Polygenic Risk Score Reveals Genetic Heterogeneity of Alzheimer's Disease between the Chinese and European Populations.

BACKGROUND: The polygenic risk score (PRS) aggregates the effects of numerous genetic variants associated with a condition across the human genome and may help to predict late-onset Alzheimer's disease (LOAD). Most of the current PRS studies on Alzheimer's disease (AD) have been conducted in Caucasian ancestry populations, while it is less studied in Chinese. OBJECTIVE: To establish and examine the validity of Chinese PRS, and explore its racial heterogeneity. DESIGN: We constructed a PRS using both discovery (N = 2012) and independent validation samples (N = 1008) from Chinese population. The associations between PRS and age at onset of LOAD or cerebrospinal fluid (CSF) biomarkers were assessed. We also replicated the PRS in an independent replication cohort with CSF data and constructed an alternative PRS using European weights. SETTING: Multi-center genetics study. PARTICIPANTS: A total of 3020 subjects were included in the study. MEASUREMENTS: PRS was calculated using genome-wide association studies data and evaluated the performance alone (PRSnoAPOE) and with other predictors (full model: LOAD ~ PRSnoAPOE + APOE+ sex + age) by measuring the area under the receiver operating curve (AUC). RESULTS: PRS of the full model achieved the highest AUC of 84.0% (95% CI = 81.4-86.5) with pT< 0.5, compared with the model containing APOE alone (61.0%). The AUC of PRS with pT<5e-8 was 77.8% in the PRSnoAPOE model, 81.5% in the full model, and only ranged from 67.5% to 75.1% in the PRS with the European weights model. A higher PRS was significantly associated with an earlier age at onset (P <0.001). The PRS also performed well in the replication cohort of the full model (AUC=83.1%, 95% CI = 74.3-92.0). The CSF biomarkers of Aß42 and the ratio of Aß42/Aß40 were significantly inversely associated with the PRS, while p-Tau181 showed a positive association. CONCLUSIONS: This finding suggests that PRS reveal genetic heterogeneity and higher prediction accuracy of the PRS for AD can be achieved using a base dataset and validation within the same ethnicity. The effective PRS model has the clinical potential to predict individuals at risk of developing LOAD at a given age and with abnormal levels of CSF biomarkers in the Chinese population.

Association between gestational cardiovascular health in the first trimester and pregnancy outcomes in the China birth cohort.

OBJECTIVES: To determine whether gestational cardiovascular health (CVH) during the first trimester is associated with a risk of adverse pregnancy outcomes. STUDY DESIGN: A multicentre prospective cohort; part of the China birth cohort study. METHODS: Pregnant women were recruited at 6-13+6 gestation weeks and followed to delivery to identify pregnancy outcomes. Gestational CVH in the first trimester was assessed using five CVH metrics: body mass index, smoking, blood pressure, glucose, and lipids. Multilevel modified Poisson regression models calculated the relative risks (RRs) and 95% confidence intervals (95% CIs) of gestational CVH for adverse pregnancy outcomes. RESULTS: Among 56,852 pregnant women, the mean score for gestational CVH during the first trimester was 9.1. Adjusting for confounding factors, each 1-point decrease in the total gestational CVH score significantly increased the risk of hypertensive disorders of pregnancy (RR = 1.682, 95% CI: 1.624-1.743), gestational diabetes mellitus (RR = 1.405, 95% CI: 1.384-1.426), preterm birth (RR = 1.184, 95% CI: 1.174-1.195), large for gestational age (RR = 1.224, 95% CI: 1.199-1.250), caesarean delivery (RR = 1.073, 95% CI: 1.049-1.097), and low Apgar score (RR = 1.131, 95% CI: 1.003-1.277) significantly increased. Meanwhile, the risk of small for gestational age decreased (SGA; RR = 0.922, 95% CI: 0.898-0.946). Worsened CVH categories significantly increased the risk of adverse pregnancy outcomes, excluding SGA. CONCLUSIONS: Poor gestational CVH in the first trimester significantly increases the risk of adverse pregnancy outcomes, emphasising the need for early improvement in gestational CVH.

Classification of breast edema on T2-weighted imaging for predicting sentinel lymph node metastasis and biological behavior in breast cancer.

