Objective:To investigate the factors contributing to frailty in very elderly patients with multimorbidity.Methods:This cross-sectional study enrolled 119 very elderly patients with multimorbidity who were hospitalized in the Department of Geriatrics of Huadong Hospital Affiliated to Fudan University from August 2022 to March 2023.The study aimed to understand the basic status of multimorbidity by collecting general information, the number and types of diseases, and frailty status.The subjects were divided into frail and non-frail groups through comprehensive geriatric assessment.Various factors including gender, age, Tinetti balance gait score, risk of sarcopenia, dementia, depression, risk of deep vein thrombosis, dysphagia, comorbidity index, medication count, Basic Activities of Daily Living(BADL)score, Instrumental Activities of Daily Living(IADL)score, Nutritional Risk Screening 2002(NRS-2002)score, Norton pressure injury risk assessment score, and Social Support Rating Scale(SSRS)score were compared.The correlation between each factor and the occurrence of frailty was analyzed using univariate analysis and multivariate Logistic regression analysis.Results:A total of 119 elderly inpatients with multimorbidity, with an average age of 90.8±5.9 years old, were included in the study.The incidence of frailty was 68.9%(82 cases).Univariate analysis revealed significant statistical differences between the frail group and the non-frail group in various factors including age( t=-3.131, P=0.002), Tinetti score( Z=-5.544, P<0.001), risk of sarcopenia( χ2=39.205, P<0.001), dysphagia( χ2=5.937, P=0.015), Charlson comorbidity index( Z=-2.565, P=0.010), medication count( Z=-3.325, P<0.001), BADL( Z=-5.871, P<0.001), IADL( Z=-5.062, P<0.001), Norton score( Z=-5.922, P<0.001), and SSRS social support( Z=-2.637, P=0.008).Multivariate logistic regression analysis showed that the Tinetti score( OR=0.843, 95% CI: 0.737-0.966, P=0.014), decreased muscle strength( OR=11.226, 95% CI: 2.157-58.432, P=0.004), sarcopenia( OR=18.084, 95% CI: 2.041-106.211, P=0.009), Norton score( OR=0.462, 95% CI: 0.254-0.838, P=0.011), and medication count( OR=1.153, 95% CI: 1.000-1.329, P=0.049)were independently associated with frailty. Conclusions:In very elderly patients with multimorbidities, the occurrence of frailty is notably increased.Frailty is linked to multiple risks including falls, muscle weakness/sarcopenia, pressure ulcer risk, and polypharmacy, and these risks are independent of other factors.

Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a highly conserved member of the family of leucine-rich repeat (LRR) proteins. LRG1 has been reported to be closely related to the occurrence and development of malignant tumors. Recent studies have shown that LRG1 is abnormally expressed in many digestive system tumors, including esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer. LRG1 has also been reported to be closely related to tumor cell proliferation, invasion, migration, apoptosis, and poor prognosis. This paper reviews the research progress of LRG1 in many digestive system tumors, providing new ideas for LRG1-based anti-tumor treatment.

Objective:This study aimed to investigate the role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria (PNH) patients.Methods:A retrospective analysis was conducted on the clinical data and gene sequencing results of 45 patients with classic PNH admitted to the Department of Hematology, Tianjin Medical University General Hospital, from June 2018 to February 2022. MUC4 gene mutations in patients with classic PNH were summarized, and the risk factors for thrombotic events in these patients were analyzed. Additionally, the effects of MUC4 gene mutations on the cumulative incidence and survival of thrombotic events in patients with classic PNH were determined.Results:The detection rate of MUC4 gene mutations in patients with classic PNH who experienced thrombotic events (thrombotic group) was 68.8% (11/16), which was significantly higher than that in the non-thrombotic group [10.3% (3/29) ] ( P<0.001). All mutations occurred in exon 2. MUC4 mutation ( OR=20.815, P=0.010) was identified as an independent risk factor for thrombotic events in patients with classic PNH. The cumulative incidence of thrombotic events was 78.6% (11/14) in the MUC4 gene mutation group (mutation group) and 16.1% (5/31) in the non-mutation group, showing a statistically significant difference between the two groups ( P<0.001). Survival analysis showed a lower overall survival (OS) rate in the thrombotic group compared with that in the non-thrombotic group [ (34.4±25.2) % vs. (62.7±19.3) % ] ( P=0.045). The OS rate of patients was (41.7±29.9) % in the mutation group and (59.1±18.3) % in the non-mutation group ( P=0.487) . Conclusion:MUC4 gene mutations are associated with an increased incidence of thrombotic events in classic PNH patients, highlighting their role as independent risk factors for thrombosis in this population. These mutations can be considered a novel predictive factor that aids in evaluating the risk of thrombosis in patients with classic PNH.

