Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer.

BACKGROUND: Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer. METHODS: The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography-mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice. RESULTS: GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1. CONCLUSIONS: Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.

[Overexpression of LncRNA MEG3 promotes ferroptosis and enhances chemotherapy sensitivity of hepatocellular carcinoma cells to cisplatin].

OBJECTIVE: To investigate the effect of overexpression of LncRNA MEG3 on proliferation, migration and cisplatin sensitivity of hepatoma cells HepG2 and LM3 and explore the underlying and mechanism. METHODS: The expression of MEG3 in healthy individuals and patients with hepatocellular carcinoma (HCC) was analyzed by online bioinformatics analysis, and Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect MEG3 expression in different HCC cell lines. A MEG3-overexpresing plasmid was transfected in HepG2 and LM3 cells, and the changes in cell proliferation and migration were examined using CCK8 assay and scratch assay. CCK8 assay was used to determine the inhibitory rate of cisplatin on the transfected cells. A reactive oxygen species (ROS) fluorescence probe (DCFH-DA) and malondialdehyde (MDA) kit were used to assess the changes in ROS production and MDA level in the cells. Western blotting was performed to detect the expression levels of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). RESULTS: The expression of MEG3 was significantly lower in HCC cells than in LO2 cells, which was consistent with the results of bioinformatic analysis (P < 0.05). Overexpression of MEG3 in the HCC cell lines significantly suppressed cell proliferation and migration (P < 0.05), increased the cell inhibition rate of cisplatin (P < 0.05), enhanced cellular ROS production and increased MDA levels in the cells (P < 0.05). MEG3 overexpression significantly decreased the expressions of GPX4 and FTH1 in the HCC cell lines. CONCLUSION: The expression of MEG3 is decreased in HCC cells, and its overexpression inhibits proliferation and migration and enhances cisplatin sensitivity of HCC cells by promoting ferroptosis of the cells.

[Analysis of the correlative factors of long-term positive nucleic acid and the characteristics of nucleic acid conversion in novel coronavirus infected patients].

To analyze the correlative factors of long-term positive nucleic acid and the characteristics of negative nucleic acid conversion in novel coronavirus infected patients.Novel coronavirus infected patients who were hospitalized in Beijing Tsinghua Changgung Hospital from December 2022 to June 2023 were retrospectively included. Patients who were positive for novel coronavirus nucleic acid for ≥30 days were selected as the long-positive group, and age-and sex-matched patients with novel coronavirus nucleic acid for <30 days were selected as the control group. The clinical data of all enrolled patients were collected. Binary logistic regression was used to analyze the influencing factors of the positive duration of nucleic acid ≥30 days. The Cox risk ratio model was used to analyze the risk factors for the prognosis of severe patients during hospitalization, and the difference in the time of nucleic acid conversion between the upper and lower respiratory tract was compared between the groups. A total of 30 patients were included in the long-positive group, including 24 males and 6 females, aged [M (Q1, Q3)] 77 (64, 86) years. Fifty-eight patients were included in the control group, including 46 males and 12 females, aged 78 (66, 86) years. Transplantation status (OR=50.32, 95%CI: 1.98-1 278.63, P=0.018), malignant tumor (OR=12.85, 95%CI: 1.65-99.88, P=0.015), CD4+T cell count (OR=0.99, 95%CI: 0.99-1.00, P=0.005) were correlative factors for positive nucleic acid≥30 days. Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score (HR=1.12, 95%CI: 1.03-1.22, P=0.012) and nucleic acid positive time (HR=1.16, 95%CI: 1.01-1.33, P=0.031) were correlative factors for death in severe patients. The nucleic acid conversion time of the lower respiratory tract specimens in both groups was later than that of the upper respiratory tract specimens (all P<0.001). Weakened underlying immunity is a correlative factor for long-term novel coronavirus nucleic acid positivity, and long-term positive novel coronavirus nucleic acid in severe patients indicates high risk of death. The nucleic acid of the lower respiratory tract specimen turned negative later than the upper respiratory tract specimen.