OBJECTIVE: To determine whether preoperative classification of breast edema on T2-weighted imaging (T2WI) is useful for predicting sentinel lymph node (SLN) metastasis and biological behavior in patients with early-stage breast cancer. METHODS: This retrospective study involved 341 women with breast cancer who underwent breast MRI from January 2019 to March 2022. Breast edema was scored on a scale of 1-4 on T2WI (1, no edema; 2, peritumoral edema; 3, prepectoral edema; and 4, subcutaneous edema). A logistic regression model was employed for univariate and multivariate analyses. A clinicopathological model was established using independent influencing factors identified in the multivariate analyses, excluding breast edema score (BES). Subsequently, BES was incorporated into this model to establish a combined BES model. The AUC and Delong test were used to examine the additional predictive value of the BES. RESULTS: Logistic regression analysis showed that breast edema was an independent risk factor for SLN metastasis. The combined BES model significantly improved the predictive performance of SLN metastasis compared with the clinicopathological model alone (AUC, 0.77 vs. 0.71; p=0.005). In addition, the BES was significantly positively correlated with the tumor diameter (p<0.001), histologic grade (p=0.001), Ki-67 index (p<0.001), and non-luminal subtypes (p<0.001). CONCLUSION: The BES on T2WI is useful for predicting SLN metastasis. A higher grade of breast edema is associated with breast cancer aggressiveness and increases the probability of SLN metastasis.

Effects of fermented cottonseed meal inclusions on growth performance, serum biochemical parameters and hepatic lipid metabolism of geese during 28-70 d of age.

The aim of this study was to investigate the effects of solid-state fermented cottonseed meal (FCSM) inclusion levels on the growth performance, serum biochemical parameters and hepatic lipid metabolism in geese from 28 to 70 d of age. A total of 288 twenty-eight-d-old male geese were randomly divided into 4 treatments with FCSM levels of 0, 5, 15 and 25% including 0, 22.74, 67.33, 111.27 mg FG/kg diet, respectively. Each treatment contained 6 replicates and 12 birds per replicate. Treatments of FCSM inclusions from 0 to 25% had no effect on growth rate and feed intake in geese during d 28 to 70. The F/G ratio was increased (P < 0.05) in geese fed the diet with 25% FCSM compared with birds fed the diet with 0% FCSM. Treatment with 25% FCSM levels had no effect on the contents of TC, TG, HDL-C, LDL-C, but increased (P < 0.05) AST and ALT activities in serum of geese at d 70. Treatment with 25% FCSM increased the contents of FG, HDL-C, TC, C18:2n6, C20:4n6 and PUFA and decreased (P < 0.05) the contents of NEFA, SFA, MUFA in liver compared with treatment of 0% FCSM inclusion. Additionally, treatment with 25% FCSM decreased (P < 0.05) the PPARα, AMPK, and LXR mRNA expression related to lipid deposition, and increased (P < 0.05) PPARγ and ACC mRNA expression related to lipolysis in liver compared with birds fed the diet with 0% FCSM. Overall, treatment with 0 to 15% FCSM (<=67.33 mg FG/kg diet) had no adverse effects on the growth performance and lipid metabolism of geese. However, treatment fed 25% FCSM (111.27 mg FG/kg diet) decreased feed efficiency and promoted hepatic lipid deposition associated with the alteration of related gene expression in geese at 28 to 70 d of age.

Effect of internal phase particle size on properties of site mixed emulsion explosive at plateau environment.

To study the effect of internal particle size on the microstructure properties and thermal decomposition characteristics of site mixed emulsion explosive at different altitudes. Site mixed emulsion explosive was prepared with different shear rate. The particle size, viscosity, sensitized bubbles, detonation velocity and peak pressure of the emulsion explosive were tested after stored at different simulated altitudes. The thermal decomposition characteristics of emulsion matrix prepared at three different rotational speeds were measured by thermogravimetric analyzer and kinetic analysis was performed by non-isothermal model Kissinger-Akah-Sunose (KAS) method. The results show that with the increase in altitude, the internal phase size showed a trend of first increasing and then decreasing, and the number of sensitized bubbles within the emulsion explosive decreases. At an altitude of 0 m, the detonation velocity and peak overpressure of the emulsion explosive prepared by 1600 r min-1 increased 4.78% and 29.09%, respectively compared with 1200 r min-1, and at an altitude of 4500 m, the detonation velocity increased 11.87%, the peak overpressure increased 43.98%. The thermal decomposition activation energy of the emulsion matrix at 1600 r min-1 increased 13.14% compared to 1200 r min-1. It shows that in the production of site mixed emulsion explosive at high altitude, reducing the particle size of the internal phase of emulsion explosives in a certain range can effectively improve the performance of emulsion explosives.

