Pericoronary adipose tissue attenuation predicts outcome of percutaneous intervention for chronic total occlusion.

AIM: To investigate the association between pericoronary adipose tissue (PCAT) attenuation (PCATA) and outcomes of chronic total occlusion (CTO) after percutaneous coronary intervention (PCI), and to establish a clinical model that can be easily generalised to predict the outcomes of PCI-CTO. MATERIALS AND METHODS: Between September 2015 and September 2019, patients from two centres were enrolled retrospectively. The primary endpoint was a procedural success (defined as achieving residual stenosis of <30% and a grade 3 thrombolysis in myocardial infarction [TIMI] flow). The new predictive model was generated by factors that were determined by multivariate analysis. The PCATA of CTO (PCATA-CTO) score was developed by assigning 1 point for each independent predictor, and then summing all points accrued. In addition, the predictive efficacy and interobserver and intraobserver agreement of PCATA-CTO and other scoring systems based on coronary computed tomography angiography (CCTA) were compared. RESULTS: A total of 201 patients (mean age 58.9 ± 10.8 years, 85% male) were enrolled. The PCI success was achieved in 76% of the lesions. PCAT was higher in the PCI success group (-72.44 ± 10.45HU versus -76.76 ± 10.54 HU, p<0.05). Multivariable analysis yielded severe calcification, lesion length ≥15 mm, and perivascular fat attenuation index (FAI) ≤-69.5HU as independent negative predictors for procedural success. The area under the receiver operating characteristic curves for the PCATA-CTO score was 0.72. Comparing the PCATA-CTO score with other predictive scores, the PCATA-CTO score showed the highest interobserver (kappa = 0.74) and intraobserver agreement (kappa = 0.90, all p<0.01). CONCLUSION: FAI ≤-69.5HU is an independent negative predictor of procedural success. The PCATA-CTO score improved the reliability of the prediction model. Its potential for clinical implementation requires evaluation.

Relationship between coronary microvascular dysfunction (CMD) and left ventricular diastolic function in patients with symptoms of myocardial ischemia with non-obstructive coronary artery disease (INOCA) by cardiovascular magnetic resonance feature-tracking.

AIM: To investigate whether there was an association between coronary microvascular dysfunction (CMD) and left ventricular (LV) diastolic function in patients with myocardial ischemia with non-obstructive coronary artery disease (INOCA). MATERIALS AND METHODS: Our study included 115 subjects with suspected myocardial ischemia that underwent stress perfusion cardiac magnetic resonance (CMR). They were divided into non-CMD and CMD two groups. CMR-derived volume-time curves and CMR-FT parameters were used to assess LV diastolic function using CVI42 software. The latter included global/regional LV peak longitudinal, circumferential, radial diastolic strain rate (LDSR, CDSR, RDSR). Logistic regression analysis was performed with CMR-FT strain parameters as independent variables and CMD as dependent variables, and the effect value was expressed as an odds ratio (OR). RESULTS: Of the 115 patients, we excluded data from 23 patients and 92 patients (56.5% male；52 ± 12 years) were finally included in the study. Of these, 19 patients were included in the non-CMD group (49 ± 11 years) and CMD group included 73patient (52 ± 12 years). The regional CDSR (P=0.019), and regional RDSR (P=0.006) were significantly lower in the CMD group than in non-CMD group. But, regional LDSR in CMD group was higher than non-CMD (P=0.003). In logistic regression analysis, regional LDSR (adjusted ß= 0.1, 95%CI 0.077, 0.349, p=0.002) and RDSR (adjusted ß= 0.1, 95 % CI 0.066, 0.356, p=0.004) were related to CMD. CONCLUSIONS: LV myocardial perfusion parameter MPRI was negatively correlated with LV diastolic function (CDSR) which needs to take into account the degree of diastolic dysfunction.

Coronary microvascular dysfunction: prevalence and aetiology in patients with suspected myocardial ischaemia.