The value of multimodal magnetic resonance imaging in breast cancer and its correlation with pathological features and prognosis.

OBJECTIVE: This study aimed to explore the diagnostic value of multimodal magnetic resonance imaging (MRI) in breast cancer (BC) and its correlation with pathological features of the disease. PATIENTS AND METHODS: Clinical data of 85 BC patients (malignant group) and 85 patients with benign breast diseases (benign group), admitted to 3201 Hospital of Xi'an Jiaotong University Health Science Center from May 2020 to May 2022, were retrospectively collected. Both groups underwent multimodal MRI examinations. We compared the differences in multimodal MRI examination parameters between the groups, as well as between patients with different pathological characteristics and prognoses in the malignant group. The correlation between multimodal MRI examination parameters and pathological features of BC was analyzed. RESULTS: The apparent diffusion coefficient (ADC) of the malignant group was lower than that of the benign group, while the extravascular extracellular volume fraction (Ve), reaction rate constant (Kep), and volume transfer constant (Ktrans) of the malignant group were higher compared to the benign group (p<0.05). In the malignant group, patients with stage III+IV disease, lymph node metastases, and low differentiation had lower ADC values, and higher Ve, Ktrans, and Kep compared to patients with stage I+II disease, no lymph node metastasis, and medium to high differentiation (p<0.05). ADC value negatively correlated with the stage of the disease, lymph node metastases but positively correlated with the degree of differentiation (p<0.05). Ve, Ktrans, and Kep positively correlated with the stage of the disease and lymph node metastasis, and negatively correlated with the degree of differentiation (p<0.05). ADC value of patients with poor prognosis was lower, while Ve, Ktrans, and Kep were higher compared to patients with good prognosis (p<0.05). The Receiver operating characteristic (ROC) analysis showed that ADC, Ve, Ktrans, and Kep have certain predictive values for the poor prognosis of BC patients (p<0.05). CONCLUSIONS: Multimodal MRI examination detected obvious differences in the examination parameters of BC patients, and the increase or decrease in these parameters is closely correlated with the pathological characteristics and prognosis of the disease. Multimodal MRI examination can be used for pathological evaluation and prognosis prediction in BC patients.

[Guizhi Fuling Capsule inhibits migration and induces apoptosis of human ovarian cancer cells by regulating the NF-κB signaling pathway].

OBJECTIVE: To study the inhibitory effect of Guizhi Fuling Capsule (GFC) on migration of human ovarian cancer cells and explore the possible mechanism. METHODS: Sixty Wistar rats were randomized into 4 groups for daily gavage of saline or 4, 8, or 16 g/kg GFC suspension for 5 days to prepare blank and low-, medium- and high-dose GFC-medicated sera. Cisplatinresistant ovarian cancer SKOV3/DDP cells were treated with these sera with nuclear factor-κB (NF-κB) inhibitor SN50 as the positive control, and the changes in migration ability and apoptosis of the cells were examined using scratch assay and flow cytometry, respectively; the changes in the mRNA and protein expressions of CDH1, CDH2, caspase 3 and NF- κB were detected using RT-qPCR and Western blotting. ATAC-seq was used to analyze the changes in expressions of CDH1, CDH2, caspase 3 and NF-κB genes in the open chromatin. RESULTS: Treatment with GFC-medicated sera dose-dependently inhibited the migration (P < 0.05), increased apoptosis (P < 0.01), inhibited CDH2 and NF-κB mRNA expression (P < 0.05), and enhanced caspase 3 and CDH1 mRNA expressions (P < 0.01) in SKOV3/DDP cells. The effects of high-dose GFC-medicated serum were comparable to those of SN50 (P>0.05), but its effect for enhancing DH1 protein expression was weaker than that of SN50 (P < 0.01). GFC-medicated sera significantly lowered the expressions of NF-κB and CDH2 and increased CDH1 expression in the open chromatin without obviously affecting caspase 3 expression. CONCLUSION: GFC- medicated sera inhibits the migration ability of SKOV3/DDP cells possibly by promoting cell apoptosis and caspase 3 and CDH1 expressions, inhibiting CDH2 and NF-κB expressions, and regulating the expressions of NF-κB, CDH2 and CDH1 in the open chromatin.

