Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy. The oncolytic influenza A virus, although promising in preclinical investigations, remains to be implemented in clinical practice. Recent progress in genetic engineering, coupled with experiential insights, offers opportunities to enhance the therapeutic efficacy of the influenza A virus. This review explores the use of the influenza virus, its attenuated forms, and associated vaccines in cancer immunotherapy, highlighting their respective advantages and challenges. We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors, aiming to maximize their clinical impact. Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.
Humans ; Neoplasms/immunology* ; Immunotherapy/trends* ; Influenza A virus/immunology* ; Oncolytic Virotherapy/trends* ; Animals ; Cancer Vaccines/therapeutic use* ; Oncolytic Viruses ; Genetic Engineering ; Immune Checkpoint Inhibitors/therapeutic use*

CyberKnife has the characteristics of good repeatability of radiotherapy target,high precision and less trauma.It is a stereotactic body radiation therapy system for real-time tracking of moving tumors during treatment.For intrahepatic tumors being highly affected by respiratory movements in treatment,CyberKnife provides precise positioning,planning,and treatment.This paper focuses on the treatment of hepatocellular carcinoma(HCC)using CyberKnife,and reviews as following:the structure and iteration of CyberKnife;image-tracking modes and their advantages and disadvantages;tracking modes of common fiducial markers and their optimization methods,the positioning problems after the implantation of fiducial markers.

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 investigate the second-hand smoke behavior at home among smokers, so as to provide the reference for developing home tobacco control strategies. Methods: Permanent residents who were smokers and at the ages of 15 years and above were sampled from 10 streets (townships) in Xuhui District, Shanghai Municipality using the multi-stage random sampling and population-size proportional sampling methods in 2022. Demographic information, smoking status, awareness of second-hand smoke hazards and second-hand smoke behavior at home were collected by questionnaire surveys. Factors affecting second-hand smoke behavior at home were identified using a multivariable logistic regression model. Results: A total of 1 024 smokers were surveyed, including 769 males (75.10%) and 255 females (24.90%). The awareness of hazards of second-hand smoke was 33.59%; the awareness rate of second-hand smoke causing lung cancer in adults was the highest at 76.76%, while the awareness rate of second-hand smoke leading to premature birth and low birth weight in newborns was the lowest at 39.45%. There were 459 smokers with second-hand smoke behavior at home, accounting for 44.82%. Multivariable logistic regression analysis showed that occupation (the retired, OR=2.320, 95%CI: 1.276-4.218), frequency of smoking (often, OR=5.722, 95%CI: 3.977-8.231), smoking duration (a year and above, OR=10.089, 95%CI: 5.508-18.480), electronic cigarette use (occasionally, OR=2.994, 95%CI: 1.283-6.986), living with pregnant women or infants (no, OR=2.171, 95%CI: 1.367-3.448), family indoor smoking restrictions (no restriction, OR=13.926, 95%CI: 7.538-25.727) and awareness of second-hand smoke hazards (unknown, OR=1.562, 95%CI: 1.067-2.287) were the influencing factors for second-hand smoke behavior at home. Conclusion There were 44.82% smokers in Xuhui District with second-hand smoke behavior at home, which was influenced by occupation, living situation, smoking status, family indoor smoking restriction and awareness of second-hand smoke hazards.