Improving image quality of triple-low-protocol renal artery CT angiography with deep-learning image reconstruction: a comparative study with standard-dose single-energy and dual-energy CT with adaptive statistical iterative reconstruction.

AIM: To investigate the improvement in image quality of triple-low-protocol (low radiation, low contrast medium dose, low injection speed) renal artery computed tomography (CT) angiography (RACTA) using deep-learning image reconstruction (DLIR), in comparison with standard-dose single- and dual-energy CT (DECT) using adaptive statistical iterative reconstruction-Veo (ASIR-V) algorithm. MATERIALS AND METHODS: Ninety patients for RACTA were divided into different groups: standard-dose single-energy CT (S group) using ASIR-V at 60% strength (60%ASIR-V), DECT (DE group) with 60%ASIR-V including virtual monochromatic images at 40 keV (DE40 group) and 70 keV (DE70 group), and the triple-low protocol single-energy CT (L group) with DLIR at high level (DLIR-H). The effective dose (ED), contrast medium dose, injection speed, standard deviation (SD), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of abdominal aorta (AA), and left/right renal artery (LRA, RRA), and subjective scores were compared among the different groups. RESULTS: The L group significantly reduced ED by 37.6% and 31.2%, contrast medium dose by 33.9% and 30.5%, and injection speed by 30% and 30%, respectively, compared to the S and DE groups. The L group had the lowest SD values for all arteries compared to the other groups (p<0.001). The SNR of RRA and LRA in the L group, and the CNR of all arteries in the DE40 group had highest value compared to others (p<0.05). The L group had the best comprehensive score with good consistency (p<0.05). CONCLUSIONS: The triple-low protocol RACTA with DLIR-H significantly reduces the ED, contrast medium doses, and injection speed, while providing good comprehensive image quality.

[High-risk sexual behaviors of HIV/AIDS and related factors in young students in Guangzhou].

Objective: To explore high-risk sexual behaviors of HIV/AIDS and related factors in young students in Guangzhou. Methods: A cross-sectional survey was conducted in 5 different types of Guangzhou colleges by convenience sampling with minimum number of classes per grade and 600 samples per school from September to November 2021. The R 4.2.2 software was used to consolidate databases. Simultaneously, a logistic regression model and a decision tree algorithm model, stratifying by whether sexual behaviors had occurred before, were constructed. In each layer, the prediction performance of the two models was evaluated through area under receiver operating characteristic and the confusion matrix, and then the model with high prediction performance was retained. Results: A total of 7 346 students were surveyed. The proportion of the respondents reporting sexual experience were 9.08% (667/7 346), in whom 26.24% (175/667) had risky sexual activity in the past year. The decision tree algorithm model performs well in predicting whether high-risk sexual behaviors have occurred in the past year. When the complexity parameter value is 0.018, and nsplit reaches 4, which means there are 5 leaf nodes in the model, the cross error of the tree will be the smallest. The first best grouping variable in the decision tree was whether to use condoms throughout the first sexual behavior. If condoms were used at their sexual debut, but homosexual practices have occurred in the past year, the probability of risky sexual behavior will increase. If homosexual practices have not occurred in the past year, but the age of sexual debut was below 18 years old while the period of HIV education was after high school, the probability of risk sexual behavior will also increase. Conclusions: AIDS-related risky behaviors of young students still deserved attention. The experience of sexual debut and whether AIDS-related health education has been received before the sexual debut were significant predictors for the occurrence of high-risk sexual behavior. The decision tree algorithm model has particular applicability for predicting and screening potential risk populations.