[Effect of TFF3 on tight junction protein in eosinophilic chronic sinusitis and its related mechanism].

Objective: To study the effect of trefoil factor family (TFF) 3 on the expression of tight junctions (TJs) in the nasal mucosa epithelium of eosinophilic chronic rhinosinusitis (eCRS) and its mechanism. Methods: From September to December 2020, eligible patients from the Department of Otorhinolaryngology of the First Affiliated Hospital of Nanchang University were recruited, including 11 control patients and 37 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), from whom nasal mucosa and nasal polyp tissue samples were collected. Immunohistochemistry (IHC) was used to detect the localization and expression intensity of TFFs (TFF1, TFF2 and TFF3) and TJs (occudin, claudin-1 and ZO-1) in nasal mucosa. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were used to detect the mRNA and protein expression. A cell model of tight junction injury in human nasal epithelial cells (HNECs) through stimulation with interleukin (IL)-13 was also established. The optimal modeling concentration and time for HNECs were determined, which were subsequently treated with TFF3 and/or a phosphoinositide 3-kinase (PI3K)-specific inhibitor (LY294002). Finally, RT-qPCR and WB were used to assess the effects of TFF3 on tight junctions and the PI3K/serine/threonine kinase (Akt) signaling pathway. Data were analyzed statistically using GraphPad Prism 7 software. Results: IHC results showed that the expression of TFF1 and TFF3 in nasal mucosa of eCRS group was significantly higher than that of control group (t=4.62, P=0.002; t=5.89, P<0.001), respectively, mainly expressed in goblet cell. The expression of occludin, claudin-1 and ZO-1 in the nasal mucosa of the eCRS group was lower than that of the control group (occludin t=3.98, P=0.019; claudin-1 t=5.15, P=0.002; ZO-1 t=5.42, P=0.001), respectively. WB results showed that the expression of TFF3 in non-eosinophilic chronic sinusitis (Non-eCRS) group and eCRS group was higher than that in the control group (t=3.62, P=0.036; t=5.93, P<0.001). The expression of occludin, claudin-1 and ZO-1 in eCRS group was lower than that in the control group (occludin t=5.14, P=0.002; claudin-1 t=6.35, P<0.001; ZO-1 t=6.64, P<0.001), respectively. The RT-qPCR results showed that compared with the control group, the levels of TFF1 and TFF3 mRNA were increased in the nasal mucosal epithelium of the Non-eCRS and eCRS groups (TFF1 t=3.98, P=0.046, t=4.89, P=0.002; TFF3 t=3.50, P=0.044, t=6.78, P<0.001). There was no statistically significant difference in TFF2 mRNA levels between the Non-eCRS and eCRS groups (t=1.34, P=0.061; t=3.37, P=0.055). Compared with the control group, Non-eCRS and eCRS groups showed a decrease in the mRNA levels of occludin, claudin-1 and ZO-1 (occludin t=4.27, P=0.011, t=5.61, P=0.007; claudin-1 t=3.62, P=0.036, t=6.80, P<0.001; ZO-1 t=3.47, P=0.047, t=7.86, P<0.001). The mRNA levels of TFF3 and TJs in eCRS nasal mucosa tissue showed a moderate positive correlation (occludin r=0.661, claudin-1 r=0.614, ZO-1 r=0.548, all P<0.001); TFF1 showed a low degree of positive correlation with the expression of occludin, claudin-1 and ZO-1 (occludin r=0.467, P=0.040; claudin-1 r=0.362, P=0.012; ZO-1 r=0.425, P=0.025). The establishment of cell models showed that compared with normal HNECs, the mRNA expression of TFF3 was most significantly increased at a concentration of 50 ng/ml stimulated by IL-13 (t=3.72, P=0.013); The mRNA expression of occludin, claudin-1 and ZO-1 decreased (occludin t=3.18, P=0.031; claudin-1 t=3.86, P=0.010; ZO-1 t=5.16, P=0.002). The expression of TFF3 mRNA increased most significantly after 15 hours of IL-13 stimulation (t=3.14, P=0.034); The mRNA expression of occludin, claudin-1 and ZO-1 decreased (occludin t=3.97, P=0.010; claudin-1 t=4.78, P=0.004; ZO-1 t=5.16, P=0.004). TJs damage model could be established by treating HNECs with 50 ng/ml IL-13 for 15 hours. Intervention experiments showed that compared with the IL-13 group, the IL-13+TFF3 group showed an increase in TJs mRNA expression (occludin t=6.10, P=0.009; claudin-1 t=5.90, P=0.013; ZO-1 t=9.44, P=0.007). Compared with the IL-13 group, the expression of TJs protein in the IL-13+TFF3 group increased (occludin t=3.23, P=0.013; claudin-1 t=9.40, P=0.017; ZO-1 t=2.23, P=0.032); The expression of TJs protein decreased in the IL-13+TFF3+LY294002 group (occludin t=4.73, claudin-1 t=8.77, ZO-1 t=3.51, all P<0.001). Compared with the IL-13+TFF3 group, the IL-3+TFF3+LY294002 group showed a decrease in PI3K and p-Akt/Akt protein expression (PI3K t=13.29, p-Akt/Akt t=10.30, all P<0.001). The increased mRNA and protein expression of occludin, claudin-1 and ZO-1 induced by TFF3 were also inhibited by LY294002. Conclusion: TFF3 can up-regulate the expression of occludin, claudin-1, and ZO-1 through PI3K/Akt pathway, and has a certain protective effect on the nasal mucosal epithelial barrier, providing a new idea for treating eCRS.