Objective:To analyze the clinical characteristics, muscle imaging and pathological features of patients with anti-signal recognition particle positive immune-mediated necrotizing myopathy (SRP-IMNM).Methods:Nine patients with SRP-IMNM were collected in the Neuromuscular Disease Center of Jiaozuo People′s Hospital from May 2018 to May 2023, who were confirmed by skeletal muscle pathology and myositis-specific autoantibodies detection, and their clinical manifestations, muscle imaging and muscle pathology characteristics were systematically summarized.Results:Among the 9 patients with SRP-IMNM, there were 7 females and 2 males. The age of onset ranged from 18 to 59 years. All the patients presented proximal muscle weakness. Seven patients experienced neck weakness, and dysphagia was present in 5 patients. Laboratory examinations showed elevated serum creatine kinase levels in all 9 patients (1 866-6 725 U/L). Eight patients were combined with other antibodies positivity, except for anti-SRP antibody. Among them, 7 patients were combined with anti-Ro-52 antibody positivity, 4 patients combined with anti-Ro-52 antibody positivity alone, and 3 patients combined with 3 or more positive antibodies simultaneously. Those patients who presented with interstitial lung disease and cardiac involvement were all combined with other antibodies positivity. Seven patients completed thigh muscle magnetic resonance imaging (MRI), which showed diffuse skeletal muscle oedema, partial muscle atrophy and fatty replacement, primarily affecting the posterior thigh muscle group. Two patients underwent shank muscle MRI. The soleus involvement was evident, while the tibialis anterior muscle and gastrocnemius muscles were involved in 1 patient. All 9 patients showed varying degrees of scattered muscle fiber necrosis and regeneration on muscle biopsies. In 1 patient, a small amount of inflammatory cell infiltration was observed. Pipestem capillaries were observed in 4 patients. Immunohistochemical staining revealed a small number of CD68-positive lymphocytes in 8 patients. Additionally, 5 patients showed upregulation of major histocompatibility complex Ⅰ expression on the muscle fiber membrane, while 6 patients showed deposition of membrane attack complex (C5b-9) on non-necrotic muscle fibers and capillaries. P62 staining showed homogeneous fine-granular in sarcoplasm in 6 patients.Conclusions:In addition to proximal muscle weakness, patients with SRP-IMNM often experience neck weakness and dysphagia. Those with multiple antibodies are more likely to develop interstitial lung disease and cardiac involvement. SRP-IMNM patients have diffuse oedema in the affected muscles, and the posterior thigh muscles are more prone to atrophy and fatty tissue formation. C5b-9 deposition and pipestem capillaries are significant pathological features of SRP-IMNM, which provide additional evidence for clinical diagnosis.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Birth cohort is an important observational study which can continuously and dynamically collect the exposure changes and health outcomes from gametophyte development to adolescence and even old age. However, because of its complex design and difficult implementation, how to construct birth cohort with high quality and high efficiency is the main difficulty faced by epidemiologists at home and abroad. In 2016, China National Birth Cohort was officially launched. The network and information technology were used to explore, and a set of "cloud-based information platform" was established to support this queue construction, containing 16 units in China. After four years of development, the platform has formed a complete set of programs about the construction of cohort information platform, which including recruitment and follow-up management of participants, real-time data interaction, queue quality control, multi-level authority management and function division. The relevant design framework and functional elements provide the references to the future information construction of large-scale birth cohort and even population-based research in China.

Objective:To investigate the association between estradiol on the day of human chorionic gonadotropin (HCG) administration and birth outcomes among singleton live births following fresh embryo transfers.Methods:Based on the clinical reproduction medicine management system of the First Affiliated Hospital of Nanjing Medical University, this retrospective cohort study collected data of fresh embryo transfer cycles during January 2013 and December 2016, including pregnant women’s age, body mass index (BMI), type and cause of infertility, assisted reproductive therapy indicators (fertilization mode, ovulation stimulation protocol, estradiol levels on HCG administration day), adverse birth outcomes[small for gestational age (SGA), premature and low birth weight (LBW)], etc.. A total of 2 060 women with singleton pregnancy (2 061 fresh embryo transfer cycles) were enrolled. Multivariate logistic regression was used to analyze the association between estradiol on HCG administration day and singletons’ adverse birth outcomes.Results:The age and BMI of the 2 060 pregnant women were (29.63±3.92) years old and (22.29±2.86) kg/m 2. Incidences of SGA, premature and LBW were 9.8% (201/2 061), 6.9% (143/2 061) and 3.5% (73/2 061), respectively. After adjusting for confounders, the risk of LBW in 4 000-4 499 pg/ml group was significantly elevated when compared to estradiol<1 500 pg/ml group [ OR (95% CI): 4.42 (1.13-17.24)]. A protective effect of premature was observed in estradiol≥4 500 pg/ml group [ OR (95% CI): 0.50 (0.25-0.97)]. Conclusion:The high level of estradiol on HCG administration day might be a risk factor for LBW, but a protective factor for premature.

Objective:To investigate the association between estradiol on the day of human chorionic gonadotropin (HCG) administration and birth outcomes among singleton live births following fresh embryo transfers.Methods:Based on the clinical reproduction medicine management system of the First Affiliated Hospital of Nanjing Medical University, this retrospective cohort study collected data of fresh embryo transfer cycles during January 2013 and December 2016, including pregnant women’s age, body mass index (BMI), type and cause of infertility, assisted reproductive therapy indicators (fertilization mode, ovulation stimulation protocol, estradiol levels on HCG administration day), adverse birth outcomes[small for gestational age (SGA), premature and low birth weight (LBW)], etc.. A total of 2 060 women with singleton pregnancy (2 061 fresh embryo transfer cycles) were enrolled. Multivariate logistic regression was used to analyze the association between estradiol on HCG administration day and singletons’ adverse birth outcomes.Results:The age and BMI of the 2 060 pregnant women were (29.63±3.92) years old and (22.29±2.86) kg/m 2. Incidences of SGA, premature and LBW were 9.8% (201/2 061), 6.9% (143/2 061) and 3.5% (73/2 061), respectively. After adjusting for confounders, the risk of LBW in 4 000-4 499 pg/ml group was significantly elevated when compared to estradiol<1 500 pg/ml group [ OR (95% CI): 4.42 (1.13-17.24)]. A protective effect of premature was observed in estradiol≥4 500 pg/ml group [ OR (95% CI): 0.50 (0.25-0.97)]. Conclusion:The high level of estradiol on HCG administration day might be a risk factor for LBW, but a protective factor for premature.