internal environment （Shaoyao gancao decoction， N-type voltage-gated calcium channel inhibitor IPPQ）， and inhibit neuroinflammation （such as chemokine inhibitors and selective interleukin-8 receptor inhibitors DF2726A）. Further exploration of drug treatment strategies targeting different induction mechanisms is expected to become a new direction for precise clinical prevention and personalized treatment of TIPN.

Objective To explore the relationship between baseline urinary protein levels and the onset of chronic obstructive pulmonary disease (COPD). Methods A questionnaire survey, blood and urine sample collection, physical examination, and pulmonary function test were conducted among permanent residents over 40 years old in Pudong New Area, Shanghai. The subjects were divided into four groups based on the baseline urine albumin-to-creatinine ratio (ACR) quartiles (0~1.65 mg/g, 1.65~4.89 mg/g, 4.89~10.78 mg/g, and ≥10.78 mg/g). Cox regression analysis was used to explore the relationship between ACR levels and the incidence of COPD in middle-aged and elderly people. Results Among the 3 105 subjects, the median follow-up time was 3.212 years (P25~P75：3.102~3.473). 116 new cases of COPD were observed, with an incidence density of 10.423 per 1000 person-years. The incidence densities for COPD at four ACR levels were 7.922 per 1 000 person-years, 8.300 per 1 000 person-years , 11.419 per 1 000 person-years, and 13.843 per 1 000 person-years, respectively. Cox regression analysis revealed that as the ACR level increased, there was a rising trend in the incidence rate of COPD (χ²=4.396, P=0.036). After adjusting for gender, age, education level, occupational exposure to dust, history of childhood pneumonia, smoking, family history of COPD, central obesity, and hypertension, the risk of developing COPD was 2.499 times higher (95% CI: 1.460~4.276) for ACR levels ≥10.78 mg/g compared to the reference group with a baseline ACR level of 0~1.65 mg/g. Conclusion Elevated ACR levels in middle-aged and elderly population may increase the risk of COPD, and early monitoring of urine protein levels is beneficial for COPD prevention.

ObjectiveTo evaluate the intervention effect of meteorological risk forecasting service on acute onset and medical expenses of chronic obstructive pulmonary disease（COPD） patients， and to provide scientific basis for the establishment of health management model for chronic obstructive pulmonary disease（COPD） patients. MethodsStudy subjects were recruited from chronic obstructive pulmonary patients aged ≥40 in Pudong New Area. Propensity score matching method was used to determine the intervention group and the control group. The control group received regular health education and follow-up management， and the intervention group was provided with meteorological and environmental risk forecasting services through WeChat， mobile phone short message service（SMS）and telephone. Finally， a total of2 589 subjects were included in the analysis， including 1 300 in the intervention group and 1 289 in the control group. General demographic data， past medical history and family history of COPD， COPD related knowledge and practice survey， COPD related symptom assessment， acute onset， health service utilization and medical expenses before and after intervention were collected through questionnaire survey. The differences of acute attack， health service utilization and related medical expenses between the two groups before and after intervention were compared to evaluate the intervention effect. ResultsIn terms of acute attacks， after intervention， the incidence of acute attacks in the intervention group was lower than that before intervention（χ²=52.901， P<0.001）， and the incidence of acute attacks in the groups with different intervention methods was lower than that before intervention （P<0.001）. WeChat had the best effect， decreasing the incidence by 14.4%， followed by mobile phone SMS SMS decreasing by 12.3%. In terms of utilization of health services， the outpatient rate due to acute attack was lower in the intervention group after intervention than that before intervention （χ²=7.129， P=0.008）， and the outpatient rate due to acute attack was lower in the subjects who received the forecast service through mobile phone SMS than that before intervention （χ²=4.675， P<0.001）. In terms of medical expenses， there was no significant difference between control group and intervention group with different intervention methods before intervention （P>0.05）. After intervention， the difference between the control group and the intervention group with different intervention methods was statistically significant （H=11.864， P<0.05）. The results of multiple comparisons showed that compared with the control group， the average annual medical expenses of patients receiving mobile phone SMS and telephone forecasting services after intervention were lower than those of the control group， and the difference was statistically significant （P<0.05）. ConclusionMeteorological risk forecasting service can reduce the acute onset of COPD， reduce the rate of consultation and medical expenses due to acute onset， and provide scientific basis for the basic COPD health management model.