[Evaluation effect of COMPERA 2.0 risk assessment model on prognosis of Chinese patients with pulmonary arterial hypertension].

Objectives: To clarify the evaluation effect of COMPERA 2.0 risk assessment model on prognosis of pulmonary arterial hypertension (PAH) in China. Methods: Patients with newly diagnosed PAH admitted in Fuwai hospital between April 2019 and March 2022 were enrolled retrospectively and divided in low, intermediate-low, intermediate-high and high strata by scores of COMPERA 2.0 risk assessment model. All the patients were followed up by clinic or telephone. The primary endpoint was defined as a composite of all-cause mortality, exacerbated heart failure and aggravated symptoms. Kaplan-Meier analysis and log-rank trend test were used to determine the risk of endpoints among the 4 groups. Multivariate Cox proportional hazards regression were used to analyze the association between COMPERA 2.0 scores and prognosis in patients with PAH. Results: A total of 951 patients with PAH were enrolled in this study. The age [M (Q1, Q3)] of the patients was 35 (28, 47) years, of which 706 cases (74.2%) were females. A total of 328 cases (34.5%) were assigned in low strata, 264 cases (27.8%) in intermediate-low strata, 193 cases (20.3%) in intermediate-high strata, and 166 cases (17.5%) in high strata. During the duration [M (Q1, Q3)] of follow-up after discharge of 1.8 (1.0, 2.8) years, the primary endpoint was occurred in 12.8% (42/328), 21.2% (56/264), 28.5% (55/193) and 42.8% (71/166) of low, intermediate-low, intermediate-high and high strata, respectively. The rates of primary endpoint were significantly increased with strata rising (P<0.001). Multivariate Cox proportional hazards regression showed that COMPERA 2.0 risk scores were associated with the primary endpoints in PAH patients (HR=1.801, 95%CI: 1.254-2.588, P=0.001) after adjusting confounders. Conclusion: COMPERA 2.0 risk assessment model is a simple and effective tool for evaluating the prognosis of newly diagnosed PAH patients in China.