Elevated MIF identified by multiple cytokine analyses facilitates macrophage M2 polarization contributing to postoperative recurrence in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by tissue heterogeneity and high postoperative recurrence risk. This study aims to employ cytokine analyses to identify serum biomarkers associated with postoperative CRSwNP recurrence and elucidate underlying recurrent mechanisms. METHODS: A prospective cohort study was conducted on CRSwNP patients undergoing functional endoscopic sinus surgery. Serum and tissue samples were collected and analyzed for multiple cytokines. Participants were followed for 3 years and categorized into recurrent and non-recurrent groups. Cytokine profiles were compared, and potential markers for recurrence were further assessed. Macrophage migration inhibitory factor (MIF) expression in macrophages was modulated, and their polarization and cytokine secretion were assessed. RESULTS: In the discovery cohort (21 recurrent and 40 non-recurrent patients), circulating cytokine profiles differed significantly, with 8 cytokines showing differential expression between the two groups. Among them, serum eotaxin, MIF, RANTES, and TRAIL exhibited promise in predicting recurrence. In the validation cohort (24 recurrent and 44 non-recurrent patients), serum eotaxin, MIF, and TRAIL levels were higher in recurrent cases. Tissue MIF was elevated in recurrent cases and had a strong predictive value for recurrence. Moreover, tissue MIF was co-expressed with CD206 in recurrent cases. Mechanistically, MIF overexpression promoted macrophage M2 polarization and TGF-ß1, CCL-24, and MIF secretion, and MIF recombinant protein facilitated M2 polarization, and TGF-ß1 and CCL-24 production, contributing to CRSwNP recurrence. CONCLUSIONS: Serum-specific cytokine signatures were associated with postoperative recurrence risk in CRSwNP. Elevated MIF enhanced macrophage M2 polarization and cytokine secretion, contributing to the recurrent mechanisms of CRSwNP.

[Microwave ablation versus radiofrequency ablation for solid or predominantly solid benign thyroid nodules: a randomized controlled clinical trial].

Objective: To compare the short-term efficacy and the safety of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of benign thyroid nodules (BTNs). Methods: This prospective randomized controlled trial, performed from December 2019 to September 2021, included 36 patients with solid or predominantly solid BTNs who met the eligibility criteria and provided written informed consent at the Nanjing sub-center (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine). Patients were assigned to either the MWA group or the RFA group (18 patients in each group) at a ratio of 1∶1 using a block randomization design and allocation concealment using sealed envelope randomization. The independent-sample t-test and χ2 test were used to compare the volume reduction rates (VRRs), effective rates (VRRs≥50%), cosmetic scores, and complication rates at 1, 3, and 6 months after treatment between the two groups. Results: The clinical characteristics of the two groups of patients were comparable. After ablation, the nodule volume was significantly reduced in both groups. At 1, 3, and 6 months, there was no significant difference in the volume between the two groups (all P>0.05). At 3 months, the RFA group had a larger VRRs than that in the MWA group (62.08%±12.46% vs. 46.90%±23.16%, t=-2.45, P=0.021). However, at 1 and 6 months, no statistical significance was observed (both P>0.05). No significant difference was observed in the effective rates at the last follow-up (14/18 vs. 18/18, P=0.104). However, the RFA group had a lower cosmetic score than that in the MWA group (1.78±0.43 vs. 2.17±0.51, t=-2.47, P=0.019). There was no statistically significant difference in the complication rates between the two groups (all P>0.05). Conclusions: Both MWA and RFA were effective and safe treatments for BTNs, with no significant differences in short-term efficacy and safety. In addition, the RFA group showed slightly more favorable outcomes than the MWA group in terms of cosmetic improvement.

Intraosseous schwannoma of the mandible: new case series, literature update, and proposal of a classification.

Intraosseous schwannoma of the mandible is rare, with diagnostic and therapeutic challenges. The aims of this study were to report new cases of intraosseous schwannoma of the mandible and to propose a clinical classification, providing suggestions for treatment methods. The cases of 13 patients treated at the authors' hospital and 86 cases reported previously in the literature were reviewed. The most common clinical feature was facial swelling (60/93). The rate of cortical thinning or expansion was 44.8% (43/96); widening of the inferior alveolar nerve canal on radiographs was observed in 15 patients.

[Perception of HIV-related behavior and influencing factors among young students in Guangzhou].