Objective:To explore the relationship between the expression of SF3B1, UBE2V2, SETD2 and osteoporotic vertebral fracture (OVF) in elderly patients.Methods:Peripheral blood samples were collected from 31 elderly patients with osteoporotic vertebral fractures (VF group) and 16 elderly patients with osteoporotic non-vertebral fractures (NVF group) in Yantai Mountain Hospital. RNA was extracted for transcriptome sequencing to screen for differentially expressed genes. VF related genes were screened by Gene Ontology (GO) analysis, protein protein interaction (PPI) network analysis and ROC curve analysis. Qrt-pcr was used to detect gene expression levels.Results:Compared with NVF group, 691 genes were up-regulated while 131 genes were down regulatedin VF group. qRT-PCR results revealed that, compared with NVF patients (1.55±0.33) (1.70±0.33) (1.64±0.33) , SF3B1 (1.83±0.23) ( t=2.84, P=0.008) , UBE2V2 (2.24±0.43) ( t=3.91, P<0.001) expression were increased while SETD2 (1.18±0.46) ( t=3.25, P=0.003) expression was decreased in peripheral blood of VF patients. ROC curve analysis showed that the AUCs of SF3B1, UBE2V2 and SETD2 in VF were 0.8034 ( P=0.007) , 0.8145 ( P=0.005) and 0.7863 ( P=0.0014) , respectively. Conclusion:SF3B1, UBE2V2 and SETD2 are highly correlated with OVF in elderly patients, and are of great value in the diagnosis and prediction of OVF.

Objective:To investigate the predictive value of blood routine and blood biochemical indicators for immunotherapy combined with chemotherapy-related interstitial pneumonia (IP) in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The data of 151 newly-diagnosed DLBCL patients treated with rituximab combined with chemotherapy in the First Affiliated Hospital of Soochow University from December 2017 to October 2020 were retrospectively analyzed. According to whether IP occurred, the patients were divided into IP group and non-IP group. The patient's clinical data and baseline laboratory test results were collected. The differences in clinicopathological features and laboratory indicators between IP group and non-IP group were analyzed. In addition, the relationship between the variety of blood routine and blood biochemical indicators and the occurrence of IP was analyzed. The receiver operating characteristic (ROC) curve of the selected indicators to predict the occurrence of IP was drawn, and the predictive performance of each indicator was analyzed.Results:The incidence of IP was 9.3% (14/151) in DLBCL patients after receiving immunotherapy combined with chemotherapy. The lymphocyte count (LYM) in IP group at the first diagnosis was higher than that in non-IP group [1.60×10 9/L (1.40×10 9/L, 2.51×10 9/L) vs. 1.28×10 9/L (0.89×10 9/L, 1.78×10 9/L), U=-2.194, P=0.028], but there was no significant difference in the levels of platelet count, neutrophil count, monocyte count, lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), serum albumin (ALB) and the proportion of patients with elevated C-reactive protein (CRP) between the two groups (all P > 0.05). Compared with the laboratory indicators in non-IP group before the 4th cycle of treatment, LYM and ALB in IP group were significantly reduced at IP onset [0.72×10 9/L (0.46×10 9/L, 0.92×10 9/L) vs. 0.93×10 9/L (0.71×10 9/L, 1.15×10 9/L), 32.9 g/L (28.6 g/L, 34.9 g/L) vs. 40.3 g/L (36.1 g/L, 43.1 g/L)], but LDH and α-HBDH increased [332 U/L (255 U/L, 396 U/L) vs. 233 U/L (200 U/L, 286 U/L), 277 U/L (206 U/L, 315 U/L) vs. 189 U/L (159 U/L, 229 U/L)], and the differences were statistically significant (all P<0.05). The proportion of patients with elevated CRP in IP group was high than that in non-IP group [100.0% (14/14) vs. 56.9% (78/137), P=0.001]. The area under ROC curve of LYM, ALB, LDH and α-HBDH alone for predicting the occurrence of IP was 0.668, 0.820, 0.789 and 0.802. The best cut-off values of ALB, LDH and α-HBDH was 34.6 g/L, 241 U/L and 199 U/L. ALB had the highest sensitivity for predicting the occurrence of IP (81.8%). The areas under ROC curve of ALB+LDH, ALB+α-HBDH, LDH+α-HBDH, ALB+LDH+α-HBDH for predicting the occurrence of IP was 0.850, 0.844, 0.777 and 0.851, respectively. LDH+α-HBDH had the highest predictive sensitivity (92.9%), but the specificity was low (53.3%). The prediction sensitivity (both 78.6%) and specificity (both 86.1%) of ALB+LDH and ALB+LDH+α-HBDH were high. Conclusions:DLBCL patients are at risk of IP during immunotherapy combined with chemotherapy. The increased LYM at initial diagnosis is a risk factor for the occurrence of IP. The variety of LYM, ALB, LDH, α-HBDH and CRP during the treatment may be related to the occurrence of IP. Among them, ALB, LDH and α-HBDH have important predictive values for the occurrence of IP.