[Comparative analysis of clinical diagnosis and treatment guidelines for drug-induced liver injury at home and abroad].

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.

Release of Interface Confined Water Significantly Improves Dentin Bonding.

Water residue and replacement difficulty cause insufficient adhesive infiltration in demineralized dentin matrix (DDM), which produces a defective hybrid layer and thus a bonding durability problem, severely plaguing adhesive dentistry for decades. In this study, we propose that the unique properties of a highly hydrated interface of the porous DDM can give rise to 1 new type of interface, confined liquid water, which accounts for most of the residue water and may be the main cause of insufficient infiltration. To prove our hypothesis, 3 metal ions with increasing binding affinity and complex stability (Na+, Ca2+, and Cu2+) were introduced respectively to coordinate negatively charged groups such as -PO43-, -COO- abundant in the DDM interface. Strong chelation of Ca2+ and Cu2+ rapidly released the confined water, significantly improving penetration of hydrophobic adhesive monomers, while Na+ had little effect. A significant decrease of defects in the hybrid layer and a much decreased modulus gap between the hybrid layer and the adhesive layer greatly optimized the microstructure and micromechanical properties of the tooth-resin bonding interface, thus improving the effectiveness and durability of dentin bonding substantially. This study paves the way for a solution to the core scientific issue of contemporary adhesive dentistry: water residue and replacement in dentin bonding, both theoretically and practically.

[Epidemiological characteristics of a 2019-nCoV outbreak caused by Omicron variant BF.7 in Shenzhen].

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.

[Comparison of three different measurement methods to determine resting energy expenditure in patients with decompensated hepatitis B cirrhosis].

Objective: To compare the differences to determine resting energy expenditure (REE) measured with indirect calorimetry and REE predicted by formula method and body composition analyzer in patients with decompensated hepatitis B cirrhosis, so as to provide theoretical guidance for the implementation of precision nutrition intervention. Methods: Patients with decompensated hepatitis B cirrhosis who were admitted to Henan Provincial People's Hospital from April 2020 to December 2020 were collected. REE was determined by the body composition analyzer and the H-B formula method. Results: were analyzed and compared to REE measured by the metabolic cart. Results A total of 57 cases with liver cirrhosis were included in this study. Among them, 42 were male, aged (47.93 ± 8.62) years, and 15 were female aged (57.20 ± 11.34) years. REE measured value in males was (1 808.14 ± 201.47) kcal/d, compared with the results calculated by the H-B formula method and the measured result of body composition, and the difference was statistically significant (P = 0.002 and 0.003, respectively). REE measured value in females was (1 496.60 ± 131.28) kcal/d, compared with the results calculated by the H-B formula method and the measured result of body composition, and the difference was statistically significant (P = 0.016 and 0.004, respectively). REE measured with the metabolic cart had correlation with age and area of visceral fat in men (P = 0.021) and women (P = 0.037). Conclusion: Metabolic cart use will be more accurate to obtain resting energy expenditure in patients with decompensated hepatitis B cirrhosis. Body composition analyzer and formula method may underestimate REE predictions. Simultaneously, it is suggested that the effect of age on REE in H-B formula should be fully considered for male patients, while the area of visceral fat may have a certain impact on the interpretation of REE in female patients.

[Preliminary analysis of seasonal pollen allergens of allergic rhinitis in a hospital of Nanchang City].