AIM: To evaluate the prevalence, aetiology, and corresponding morbidity of coronary microvascular dysfunction (CMD) in patients with suspected myocardial ischaemia. MATERIALS AND METHODS: The present study included 115 patients with suspected myocardial ischaemia who underwent stress perfusion cardiac magnetic resonance imaging. CMD was assessed visually based on the myocardial perfusion results. The CMR-derived myocardial perfusion reserve index (MPRI) and left ventricular (LV) strain parameters obtained using the post-processing software CVI42 were employed to evaluate LV myocardial perfusion and deformation. LV strain parameters included global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS), global systolic/diastolic longitudinal, circumferential, and radial strain rates (SLSR, SCSR, SRSR, DLSR, DCSR, and DRSR). RESULTS: Of the 115 patients, 12 patients were excluded and 103 patients were finally included in the study. CMD was observed in 79 % (81 patients, aged 53 ± 12 years) of patients. Regarding aetiology, 91 (88 %) patients had non-obstructive coronary artery disease (CAD), eight (8 %) had obstructive CAD, and four (4 %) had hypertrophic cardiomyopathy (HCM). The incidence of CMD was highest (100 %) in patients with HCM, followed by those with non-obstructive CAD (up to 79 %). There were no statistical differences between CMD and non-CMD groups in GCS, GRS, GLS, SRSR, SCSR, SLSR, DCSR, DRSR and DLSR. CONCLUSION: The incidence of CMD was higher in patients with signs and symptoms of ischaemia. CMD occurred with non-obstructive CAD, obstructive CAD, and HCM, with the highest prevalence of CMD in HCM.

Antiviral effect of palmatine against infectious bronchitis virus through regulation of NF-κB/IRF7/JAK-STAT signalling pathway and apoptosis.

1. Infectious bronchitis virus (IBV), a gamma-coronavirus, can infect chickens of all ages and leads to an acute contact respiratory infection. This study evaluated the anti-viral activity of palmatine, a natural non-flavonoid alkaloid, against IBV in chicken embryo kidney (CEK) cells.2. The half toxic concentration (CC50) of palmatine was 672.92 µM, the half inhibitory concentration (IC50) of palmatine against IBV was 7.76 µM and the selection index (SI) was 86.74.3. Mode of action assay showed that palmatine was able to directly inactivate IBV and inhibited the adsorption, penetration and intracellular replication of IBV.4. Palmatine significantly upregulated TRAF6, TAB1 and IKK-ß compared with the IBV-infected group, leading to the increased expressions of pro-inflammatory cytokines IL-1ß and TNF-α in the downstream NF-κB signalling pathway.5. Palmatine significantly up-regulated the levels of MDA5, MAVS, IRF7, IFN-α and IFN-ß in the IRF7 pathway, inducing type I interferon production. It up-regulated the expression of 2'5'-oligoadenylate synthase (OAS) in the JAK-STAT pathway.6. IBV infection induced cell apoptosis and palmatine-treatment delayed the process of apoptosis by regulation of the expression of apoptosis-related genes (BAX, BCL-2, CASPASE-3 and CASPASE-8).7. Palmatine could exert anti-IBV activity through regulation of NF-κB/IRF7/JAK-STAT signalling pathways and apoptosis, providing a theoretical basis for the utilisation of palmatine to treat IBV infection.

Characterization of circRNA expression profiles associated with non-Mendelian inheritance in feather growth of chickens.

1. Non-coding RNAs, such as miRNAs, play a crucial role in chicken feather growth rate. However, circular RNA (circRNA) expression profiles in fast- and slow-feathering chickens that follow and do not follow Mendelian inheritance are unclear.2. The circRNA expression profiles was analysed by RNA sequencing of hair follicles of slow-feathering chickens that follow genetic rules and fast-feathering chickens that did not follow genetic rules. Differentially expressed circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was then constructed and the key factors and regulation mechanisms controlling feather growth rate were identified.3. The results revealed that 67 circRNAs were significantly differentially expressed in hens, including 22 up-regulated and 45 down-regulated circRNAs in non-Mendelian inheritance-mediated fast-feathering hens compared with Mendelian inheritance-mediated slow-feathering hens. In addition, 16 significantly differentially expressed circRNAs were identified in cockerels, including nine up-regulated and seven down-regulated circRNAs in non-Mendelian inheritance-mediated fast- compared with Mendelian inheritance-mediated slow-feathering cocks. Moreover, circRNA-mediated ceRNA regulation of hair follicle formation was particularly abundant in the Jak-STAT, Wnt and Toll-like receptor signalling pathways. Furthermore, circABI3BP was seen to be a crucial circRNA in regulating feather growth rate, by binding with gga-miR-1649-5p to regulate SSTR2 expression.4. In conclusion, this study analysed circRNA expression profiles in fast- and slow-feathering chickens that follow and do not follow Mendelian inheritance, which laid the foundation for understanding the role of circRNA in chicken feather growth rate.

[Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma].

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

[Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study].

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

[Association between long-term exposure to ambient ozone and sperm quality in Shandong Province].

Objective: To evaluate the association between long-term exposure to ambient ozone (O3) and sperm quality. Methods: From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals (CIs) for all sperm parameters associated with 10 µg/m3 increases in O3. The effects of individual characteristics on the association between O3 and sperm quality were evaluated by stratified analysis. Results: The average O3 concentration in the year before semen collection was (107.09±7.50) µg/m3. Each 10 µg/m3 increase in O3 was associated with declined sperm concentration (-3.12%, 95%CI:-4.55%, -1.67%), total sperm count (-5.21%, 95%CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95%CI:-2.37%, -0.61%), progressive motility (-2.53%, 95%CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95%CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95%CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O3 on sperm quality, but the difference was not statistically significant (P>0.05). Conclusion: Long-term exposure to O3 in Shandong Province is associated with a decrease in sperm quality.

[Analysis of clinical characteristics and risk factors of chest tightness variant asthma in children].

Objective: To analyze the clinical features and risk factors of chest tightness variant asthma (CTVA) in children, so as to provide basis for the prevention and management of the disease. Methods: A cross-sectional study was conducted to analyze 178 children aged 6-17 years old who were admitted to the Department of Allergy, Capital Institute of Pediatrics Affiliated Children's Hospital from January 2021 to January 2023 due to chest tightness. The age was 8.83(7.50, 11.58) years old, with 89 males (50%) and 89 females (50%). According to the diagnosis of CTVA, 130 cases were divided into CTVA group and 48 non-CTVA cases were divided into control group. Demographic data, personal history, family history, clinical features, auxiliary examination results and other data were collected. The clinical characteristics, allergens, FeNO level and pulmonary function parameters of the two groups were analyzed. Logistic regression analysis was used to explore the risk factors of the disease. Results: The proportion of school-age children (6-11 years old) in CTVA group was higher than that of adolescent children (≥12 years old) [(113/130,86.9%) vs (26/48,54.2%),Z=21.985,P<0.01]. The proportion of CTVA combined with eczema [(74/130,56.9%) vs (19/48,39.6%), χ2=4.225,P<0.05] and rhinitis symptoms [(98/130,75.4%) vs (27/48,56.2%), χ2=6.138,P<0.05] was higher. The positive rates of mold sensitization [(52/130,40.0%) vs (11/48,22.9%), χ2=4.474,P<0.05] and multiple sensitization [(71/130,54.6%) vs (18/48,37.5%), χ2=4.108,P<0.05] in inhaled allergens were significantly higher than those of control group. The proportion of elevated FeNO (>20 ppb) in CTVA children was 20.8% (27/130), which was significantly higher than that in control group 4.2%(2/48)(χ2=7.086,P<0.01). There were no statistical differences in spirometry parameters FEV1 and FVC between CTVA group and control group (P both>0.05). FEV1/FVC, PEF, FEF25, FEF50, FEF75 and MMEF were significantly lower than those in control group (P all<0.05). Logistic regression analysis showed that rhinitis symptoms (OR=2.351, 95%CI 1.105-5.002, P=0.026), multiple sensitizations (OR=2.184, 95%CI 1.046-4.557, P=0.038), tIgE>60 kU/L(OR=3.080, 95%CI 1.239-7.654, P=0.015), FeNO>20 ppb (OR=6.734, 95%CI 1.473-30.796, P=0.014) and small airway dysfunction (OR=3.164, 95%CI 1.089-9.194, P=0.034) were risk factors for chest tightness variant asthma. FeNO combined with FEF50 has the largest area under the curve (Z=2.744, P<0.01) in diagnosing CTVA. Conclusion: CTVA is more common in school-age children than in adolescent children. Rhinitis symptoms, multiple sensitization, tIgE>60 kU/L, FeNO>20 ppb and small airway dysfunction are risk factors for chest tightness variant asthma. FeNO combined with small airway indexes can improve the diagnostic value of CTVA.