With the high-speed growing demands for biomedical materials, graphene oxide(GO) and its functional derivatives show broad application prospects in the system of drug delivery, tumor therapy and nanobiology. GO has excellent hydrophilicity and easily modified surface properties, due to a large content of oxygen-containing functional groups on the GO surface. Meanwhile, the huge specific surface areas and unique π-electronic structures give GO adhesion and adsorption capacities. By means of π-π stacking, electrostatic interaction, hydrophobic interaction or covalent bonding, therapeutic agents can be effectively combined with GO to construct drug delivery systems. GO plays an important role in transdermal drug delivery systems due to their biocompatibility, antibacterial activity, and pro-wound healing activity. As a novel drug delivery system, GO nanomaterials can achieve targeted drug delivery, accumulate drug concentrations at the focal site, and improve drug delivery efficiency. Utilizing the promoting skin regeneration and wound healing properties of GO, several antibacterial materials and wound dressings are prepared for wound treatment. In addition, the special far-infrared resonance effect and electrothermal effect of GO result in heat and electric transfer. In other words, graphene oxide could control and promote transdermal absorption efficiency upon the stimuli of heat and electric. GO is expected to break through the limitation of low transdermal absorption rates in the transdermal drug delivery systems and achieve the purpose of enhancing the transdermal permeability of target molecules (especially macromolecules): ultimately improving bioavailability in vivo. This paper will introduce the structures, physicochemical properties, and biological activities of graphene oxide, summarize its application in transdermal drug delivery systems such as drug carriers, antibacterial materials, wound dressings and transdermal enhancers, and prospect its application in clinical medicine. We hope to provide new ideas and different point of views for the biomedical research of graphene oxide and derivatives. GO will become a representative biomaterial in the field of precision medicine and play a key role in the diagnosis and treatment of diseases.

Objective:To investigate the value of intratumoral and peritumoral radiomics models based on 18F-FDG PET-CT in predicting epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma and interpret peritumoral radiomics features. Methods:This study was a cross-sectional study. Patients with lung adenocarcinoma who underwent 18F-FDG PET-CT at the Third Affiliated Hospital of Soochow University between January 2018 and April 2022 were retrospectively collected and samplied into a training set (309 cases) and a test set (206 cases) in a 6∶4 ratio randomly. Radiomics features were extracted from the intratumoral and peritumoral regions of interest based on PET and CT images, respectively, and the optimal feature sets were selected. Radiomics models were established using the XGBoost algorithm, and radiomics scores (intratumoral CT label, peritumoral CT label, intratumoral PET label, peritumoral PET label) were calculated. Logistic regression analysis was used to construct a clinical model and a combined model (incorporating PET-CT intratumoral and peritumoral radiomics, clinical features, and CT semantic features). The predictive performance of the models was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Unsupervised clustering, Spearman correlation analysis, and visualization methods were used for the interpretability of peritumoral radiomics features. Results:In both the training and test sets, the AUC value of CT peritumoral labels was greater than that of CT intratumoral labels for predicting EGFR mutation status in lung adenocarcinoma (training set: Z=3.84, P<0.001; test set: Z=1.99, P=0.046). In the test set, the AUC value of PET intratumoral labels (0.684) was slightly higher than that of PET peritumoral labels (0.672) for predicting EGFR mutation status, but the difference was not statistically significant ( P>0.05). The combined model had the highest AUC value for predicting EGFR mutation status of lung adenocarcinoma in both the training and test sets and was significantly better than the clinical model (training set: Z=6.52, P<0.001; test set: Z=2.31, P=0.021). Interpretability analysis revealed that CT peritumoral radiomics features were correlated with CT shape features, and there were significant differences in CT peritumoral features between different EGFR mutation statuses. Conclusions:The value of CT peritumoral labels is superior to that of CT intratumoral labels in predicting EGFR mutation status in lung adenocarcinoma. The predictive performance of the model can be improved by combining PET-CT intratumoral and peritumoral radiomics, clinical features, and CT semantic features.