Objective To observe the visual field loss after 577 nm krypton pan-retinal photocoagulation (PRP) in the treatment of diabetic retinopathy (DR).Methods A prospective clinical studies.Forty-six eyes of 26 patients with proliferative DR (PDR) and severe non-proliferative DR (NPDR) diagnosed by clinical examination from No.306 Hospital of PLA during January 2014 and December 2015 were included in this study.Among them,21 eyes of NPDR and 20 eyes of PDR;13 eyes with diabetic macular edema (DME) (DME group) and 28 eyes without DME (non-DME group).All eyes underwent best corrected visual acuity (BCVA),fundus color photography,fundus fluorescein angiography (FFA) and optical coherence tomography (SD-OCT) examinations.The visual field index (VFI) and visual field mean defect (MD) values were recorded by Humphrey-7401 automatic visual field examination (center 30° visual field).The BCVA of DR eyes was 0.81 ± 0.28;the VFI and MD values were (89.8± 8.4)％ and-7.5 ± 3.85 dB,respectively.The BCVA of the eyes in the without DME group and DME group were 0.92±0.20 and 0.57±0.27,the VFI were (90.86±7.86)％ and (87.46± 9.41)％,the MD values were-6.86± 3.43 and 8.87 ± 4.48 dB.PRP was performed on eyes using 577 nm krypton laser.The changes of VFI,MD and BCVA were observed at 1,3,and 6 months after treatment.Results Compared with before treatment,the VFI of DR eyes decreased by 12.0％,12.3％ and 14.8％ (t=7.423,4.549,4.79;P＜0.001);the MD values were increased by-4.55,-4.75,6.07 dB (t=-8.221,-5.313,-5.383;P＜0.001) at 1,3 and 6 months after treatment,the differences were statistically significant.There was no difference on VFI (t=1.090,-0.486;P＞0.05) and MD value (t=-0.560,-0.337;P＞0.05) at different time points after treatment.Compared with before treatment,the BCVA was significantly decreased in DR eyes at 1 month after treatment,the difference was statistically significant (t=2.871,P＜0.05).Before and after treatment,the BCVA of the DME group was lower than that of the non-DME group,the difference were statistically significant (t=4.560,2.848,3.608,5.694;P＜0.001);but there was no differences on the VFI (t=1.209,0.449,0.922,0.271;P＞0.05) and MD values (t=1.582,0.776,0.927,1.098;P＞0.05) between the two groups.Conclusion The range of 30° visual field loss is about 12％-14.8％ after 577 nm krypton laser PRP for DR.VFI and MD can quantitatively analyze the and extent of visual field loss after PRP treatment.

Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (C_trough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers’ group (30 cases) and poor metabolizers’ group (35 cases). The C_trough of the 65 patients were detected for 169 times totally, and there was a significant difference of C_trough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of C_trough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ²=11.689, P=0.020). Conclusion Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their C_trough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.

Objective To establish methods for the determination of spinosin and total saponins in compound Zaoshen tablet .Methods The separation of spinosin was performed on Agilent Zorbax SB C18 column (250 mm × 4 .6 mm ,5 μm) at 30℃ with water and acetonitrile as mobile phase for gradient elution at the flow rate of 1 .0 ml/min .The detection wavelength was 335 nm .Determination of total saponins was fulfilled by column chromatography followed by UV spectrometer with vanil-lin glacial acetic acid colorimetry .The detection wavelength was 560 nm .Results Linear range of spinosin was 20-100 μg/ml (r=0 .9990) and total saponins was 40-200 μg/ml (r=1 .0000) .The average recoveries for accuracy tests were 99 .55% and 99 .85% respectively .Conclusion Those methods are accurate and reliable .They can be used for the quality control of com-pound Zaoshen tablet .

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs)and anti-angio-genic drugs have individually demonstrated clinical benefit in the treatment of patients with advanced non-small cell lung cancer (NSCLC).Recent studies demonstrate that the combination of anti-EGFR and anti-angiogene-sis can more significantly enhance clinical benefit,and even can remit EGFR-TKIs resistance in the treatment of advanced NSCLC.According to the different kinds of anti-angiogenesis drugs,recent clinical studies mainly include the combination of anti-vascular endothelial growth factor monoclonal antibody bevacizumab plus EGFR-TKIs and multi-targeted receptor anti-angiogenic tyrosine kinase inhibitor plus EGFR-TKIs,and the for-mer results show a more significant improvement in terms of safety and efficacy in the treatment of advanced NSCLC.Therefore,the combination of bevacizumab plus EGFR-TKIs can be used as a new treatment standard in the treatment of some patients with NSCLC.

Objective: To investigate the change of autophagy level of bone marrow nucleated red blood cell (RBC) in patients with myelodysplastic syndromes (MDS) . Methods: Fifty-four MDS patients and thirty-three controls were enrolled in this study. The mitophagy were observed by transmission electron microscopy (TEM) . The level of autophagy-associated protein LC3B in GlycoA⁺ nucleated RBC was measured by flow cytometry. The expressions of ULK1 and mTOR mRNA in GlycoA⁺ nucleated RBC were measured by real-time PCR. The expression of the mitochondrial outer membrane protein TOM20 in GlycoA⁺ nucleated RBC was detected by Western blot. Results: Autophagosomes or autolysosomes were scarcely observed by TEM in MDS patients. The expression of LC3B in GlycoA⁺ nucleated RBC in high-risk MDS patients (0.22±0.12) was significantly lower than that in normal controls (0.43±0.22, P<0.001) , and lower than that in low-risk MDS patients (0.40±0.16, P=0.001) . The expression of AMPK [0.26 (0.60) ] in GlycoA⁺ nucleated RBC in high-risk MDS patients was significantly lower than that in controls [1.00 (2.07) , P<0.017) . The expression of ULK1 mRNA in GlycoA⁺ nucleated RBC in high-risk MDS patients [0.27 (3.31) ] was significantly lower than that in controls [1.07 (4.41) , P<0.017]. The level of mTOR mRNA in GlycoA⁺ nucleated RBC in high-risk MDS patients [1.82 (3.74) ] was significantly higher than that in controls [1.26 (1.38) , P<0.017]. The level of LC3B in GlycoA⁺ nucleated RBC was negatively correlated with the HGB (r=0.529, P=0.009) in high-risk MDS patients. The expression of mitochondrial outer membrane protein TOM20 in high-risk MDS patients was 9.42±4.42. Conclusion Autophagy is impaired in nucleated RBC of MDS patients.