Asperosaponin VI Protects Against Bone Loss Due to Hindlimb Unloading in Skeletally Growing Mice Through Regulating Microbial Dysbiosis Altering the 5-HT Pathway.

Osteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI (AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6 J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200 mg/kg/day). AVI was administrated orally for 4 weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as Clostridium and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss.

Adenosine triphosphate (ATP): a safe and effective vasodilator for stress perfusion cardiac magnetic resonance imaging.

AIM: To evaluate the efficiency and safety of adenosine triphosphate (ATP) as a stress agent in a cohort of patients undergoing stress perfusion cardiac magnetic resonance imaging (CMRI). MATERIALS AND METHODS: This retrospective study was conducted between December 2019 and October 2021. The study recruited patients who underwent stress perfusion CMRI using ATP as a vasodilator. Adverse events, such as chest pain, flushing, dyspnoea, headache, and splenic switch-off (SSO) phenomenon, were evaluated in the patients who underwent stress perfusion CMRI. RESULTS: The study included 107 patients (age range: 53 ± 11 years; male:female, 62%:38%). The haemodynamic response (heart rate increased by ≥ 10 beats/min) was quick and observed within 2 minutes of ATP infusion. Scanning was stopped in three patients because of atrioventricular block. CMRI images of seven out of 104 patients were excluded from the final analysis because of inferior quality. During ATP infusion, 37/107 patients (35%) experienced mild adverse events, such as chest pain, flushing, dyspnoea, headache, and atrioventricular block. Myocardial infarction and bronchospasms were not observed during ATP infusion. SSO, a marker of adequate stress, was observed in 91% (94/103) of the patients who underwent stress perfusion CMRI. CONCLUSIONS: As a coronary vasodilator, ATP was safe for stress perfusion CMRI. In addition, the adverse events during ATP infusion were mild, which were relieved within 2 minutes of ATP injection cessation. SSO could serve as an indicator of stress success in ATP stress perfusion CMRI.

The radiomic biomarker in non-small cell lung cancer: 18F-FDG PET/CT characterisation of programmed death-ligand 1 status.

AIM: To present an integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) radiomic characterisation of programmed death-ligand 1 (PD-L1) status in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: In this retrospective study, 18F-FDG PET/CT images and clinical data of 394 eligible patients were divided into training (n=275) and test sets (n=119). Next, the corresponding nodule of interest was segmented manually on the axial CT images by radiologists. After which, the spatial position matching method was used to match the image positions of CT and PET, and radiomic features of the CT and PET images were extracted. Radiomic models were built using five different machine-learning classifiers and the performance of the radiomic models were further evaluated. Finally, a radiomic signature was established to predict the PD-L1 status in patients with NSCLC using the features in the best performing radiomic model. RESULTS: The radiomic model based on the PET intranodular region determined using the logistic regression classifier preformed best, yielding an area under the receiver operating characteristics curve (AUC) of 0.813 (95% CI: 0.812, 0.821) on the test set. The clinical features did not improve the test set AUC (0.806, 95% CI: 0.801, 0.810). The final radiomic signature for PD-L1 status was consisted of three PET radiomic features. CONCLUSION: This study showed that an 18F-FDG PET/CT-based radiomic signature could be used as a non-invasive biomarker to discriminate PD-L1-positive from PD-L1-negative in patients with NSCLC.

Facial expression of patients with Graves' orbitopathy.