BACKGROUND: Lung cancer has been the leading cause of cancer-related deaths worldwide for many years. This study aimed to investigate the global patterns and trends of lung cancer. METHODS: Lung cancer incidence and mortality were derived from the GLOBOCAN 2020 database. Continuous data from Cancer Incidence in Five Continents Time Trends were used to analyze the temporal trends from 2000 to 2012 using Joinpoint regression, and average annual percent changes were calculated. The association between the Human Development Index and lung cancer incidence and mortality was assessed by linear regression. RESULTS: An estimated 2.2 million new lung cancer cases and 1.8 million lung cancer-related deaths occurred in 2020. The age-standardized incidence rate (ASIR) ranged from 36.8 per 100,000 in Demark to 5.9 per 100,000 in Mexico. The age-standardized mortality rate (ASMR) varied from 32.8 per 100,000 in Poland to 4.9 per 100,000 in Mexico. Both ASIR and ASMR were approximately twice higher in men than in women. The ASIR of lung cancer showed a downward trend in the United States of America (USA) between 2000 and 2012, and was more prominent in men. The age-specific incidence rates of lung cancer for ages of 50 to 59 years showed an upward trend in China for both men and women. CONCLUSIONS The burden of lung cancer is still unsatisfactory, especially in developing countries like China. Considering the effectiveness of tobacco control and screening in developed countries, such as the USA, there is a need to strengthen health education, accelerate the establishment of tobacco control policies and regulations, and improve early cancer screening awareness to reduce the future burden of lung cancer.
Male ; Humans ; Female ; United States ; Middle Aged ; Incidence ; Lung Neoplasms/epidemiology* ; Linear Models ; China/epidemiology*

Objective:To analyze the molecular mechanism of Zhenqi Fuzheng Capsules in the adjuvant treatment of AIDS by network pharmacology method and molecular docking technology.Methods:The active components and targets of Zhenqi Fuzheng Capsules were obtained through TCMSP, and the AIDS-related targets were obtained through GeneCards, OMIM and DrugBank databases. The intersection target PPI network was constructed through STRING 11.5 database, and Cytoscape 3.9.1 software was used for network topology analysis; Metascape database was used for GO function and KEGG pathway enrichment analysis of core targets; Cytoscape 3.9.1 was used to construct Zhenqi Fuzheng Capsules component-target-pathway network; Autodock Tools software was used to carry out molecular docking of core targets and active components.Results:Totally 31 active components and 180 targets of Zhenqi Fuzheng Capsules were screened out. TNF, IL6, AKT1, IL1B, TP53, VEGFA, RELA, EGFR and CASP3 were identified as the core targets. GO functional enrichment analysis obtained 1 436 biological processes, 53 cellular components, and 117 molecular functions. KEGG pathway enrichment analysis obtained 167 pathways, which were related to pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, and IL-17 signaling pathway was closely related. Molecular docking results showed that core targets such as AKT1 and TNF had good binding activity to quercetin, kaempferol, and luteolin.Conclusion:The main active components of Zhenqi Fuzheng Capsules in the adjuvant treatment of AIDS are quercetin, kaempferol and luteolin, which may treat AIDS through the IL-17 signaling pathway.