Objective: To investigate the risk perception for risky behavior of HIV/AIDS infection among young students and to analyze the related influencing factors. Methods: A cross-sectional survey was conducted in 5 different types of Guangzhou colleges from September to November 2021, in which convenience sampling and a minimum number of classes per grade and 600 samples per school were used according to the national unity program. Disordered multi-classification logistic regression was used to construct a risk perception model and analyze influencing factors in different risk perception levels. Results: A total of 7 346 young students were surveyed, and most rated themselves at low risk of HIV/AIDS infections (90.58%, 6 654/7 346). A total of 89.10% (6 545/7 346) of subjects' perception of their HIV/AIDS infection risk was consistent with their risk behavior, while 10.90% (801/7 346) was inconsistent. Among those inconsistent subjects, 19.10% (153/801) showed underestimating their risk , while 80.90% (648/801) seen overestimating their risk. Disordered multi-classification logistic regression analysis showed that, after controlling for other factors, compared with the non-sexual group, respondents whose first sex age under 18 had a higher rate of underestimating their risk of infection (OR=129.39, 95%CI: 73.28-228.48), as well as a higher rate of overestimated their risk of infection (OR=1.76, 95%CI: 1.04-2.99). First sexual intercourse at age 18 or older was a risk factor for underestimating risk (OR=70.56, 95%CI: 42.72-116.53), but was not statistically associated with overestimating risk. Being female, other school type, non-heterosexual orientation, and self-rated HIV-related knowledge as fair or no knowledge were risk factors for overestimating risk but were not statistically associated with underestimating risk. Conclusions: Overall, young students in universities of Guangzhou have a good risk perception of HIV/AIDS infection. Individual factors, education factors and sexual experience will influence students' risk perception of HIV/AIDS infection. Raising the awareness rate of HIV/AIDS knowledge and delaying the age of first sexual intercourse will improve the risk perception ability of young students.

[Transcriptome sequencing for identification of the genes associated with restenosis of venous grafts in rabbits].

OBJECTIVE: To identify the genes associated with venous graft restenosis in rabbits using transcriptome sequencing. METHODS: Forty New Zealand rabbits were randomly divided into experimental group and control group, and in the experimental group, the left external jugular veins of the rabbits were engrafted to the left common carotid artery with continuous running suture; the rabbits in the control group received no operation. At 2 and 4 weeks after the operation, 10 rabbits from each group were euthanized and the venous grafts (in experimental group) or left external jugular vein (in control group) were harvested for measurement of the intima-media thickness using HE staining. RNA high-throughput sequencing (RNA-seq) was performed to identify the differentially expressed genes (DEGs) between the venous grafts and the control veins, and the biological functions of the DEGs were analyzed using GO and KEEG databases. RESULTS: In the experimental group, intima-media thickening with increased extracellular matrix and vascular smooth muscle cell proliferation occurred in the venous grafts at 2 weeks and aggravated at 4 weeks after the operation. RNA high-throughput sequencing identified 1583 up-regulated genes and 608 down-regulated genes in the venous grafts in the experimental group, and GO and KEGG analysis of the DEGs pinpointed 10 hub genes, namely CD4, ZAP70, SYK, CD28, PIK3CD, CXCR4, CCR5, ITK, CCL5 and BTK. CONCLUSION: CD4, ZAP70, SYK, CD28, PIK3CD, CXCR4, CCR5, ITK, CCL5 and BTK are probably the key genes associated with vein graft restenosis in rabbits.

[Application of stereoscopic unequal S-plasty for reconstuction of the congenital hypoplastic ear lobe cleft associated with soft tissue deficiency].

