Retinoblastoma is a kind of malignant eye tumor commonly seen in children, which is one of the main causes threatening children's vision and life. The diagnosis and evaluation of retinoblastoma has always been a hot topic in clinic. In the past few years, the application of artificial intelligence(AI)technology has made significant progress in the medical field, providing new opportunities and challenges for the diagnosis and treatment of retinoblastoma, for example, the use of AI algorithms to analyze massive clinical data, which can help doctors diagnose the disease more accurately and provide personalized treatment plans. In addition, AI technology also plays an important role in medical image analysis, genomics research and other aspects, which can help the development of new drugs and improve patient prognosis. This article reviews the application progress of AI in retinoblastoma.

Objective:To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation.Methods:A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS.Results:A total of 169 patients with EGFR rare mutations were included, and the age [ M (IQR)] was 63 years (12 years); there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years; 70 (41.4%)males and 99 (58.6%) females; 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation; 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55); in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups ( χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups ( P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups ( P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation; brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024; unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions:Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.

  Objective  To identify the risk factors for postoperative nausea and vomiting (PONV) in surgical patients undergoing patient controlled intravenous analgesia (PCIA).  Methods  Our study was a retrospective cohort study, including patients who underwent surgery at Peking Union Medical College Hospital from July 1 to October 31, 2023 and received PCIA after surgery. Patient characteristics, medical history, surgical information, intraoperative medication information, postoperative analgesia follow-up information were obtained through the electronic medical record system. The patients were divided into PCIA-PONV group and non-PCIA-PONV group, depending on the occurrence of PONV during PCIA, and all patients were also divided into PCIA-POV group and non-PCIA-POV according to whether postoperative vomiting (POV) occurred. Multivariate Logistic regression analysis was used to identify the risk factors for PCIA-PONV and PCIA-POV.  Results  A total of 1373 patients were included in this study, with 676 cases in PCIA-PONV group. The incidence of PCIA-PONV was 49.2%. There were 285 patients in PCIA-POV group, and the incidence of PCIA-POV was 20.8%. The results of multivariate Logistic regression analysis showed that female (OR=2.134, 95% CI: 1.590-2.865, P < 0.001) and abdominal surgery (OR=1.655, 95% CI: 1.253-2.186, P < 0.001) were risk factors for PCIA-PONV, whereas the increase of age (OR=0.990, 95% CI: 0.982-0.998, P=0.019) and the increase of BMI (OR=0.961, 95% CI: 0.932-0.991, P=0.012) were protective factors for PCIA-PONV. Female (OR=2.646, 95% CI: 1.754-3.992, P < 0.001), history of general anesthesia (OR=1.372, 95% CI: 1.042-1.806, P=0.024), and intraoperative use of high-dose opioids (OR=1.607, 95% CI: 1.206-2.142, P=0.001) were risk factors for PCIA-POV, whereas no intraoperative use of neuromuscular blocking antagonists (OR=0.393, 95% CI: 0.237-0.651, P < 0.001) was protective factor for PCIA-POV.  Conclusions  Our study reveals the risk factors for PONV in surgical patients undergoing PCIA, and shows that comprehensive preoperative assessment and reasonable perioperative management strategies are significant in the prevention of PCIA-PONV.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective:To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+ ).Methods:Three GEFS+ probands and their pedigree members presented at the Children′s Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants.Results:Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c. 1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c. 2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c. 1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Conclusion:The c. 1613T>C, c. 2804A>G and c. 1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.

The goal of Medical Immunology is to enable students to pay attention to integration of immunology theory with clini-cal practice,be familiar with professional English,consciously pay attention to cutting-edge knowledge,and can learn independently and lifelong.However,existing teaching models lack explanation of clinical disease related events,and arrangement of experimental content and projects is seriously disconnected from clinical practice,scientific research on solving clinical problems is clearly insuffi-cient.We established a"B to B"cycle model for immunology teaching by starting from clinical practical problems(Bedside),return to basic research(Bench),and then solve clinical problem(Bedside),which will comprehensively cultivate senior medical profession-als with clinical competence,scientific research thinking ability,innovative spirit,and international perspective.