The study was aimed to analyze the seasonal pollen allergen spectrum of patients with allergic rhinitis (AR) in Nanchang city, and to provide evidence for improving the clinical diagnosis, treatment, prevention and epidemiology of seasonal AR. A retrospective analysis was conducted on the results of skin prick test (SPT) among 1 752 patients with AR in outpatient at Department of Otolaryngology, the First Affiliated Hospital of Nanchang University from September 2020 to August 2021 (a total of 1 069 males and 683 females, age ranged from 2 to 84 years old). SPSS 22.0 software was used to analyze the positive rates of main allergens and their differences in gender, age, and month of visit. Differences among groups were compared by student t test, Wilcox rank sum test, or χ2 test. The results showed that among 1 752 SPT-positive patients, the number of simple seasonal AR and the number of perennial combined seasonal AR were 102 (5.82%) and 281 (16.04%), respectively. There was no significant difference between male and female patients in positive seasonal pollen allergens (χ2=2.181, P>0.05), but the positive rate of indoor seasonal pollen allergens in males was higher than that in females (χ2=7.901, P<0.05). The seasonal pollen allergens ranking top 5 of the positive rates were willow (6.62%, 116/1 752), humulus scandens (5.71%, 100/1 752), rape (5.54%, 97/1 752), grey pigweed (4.62%, 81/1 752) and birch (3.60%, 63/1 752). The positive rates of indoor and seasonal pollen allergens increased first and then decreased in different age groups, and the highest positive rates of seasonal pollen allergens were in the age group of 31-40 years old, with statistical significance compared with other groups (χ2=61.269, P<0.05). The seasonal allergen positive rate showed two peaks in time: March to May and September to November. The positive rate of pollen in spring was 60.27% (132/219), which was significantly higher than that in autumn (39.73%,87/219) (χ2=9.247, P<0.05). The positive rate of pollen combination in spring and autumn was 68.29% (112/164), which was significantly higher than that in spring and autumn alone (18.9%,31/164) and (12.8%, 21/164) (χ2=14.731, P<0.05). In summary, pollen allergy in Nanchang City cannot be ignored, accounting for more than 20% of the total number of AR. The incidence of seasonal AR in Nanchang City showed two peaks (March to May and September to November). The common allergens for seasonal AR in Nanchang City were willow, humulus scandens, rape, grey chenopods and birch.

[Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.

Effect of ventilation mode on postoperative pulmonary complications following lung resection surgery: a randomised controlled trial.

The effect of intra-operative mechanical ventilation modes on pulmonary outcomes after thoracic surgery with one-lung ventilation has not been well established. We evaluated the impact of three common ventilation modes on postoperative pulmonary complications in patients undergoing lung resection surgery. In this two-centre randomised controlled trial, 1224 adults scheduled for lung resection surgery with one-lung ventilation were randomised to one of three groups: volume-controlled ventilation; pressure-controlled ventilation; and pressure-control with volume guaranteed ventilation. Enhanced recovery after surgery pathways and lung-protective ventilation protocols were implemented in all groups. The primary outcome was a composite of postoperative pulmonary complications within the first seven postoperative days. The outcome occurred in 270 (22%), with 87 (21%) in the volume control group, 89 (22%) in the pressure control group and 94 (23%) in the pressure-control with volume guaranteed group (p = 0.831). The secondary outcomes also did not differ across study groups. In patients undergoing lung resection surgery with one-lung ventilation, the choice of ventilation mode did not influence the risk of developing postoperative pulmonary complications. This is the first randomised controlled trial examining the effect of three ventilation modes on pulmonary outcomes in patients undergoing lung resection surgery.

[Correlation between heart rate index, SBPpeak-to-SBPrest ratio and peak oxygen consumption in patients with chronic heart failure].

Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO2) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO2, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO2 and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO2 showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO2 showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO2 higher than female(r=-0.229, P<0.001); PeakVO2 of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO2 (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO2(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO2(t=-5.43, -0.31, respectively, all P<0.05). PeakVO2 of male was higher than female(t=-6.03, P<0.05), and peakVO2 of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R2=0.29) could be constructed: peakVO2=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO2. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.

Psoriasis may increase the risk of lung cancer: a two-sample Mendelian randomization study.