Objective: To explore the ideal way of using the stereoscopic unequal S-plasty in reconstruction of the congenital hypoplastic ear lobe cleft with soft tissue deficiency. Methods: Data of 10 patients with the congenital hypoplastic ear lobe cleft associated with soft tissue deficiency who were treated using the stereoscopic unequal S-plasty in the plastic cosmetic surgery of Xuzhou Central Hospital from Aug 2018 to Aug 2022 were retrospectively analyzed. Six patients were male, 4 were female. Their ages ranged from 6 years to 19 years old, with a mean age of 13 years. Lobe deficiency size ranged from 0.8 cm×0.5 cm to 1.2 cm×1.0 cm. Results: The post-operation flaps had no venous congestion, infection or necrosises. During 3 to 12 months of follow-up, the technique made the shape of the ear lobe smoother. The incisions left inconspicuous scars. The result was satisfactory in terms of matching the contralateral normal ear lobe in shape and symmetry. Doctors and patients were satisfied with the results. Conclusions: The stereoscopic unequal S-plasty is an effective way to correct the the severe congenital ear lobe deformity. The good result,simple manipulation and short operation time are the advantages of this method.

[The efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy in children with allergic rhinitis during treatment].

Objective: To evaluate the efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic rhinitis (AR) during treatment. Methods: A total of 283 children with AR diagnosed with definite dust mite allergy and completed 2 to 3 years of SCIT who attended the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, from August 2019 to October 2021 were included, including 205 males and 78 females, with a mean age of 10.8 years. The total nasal symptoms score (TNSS), symptom medication score (SMS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS) before and after 2 to 3 years' treatment were recorded, and the differences before and after treatment were compared. Adverse reactions during SCIT were recorded to evaluate its safety. SPSS 22.0 software was used for statistical analysis. Results: The overall effectiveness rate during SCIT in 283 children with AR was 89.4% (253/283). Compared with baseline, all symptom scores, medication scores and quality of life scores were significantly lower after 2 to 3 years of SCIT (all P<0.05). Further group comparisons showed positive efficacy in patients with different clinical characteristics, including age, gender, smoking status, family history of AR, symptom severity, mono-or poly-allergy, and second immunization, with no statistically significant differences between groups (all P>0.05). A total of 12 735 injections were administered during the SCIT, and a total of 213 (1.67%) injections of local adverse reactions occurred, mainly in the initial treatment phase, and the diameter of the local air mass was mostly 5 to 20 mm; 71 (0.56%) injections of systemic adverse reactions occurred, mainly in the initial treatment phase, and most of them were grade 1 reactions with no serious systemic adverse reaction such as shock. Conclusion: Standardized dust mite SCIT has a good safety profile and definite efficacy in treating AR children with different clinical characteristics. It can significantly improve all symptoms, reduce the use of symptomatic drugs and improve their quality of life.

Serum metabolomics identifies uric acid as a possible novel biomarker for predicting recurrence of chronic rhinosinusitis with nasal polyps.

BACKGROUND: Metabolomics has proven to be a valuable tool in gaining new insights into disease progression and prognosis, the specific metabolic alterations in the serum of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) patients remain unknown. This study aims to explore the serum metabolomic profiles of recurrent CRSwNP and identify potential predictive biomarkers. METHODS: A prospective, single-center study was conducted on CRSwNP patients prior to endoscopic sinus surgery. Serum samples were subjected to untargeted metabolomic profiling. Patients were followed up for over 2 years and categorized into recurrence and non-recurrence groups. Metabolite differences between the two groups were compared, and the identified differentially regulated metabolites were subsequently validated in a large clinical cohort. RESULTS: 67 CRSwNP patients completed the follow-up schedule, with 47 classified into the non-recurrent group and 20 into the recurrent group. Significant differences were found in the metabolomic profiles between both groups, and serum uric acid (SUA) showed promising predictive potential for postoperative recurrence in both positive and negative ion models. A validation cohort comprising 398 non-recurrent and 142 recurrent CRSwNP patients was recruited, and a significant elevation in SUA levels was observed in recurrent cases. Patients were stratified into tertiles based on the distribution of baseline SUA levels. Multivariate Cox regression analysis showed that higher tertiles of SUA were associated with an increased risk of CRSwNP recurrence compared to lower tertiles, even after adjusting for potential confounding factors. The receiver operating characteristic curve and Kaplan-Meier survival analysis highlighted that elevated SUA levels exhibited potential predictive values for postoperative recurrence. CONCLUSION: Serum metabolic signatures might predict postoperative recurrence in CRSwNP patients. Increased SUA concentrations were found to be associated with a higher risk of future postoperative recurrence in CRSwNP, independent of traditional risk factors.

[Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma].