PURPOSE: Patients with Graves' orbitopathy (GO) have characteristic facial expressions that are different from those of healthy individuals due to the combination of somatic and psychiatric symptoms. However, the facial expressions of GO patients have not yet been described and analyzed systematically. Thus, the present study aimed to present the facial expressions of GO patients and explore their applications in clinical practice. METHODS: Facial image and clinical data of 943 GO patients were included, and 126 patients answered quality of life (GO-QOL) questionnaires. Each patient was labeled for one facial expression. Then, a portrait was drawn for every facial expression. Logistic and linear regression was performed to analyze the correlation between facial expression and clinical indicators, including QOL, disease activity and severity. The VGG-19 network model was utilized to discriminate facial expressions automatically. RESULTS: Two groups, i.e., the non-negative emotion (neutral, happy) and the negative emotion (disgust, angry, fear, sadness, surprise), and seven expressions of GO patients were systematically analyzed. Facial expression was statistically associated with GO activity (P = 0.002), severity (P < 0.001), QOL visual functioning subscale scores (P = 0.001), and QOL appearance subscale score (P = 0.012). The deep learning model achieved satisfactory results (accuracy 0.851, sensitivity 0.899, precision 0.899, specificity 0.720, F1 score 0.899, and AUC 0.847). CONCLUSIONS: As a novel clinical sign, facial expression holds the potential to be incorporated into GO assessment system in the future. The discrimination model may assist clinicians in real-life patient care.

Salvage endoscopic surgery for skull base osteoradionecrosis in nasopharyngeal carcinoma patients: A prospective, observational, single-arm clinical study.

BACKGROUND: Postradiation skull base osteoradionecrosis (ORN) is a severe complication that occurs after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that can severely affect quality of life (QOL) and be life threatening. Only 13.4% - 28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced salvage endoscopic surgery for skull base ORN patients and evaluated its clinical efficacy. METHODS: This was a prospective, observational, single-arm clinical study. Clinical data from 18 skull base ORN patients who underwent radical endoscopic necrectomy followed by reconstruction using a septal pedicled mucosal flap or temporal muscle flap were included in the study. The endpoint was an overall survival (OS) of 2 years. The numeric rating scale (NRS) scores for pain and foul odor were analyzed to determine the efficacy and safety of this surgery. RESULTS: A total of 21 patients were recruited, 18 of whom completed the study and were analyzed. All surgeries were successfully performed. During the 2-year study, the OS rate of the entire cohort was 75%. The median NRS score for pain decreased from 6.44 +- 2.62 to 0.50 +- 0.71, and the NRS score for foul odor decreased from 1.89±1.08 to 1 after surgery. CONCLUSIONS: Salvage endoscopic necrectomy followed by construction using a septal pedicled mucosal flap or temporal muscle flap is a novel, safe, and effective treatment for ORN in patients with NPC. CLINICAL TRIAL REGISTRATION: This study was approved by the independent ethics committee of the Eye, Ear, Nose and Throat Hospital of Fudan University (IEC No. 2019095-1). Written informed consent was obtained from all patients. The study was registered with the Chinese Clinical Trial registry (ChiCTR2000029327).

[Based on CT radiomics model for predicting the response to first-line chemotherapy of diffuse large B-cell lymphoma].

Objective: To investigate the potential value of CT Radiomics model in predicting the response to first-line chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods: Pre-treatment CT images and clinical data of DLBCL patients treated at Shanxi Cancer Hospital from January 2013 to May 2018 were retrospectively analyzed and divided into refractory patients (73 cases) and non-refractory patients (57 cases) according to the Lugano 2014 efficacy evaluation criteria. The least absolute shrinkage and selection operator (LASSO) regression algorithm, univariate and multivariate logistic regression analyses were used to screen out clinical factors and CT radiomics features associated with efficacy response, followed by radiomics model and nomogram model. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the models in terms of the diagnostic efficacy, calibration and clinical value in predicting chemotherapy response. Results: Based on pre-chemotherapy CT images, 850 CT texture features were extracted from each patient, and 6 features highly correlated with the first-line chemotherapy effect of DLBCL were selected, including 1 first order feature, 1 gray level co-occurence matrix, 3 grey level dependence matrix, 1 neighboring grey tone difference matrix. Then, the corresponding radiomics model was established, whose ROC curves showed AUC values of 0.82 (95% CI: 0.76-0.89) and 0.73 (95% CI: 0.60-0.86) in the training and validation groups, respectively. The nomogram model, built by combining validated clinical factors (Ann Arbor stage, serum LDH level) and CT radiomics features, showed an AUC of 0.95 (95% CI: 0.90-0.99) and 0.91 (95% CI: 0.82-1.00) in the training group and the validation group, respectively, with significantly better diagnostic efficacy than that of the radiomics model. In addition, the calibration curve and clinical decision curve showed that the nomogram model had good consistency and high clinical value in the assessment of DLBCL efficacy. Conclusion: The nomogram model based on clinical factors and radiomics features shows potential clinical value in predicting the response to first-line chemotherapy of DLBCL patients.