BACKGROUND: Although many studies have indicated that Psoriasis (PsO) could contribute to the risk of lung cancer, no study has reported a clear causal association between them. Our aim was to explore the potential causal association between PsO and the lung cancer risk using Mendelian randomization (MR) design. METHODS: To explore a causal association between the PsO and lung cancer, we used large-scale genetic summary data from genome-wide association study (GWAS), including PsO (n = 337 159) and lung cancer (n = 361 586), based on previous observational studies. Our main analyses were conducted by inverse-variance weighted (IVW) method with random-effects model, with a complementary with the other two analyses: weighted median method and MR-Egger approach. RESULTS: The results of IVW methods demonstrated that genetically predicted PsO was significantly associated with higher odds of lung cancer, with an odds ratio (OR) of 1.06 (95%CI, 1.01-1.12; P = 0.02). Weighted median method and MR-Egger regression also demonstrated directionally similar results (All P < 0.05). In addition, both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between PsO and lung cancer. CONCLUSIONS: Our study provided potential evidence between genetically predicted PsO and lung cancer, which suggested that enhanced screening for lung cancer allows early detection of lung cancer.

[Reconstruction of facial skin defects by the V-Y subcutaneous pedicle flap].

Objective: To investigate the method and efficacy of reconstruction of facial skin defects after removing the lesions by applying the V-Y subcutaneous pedicle flap. Methods: A retrospective analysis was performed on 23 patients with facial reconstruction by using V-Y subcutaneous pedicle flap in the Otolaryngology Department of Guangdong Integrated Traditional Chinese and Western Medicine Hospital from March 2012 to April 2021. Patient ages ranged from 45 to 85 years old, with a mean age of 66.5 years (14 males and 9 females). The facial lesion sites included cheek in 12 cases (nearly lower eyelid in 4 cases), nose in 4 cases, lips in 3 cases, temporal in 2 cases and mental region in 2 cases. The initial pathology included malignant tumors (7 cases of basal cell carcinoma (BCC), 2 cases of squamous cell carcinoma(SCC), and 1 case of malignant melanoma) and benign lesions (7 cases of keratoderma, 3 cases of intradermal nevus, 1 case of pilomatricoma, 1 case of cutaneous mixed tumor and 1 case of epidermal cyst). The V-Y subcutaneous facial pedicled flaps were designed reasonably after the facial lesions were excised. The advantages of blood supply, survival rate and adverse events of the flap were analyzed Chi-square test was used to compare the observation results of different types of patients. Results: The primary focus of 23 patients was excised surgically, and intraoperative frozen-section examinations were performed for obtaining margins negative as far as possible. One positive margin was still found in 1 patient after multiple resection in our group. The defect sizes were 14 mm×12 mm-59 mm×54 mm. All the flaps survived. The adverse events were slight necrosis of the epidermis at the junction or vicinity of the three arms of "Y" shaped in 4 cases, but the wounds finally recovered by wet compress and dressing change. There were no significant differences in the incidences of adverse events between double and single pedicle flaps (4/19 vs. 0/4), between benign and malignant lesions (4/13 vs. 0/10), and between patients with and without underlying diseases (1/6 vs. 3/17) (χ2 values were 0.98, 3.56, 0.01, respectively, all P>0.05). There were no other major complications such as dehiscence, hematoma, eyelid ectropion and lip deformation. The patients with benign lesions were followed-up at least for 3 months, while those with malignant tumors were followed-up for 6-36 months postoperatively, without recurrence. Conclusions: V-Y subcutaneous facial pedicled skin flap may be a "no-easy-necrotic" local flap in the repair of small and medium-sized facial defects.

[Lipid metabolism in idiopathic pulmonary fibrosis].

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology, which was characterized by irreversible lung function decrease and high mortality. Up till now, only two drugs, i.e. Pirfenidone and Nintedanib,have been approved by Food and Drug Administration (FDA) for therapy of IPF, and the treatment is less effective. Therefore, it is urgent to develop new therapeutic drugs. In recent years, studies had paid attention to lipid metabolism in IPF. In this review, we discussed recent major advances of lipid metabolism, biomarkers and clinical trials in IPF.

[Research advances in the treatment of liver failure with mesenchymal stem cell-derived exosomes].

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.