Objective:To explore significance of eosinophil and eosinophil/lymphocyte ratio(ELR)in predicting allergic asth-ma in children in different seasons.Methods:Retrospective analysis of children with asthma who visited pediatric respiratory depart-ment outpatient clinic and ward of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2021 to December 2021,whose allergen specific IgE(sIgE)and peripheral blood cell analysis were complete.sIgE≥0.35 kUA/L were included in allergic asthma group,sIgE<0.35 kUA/L and total allergen IgE<60 kUA/L were included in non-allergic asthma group.General data and changes in peripheral blood cells of two groups were analyzed.Results:There were 1 378 qualified subjeats,including 999(72.5%)in allergic asthma group and 379(27.5%)in non-allergic asthma group.Number of visits in allergic asthma group varied seasonally,with the most in autumn.Peripheral blood lymphocyte count(LYMPH),eosinophil count(EOS)and ELR were all higher in children with allergic asthma than in children with non-allergic asthma(P<0.05),and platelet/lymphocyte ratio(PLR)was lower than that in children with non-allergic asthma(P<0.05).Peripheral blood LYMPH,PLT,EOS and ELR of children with allergic asthma differed between four seasons,which were higher than those of non-allergic asthma in each season in EOS and ELR,LYMPH was significantly higher than that of children with non-allergic asthma in autumn,and PLT was significantly lower than that of children with non-allergic asthma in spring(P<0.05).EOS predicted AUC of spring,summer,autumn and winter were 0.79,0.77,0.71 and 0.64 in children with allergic asthma,and ELR predicted AUC were 0.72,0.48,0.73 and 0.68 in children with allergic asthma.Conclusion:Allergic asthma in children is seasonally variable and peaks in autumn.EOS and ELR in peripheral blood cells in children with allergic asthma are higher than in children with non-allergic asthma in each season of year,LYMPH is significantly higher than children with non-allergic asthma in the fall,and PLT is lower than in children with non-allergic asthma in spring,suggesting that allergic asthma type Ⅱinflammation persists,and EOS and ELR have predictive value for children's allergic asthma.

Based on high-resolution magnetic resonance tube wall imaging,reverse medical engineering modeling techniques are used to obtain individualized intracranial artery models of high prevalence in ischemic stroke.Three types of intracranial artery models,including Newtonian fluid model,non-Newtonian fluid model and non-Newtonian fluid with two-phase flow model,are established for transient numerical simulations using computational fluid dynamics method.The hemodynamic parameters such as blood flow field,wall shear stress distribution and erythrocyte volume distribution are analyzed to investigate the possible mechanisms involved in the formation and progression of intracranial atherosclerosis.It is found that blood flow velocity increased significantly at the end of the internal carotid artery and the middle cerebral artery.Low-speed vortex flow and disturbed flow appear in the local vessels.The difference in blood flow velocity between the center and the edge of the wall is large,with an obvious low-flow velocity area on the outer side.A clear central core area is formed in the stenotic wall under the action of high-speed blood flow,resulting in thinner edge layer and lower erythrocyte volume fraction.The combination of low erythrocyte distribution in the edge layer and low flow velocity on the outer side of the wall exacerbates endothelial cell necrosis,hypoxia,endothelial dysfunction,and leads to atherosclerosis.Compared with Newtonian and non-Newtonian fluid models,non-Newtonian fluid with two-phase flow model has greater variability for hemodynamic parameters and shows higher fidelity in simulating blood flow,which provides a reference for clinical diagnosis and treatment of cerebrovascular diseases.

OBJECTIVE: The medicinal mushroom Sanghuangporus vaninii produces pharmaceutically valuable hispidin polyphenols in natural habitats. However, due to the slow growth in nature, S. vaninii grown in the field (sclerotia) is not reliable for pharmaceutical purposes. Although higher biomass of fungal mycelia can be obtained in submerged cultures, the accumulation of hispidin polyphenols is rare. METHODS: In this study, the polyunsaturated fatty acids (PUFAs), linoleic acid (LA), linolenic acid (ALA), and methyl jasmonate (MeJa) were employed as the stimulant agents to coordinate the accumulation of biomass and hispidin polyphenols in its submerged cultures. RESULTS: The addition of LA and ALA promoted the mycelial accumulation, while the addition of MeJa inhibited the growth of S. vaninii concomitant with reduced total polyphenols. UPLC-Triple-TOF-MS analysis revealed an increased production of hispidin, phellinstatin, pinnilidine, and its derivatives upon the addition of LA and ALA, and hypholomine B and its isomer, 3,14'-bihispidinyl, and phelligridin E upon the addition of MeJa on day 13. Intriguingly, total polyphenols from the MeJa-supplementing cultures harbored a high capacity in scavenging free radicals. Chemical structural analysis showed that hispidin polyphenols had higher antioxidant activity due to more hispidin moieties induced by MeJa. CONCLUSION The supplement of PUFAs affects the synthesis and composition of hispidin polyphenols in S. vaninii. Our results provide a possibility to coordinate the production of hispidin polyphenols via submerged cultures of S. vaninii.