[Preliminary studies on the role of mast cells in the phenotype and immune activation of type 2 inflammatory cytokine release of atopic dermatitis].

Objective: To investigate the role of mast cells in atopic dermatitis (AD) phenotype and the immune activation of type 2 inflammatory cytokine release. Methods: Nine AD skin samples were obtained from the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, and nine healthy skin control samples were obtained from the surgical excision of excess normal skin by orthopedic surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, which were subjected to toluidine blue staining and fluorescence staining to clarify the mast cell degranulation activation status of the AD skin lesions. We investigated whether MC903 could directly activate mast cells in vivo through the toe swelling and exudation assay in wild-type mice; we constructed the MC903-AD model using wild-type and KitW-sh/W-sh mast cell-deficient mice in order to investigate whether mast cells affected the phenotype, histopathology, and the level of type 2 inflammatory factors in AD mice; we extracted mouse peritoneal mast cells and the ability of MC903 to activate mast cells to release inflammatory mediators in vitro was explored by calcium imaging, tryptase and ß-aminohexokinase release assays, and MCP-1 and CXCL-2 release assays. Results: The number of degranulated mast cells in an activated state was increased in skin lesions of AD patients compared to healthy controls, with (5.40±1.14) and (2.20±0.84), respectively (P<0.001). KitW-sh/W-sh mast cell-deficient AD mice had an attenuated phenotype with ADI scores of (5.50±1.05), compared to wild-type AD mice with (10.00±0.89) (P<0.001). The release of type 2 inflammatory factors in wild-type AD mice was higher than those in KitW-sh/W-sh mast cell-deficient AD mice, with IL-4 levels of (29.50±1.87) and (15.33±1.86) pg/mg (P<0.001), IL-13 levels were (6.32±0.25) and (3.93±0.22) pg/mg (P<0.001), IL-31 levels were (9.73±0.38) and (6.89±0.27) pg/mg (P<0.001), and TSLP levels were (206.00±4.43) and (99.00±4.86) pg/mg (P<0.001), respectively. MC903 could cause mast cell activation in wild-type mice, leading to increased swelling and exudation in the toes of mice, and MC903 could activate mast cells in vitro, leading to increased degranulation and release of inflammatory factors such as MCP-1 and CXCL-2. Conclusions: The number of activated mast cells was increased in skin lesions of AD patients than in healthy controls. KitW-sh/W-sh mast cell-deficient AD mice showed significantly reduced phenotype, histopathology, and type 2 inflammatory factor levels compared with wild-type AD mice. MC903 activates mast cells in vivo and in vitro. Mast cells play a key role in AD phenotype and immune activation.

[The influence of interaction between polygenic risk score and intestinal fungal microbiota on the risk of schizophrenia].

Objective: To investigate the effect of interaction between polygenic risk score (PRS) and intestinal fungal microbiota on the risk of Schizophrenia (SCH). Methods: A case-control study was carried out. Drug-naïve, first-episode SCH patients were selected from the Psychiatric Department of the First Affiliated Hospital of Zhengzhou University between October 2017 and October 2019. Meanwhile, healthy controls (HCs) were recruited from local communities through online advertisement or physical examination center. Intestinal fungal microbiota was characterized by the 18S rRNA sequencing platform. The association of fungal microbial dysbiosis (F_MD) index, α-diversity indices and PRS with SCH was detected by logistic regression analysis. Results: A total of 137 SCH patients (62 males and 75 females) and 76 HCs (31 males and 45 females) were included in the study. The age of SCH patients and HCs was (22.5±7.5) years and (22.8±2.3) years, respectively. The results of logistic regression analysis revealed that PRS (OR=1.111, 95%CI: 1.036-1.178, P=0.002) and the increase of F_MD index (OR=1.200, 95%CI: 1.124-1.281, P<0.001) were risk factors for developing SCH. The increase of fungal α-diversity Shannon (OR=0.813, 95%CI: 0.755-0.874, P<0.001) index, Simpson index (OR=0.218, 95%CI: 0.091-0.523, P<0.001) and abundance of key Aspergillus (OR=0.928, 95%CI: 0.864-0.996, P=0.040) decreased the risk of SCH. Aspergillus abundance was positively correlated with cognitive domains including working memory (r=0.280, P=0.001), verbal learning (r=0.253, P=0.003), reasoning and problem solving (r=0.191, P=0.028). Conclusion: The increase of PRS may increase the risk of SCH. The increase of fungal α-diversity indices and Aspergillus abundance may decrease the risk of SCH. The interaction between PRS and intestinal fungi (Shannon index, Simpson index and Aspergillus) is a related factor for the risk of SCH.