OBJECTIVE: To explore the significance and feasibility of whole exon sequencing and immune related indexes in personalized precision treatment of oral squamous cell carcinoma (OSCC). METHODS: We retrospectively screened the patients who underwent surgery for oral cancer in Peking University Hospital of Stomatology and underwent genetic and immune biomarkers tests between January 2021 and June 2022. Combined with the clinicopathological characteristics of patients, potential targeted drugs and immunotherapy drugs were screened to evaluate the possibility of gene testing benefiting OSCC. The main evaluation indicators included the number of gene mutations, combined positive score (CPS), tumor mutation burden (TMB), microsatellite sequence status and human leukocyte antigen B (HLA-B) locus. Excel was used for statistical analysis. RESULTS: A total of 10 patients were enrolled and 9 were included in this study, including 6 males and 3 females, with an average age of (55.44±9.59) years. The tumor location was buccal (5 cases), tongue (3 cases) and gingival (1 case). The results of genetic testing showed that 3 (33.3%) patients had no gene mutations in the tumor tissue, 5 (55.6%) patients had unique TP53 gene mutations, and 1 (11.1%) patient had TP53 and CHEK1 mutations. However, no drugs were available for targeted therapy of the mutated genes. The genetic tumor gene testing results showed that no genetic tumor gene was found in all the patients, suggesting that OSCC had a low possibi-lity of hereditary tumor. In terms of immune efficacy related markers, CPS test results showed that 8 patients had CPS≥1. TMB detection results showed that the median value of TMB value was 0.72 mutations/Mb, and the range was 0 to 4.32 mutations/Mb. The negative and positive control results of microsatellite sequence status were consistent, indicating that all the tumor tissues detected were microsatellite stability. The results of HLA-B detection showed that only one patient had B62 gene mutation, suggesting that the B44 and B62 related genotypes of HLA-B in OSCC tissue samples were low. CONCLUSION: The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.

[EHHADH is a key gene in fatty acid metabolism pathways in hepatocellular carcinoma: a transcriptomic analysis].

OBJECTIVE: To explore the driving gene of hepatocellular carcinoma (HCC) occurrence and progression and its potential as new therapeutic target of HCC. METHODS: The transcriptome and genomic data of 858 HCC tissues and 493 adjacent tissues were obtained from TCGA, GEO, and ICGC databases. Gene Set Enrichment Analysis (GSEA) identified EHHADH (encoding enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase) as the hub gene in the significantly enriched differential pathways in HCC. The downregulation of EHHADH expression at the transcriptome level was found to correlate with TP53 mutation based on analysis of the TCGA- HCC dataset, and the mechanism by which TP53 mutation caused EHHADH downregulation was explored through correlation analysis. Analysis of the data from the Metascape database suggested that EHHADH was strongly correlated with the ferroptosis signaling pathway in HCC progression, and to verify this result, immunohistochemical staining was used to examine EHHADH expression in 30 HCC tissues and paired adjacent tissues. RESULTS: All the 3 HCC datasets showed signficnatly lowered EHHADH expression in HCC tissues as compared with the adjacent tissues (P < 0.05) with a close correlation with the degree of hepatocyte de-differentiation (P < 0.01). The somatic landscape of HCC cohort in TCGA dataset showed that HCC patients had the highest genomic TP53 mutation rate. The transcriptomic level of PPARGC1A, the upstream gene of EHHADH, was significantly downregulated in HCC patients with TP53 mutation as compared with those without the mutation (P < 0.05), and was significantly correlated with EHHADH expression level. GO and KEGG enrichment analyses showed that EHHADH expression was significantly correlated with abnormal fatty acid metabolism in HCC. The immunohistochemical results showd that the expression level of EHHADH in HCC tissues was down-regulated, and its expression level was related to the degree of hepatocytes de-differentiation and the process of ferroptosis. CONCLUSION: TP53 mutations may induce abnormal expression of PPARGC1A to cause downregulation of EHHADH expression in HCC. The low expression of EHHADH is closely associated with aggravation of de-differentiation and ferroptosis escape in HCC tissues, suggesting the potential of EHHADH as a therapeutic target for HCC.

[Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection].

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

[Analysis of incidence and associated factors of preterm birth based on pre-pregnancy body mass index stratification].

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.