Objective:To investigate the diagnostic values of human epididymis protein 4 (HE4), endothelial cell specific molecule-1 (ESM-1) and epidermal growth factor receptor (EGFR) for lung cancer.Methods:The clinical data of 90 patients with lung cancer and 50 patients with benign lung diseases diagnosed by the pathological examination in Tangshan People's Hospital from December 2019 to January 2021 were retrospectively analyzed, and 40 healthy physical examiners in the same period were selected as the controls. The serum HE4 levels were detected by electrochemiluminescence method. The serum ESM-1 and EGFR levels were tested by enzyme-linked immunosorbent assay. The differences in serum HE4, ESM-1 and EGFR levels between the three groups were compared; logistic regression analysis was used to screen out the effective indicators for the diagnosis of lung cancer and to construct a prediction model for the diagnosis of lung cancer. Using pathological diagnosis result as the gold standard, the receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of indicators for lung cancer was evaluated.Results:The levels of serum HE4 in lung cancer group, benign lung diseases group and healthy control group were 119.55 pmol/L (82.06 pmol/L, 189.00 pmol/L), 58.84 pmol/L (45.62 pmol/L, 69.41 pmol/L) and 42.67 pmol/L (37.09 pmol/L, 51.84 pmol/L), the levels of ESM-1 were 33.00 ng/ml (25.85 ng/ml, 47.40 ng/ml), 20.14 ng/ml (11.93 ng/ml, 28.90 ng/ml) and 15.39 ng/ml (11.84 ng/ml, 20.19 ng/ml), and the levels of EGFR were 46.60 pg/ml (37.45 pg/ml, 58.98 pg/ml), 32.77 pg/ml (26.27 pg/ml, 40.86 pg/ml) and 30.43 pg/ml (27.54 pg/ml, 35.75 pg/ml), and the differences in each indicator among the three groups were statistically significant (all P < 0.001). The levels of serum HE4, ESM-1 and EGFR in lung cancer group were higher than those in benign lung diseases group and healthy control group. In patients with lung cancer, logistic regression analysis was performed with HE4 (X 1), ESM-1 (X 2) and EGFR (X 3) as the independent variables and pathological diagnosis as the dependent variable, and a lung cancer prediction regression model was established: P = 0.171X 1+0.351X 2+0.184X 3-24.660. The accuracy of this model in predicting lung cancer could reach 98.5%, and serum HE4, ESM-1 and EGFR were risk factors for the occurrence of lung cancer (all P < 0.05). The area under ROC curve from high to low was HE4 (0.960), ESM-1 (0.942) and EGFR (0.859). The diagnostic sensitivity of serum HE4 63.67 pmol/L for lung cancer was 86.7%, and the specificity was 97.5%. Both serum HE4 ( r = 0.304, P = 0.004) and ESM-1 ( r = 0.416, P < 0.001) were correlated with EGFR. Conclusions:Serum HE4, ESM-1 and EGFR can be used as effective indicators for the diagnosis of lung cancer, and the prediction model established based on the three serum tumor markers is of good value for the diagnosis and prediction of lung cancer.

Objective:To analyze the genetic counseling characteristics and interpretation of pathogenic variants for mitochondrial hearing loss.Methods:We analyzed a total of 513 unrelated families from Chinese Deafness Genome Project (CDGP), in which previous gene testing had found no pathogenic mutations with hearing loss (HL) related to the nuclear genes. We used targeted testing and complete mtDNA sequencing for the families′ available members.Results:Among the first individuals of the families to be tested, 20 cases (16 probands and 4 normal hearing consultants) were discovered with variants in mtDNA, including m.1095T>C, m.1310C>T, m.1494C>T and m.1555A>G in MT-RNR1, m.7445A>G, m.7505T>C, m.7510T>C and m.7511T>C in MT-TS1, and m.3243A>G in MT-TL1. We identified MT-RNR1 and MT-TS1 variants occurred as homoplasmic changes, while MT-TL1 variants occurred as heteroplasmic changes. Most mitochondrial hearing loss were characterized by slope or flat moderate to profound sensorineural HL. HL associated with the mtDNA pathogenic variant was variable onset age, severity and audiometric configuration. The penetrance for HL in individuals with the m.1095T>C variant might be low. Progression in the severity of HL was caused by the m.7445A>G pathogenic variant and the patients with m.7505T>C had cookie bite HL. MT-TL1 m.3243A>G was a common spot for pathogenic variants associated with nonsyndromic HL as well as syndromic HL with diabetes mellitus. Conclusions:Individuals with the mtDNA variants and their maternal relatives have a higher risk of HL and phenotypic heterogeneity in the age of onset, progression, and level of HL. The medical history should include review of any audiological testing of the probands and their family members on a maternal mtDNA background. The process of genetic evaluation needs rule out nuclear gene mutations and analyzes the genetic load of mitochondrial pathogenic variants in the probands or consultants. In these cases, we rely on clinical and genetic evaluation molecular analysis to appropriately counsel families for whom an exact cause of HL and to help them make informed medical decisions.