[Abnormal changes of static and dynamic functional connectivity of dopaminergic midbrain in patients with first-episode schizophrenia and their correlations with clinical symptoms].

Objective: To investigate the abnormal changes of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in the dopaminergic midbrain (ventral dorsal tegmental area and bilateral substantia nigra compacta, VTA/SNc) in patients with first-episode schizophrenia(SCH), and their correlation with the Positive and Negative Symptom Scale (PANSS). Methods: The data of 198 first-episode untreated schizophrenia patients and 199 healthy controls (HC) matched by age, sex and years of education who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2019 to May 2022 were prospectively collected. All subjects underwent high resolution structural MRI and resting state functional magnetic resonance imaging (rs-fMRI) scanning. The dopaminergic midbrain (VTA/SNc) was defined as three regions of interest (ROI). The sFC and dFC analyses with VTA/SNc as seeds were performed to produce a whole-brain diagram initially, which subsequently were compared between schizophrenia group and HC group. Finally, the correlation analysis of sFC and dFC values with the PANSS scores were performed, including the positive scale score, negative scale score, general psychopathology scale score, total score and symptom scores. Results: There were 86 males and 112 females in SCH group, and aged (23±9) years. Meanwhile, there were 95 males and 104 females in HC group, and aged (22±5) years. In the SCH group, the positive (P), the negative (N) and the general psychopathology (G) scale scores and the total score (T) of the PANSS scale was 20±7, 21±7, 41±11 and 82±22, respectively. Compared with the HC group, the VTA showed decreased sFC with four clusters including cerebellar vermis 7/9, left putamen, right thalamus and left middle cingulate gyrus in the schizophrenia group (peak center, t=-4.35, -4.81, -4.35 and -4.65; voxel P<0.005; cluster P<0.05), the right SNc showed decreased sFC with four clusters including left cerebellar hemisphere 4/5/8, right putamen, right medial orbitofrontal gyrus and the left putamen in the schizophrenia group (peak center, t=-4.91, -5.15, -4.77 and -5.21; voxel P<0.005; cluster P<0.05), and the left SNc showed decreased sFC with four clusters including the left putamen, right putamen, right medial orbitofrontal gyrus and left middle cingulate gyrus in the schizophrenia group (peak center, t=-5.82, -4.83 and -4.65; voxel P<0.005; cluster P<0.05). Compared with the HC group, the VTA showed decreased dFC with the right inferior parietal gyrus, right angular gyrus and right superior parietal gyrus in schizophrenia group (t=-4.17). In the schizophrenia group, the sFC value of cluster 2 (left putamen) with VTA as seed and cluster 4 (left putamen) with right SNc as seed were positively correlated with the positive scale scores in PANSS (r=0.141, 0.169, both P<0.05). The sFC and dFC values of significant regions were also correlated with hallucination, delusion, suspicion, hostility, communication disorder, passivity/indifference, lack of communication, stereotyped thinking, depression, non-cooperation, lack of judgment and insight, impulse control disorder, active social avoidance (all P<0.05). Conclusion: The static and dynamic functional connectivity (stability) of VTA/SNc to cerebellum, thalamus, striatum, prefrontal lobe and cingulate gyrus in first-episode schizophrenia patients were decreased, which were closely related to the positive and negative symptoms of schizophrenia.

[Establishment of diagnostic model for schizophrenia based on neurotrophic factor and other biomarkers].

Objective: To construct a diagnostic model of schizophrenia (SCZ) based on biomarkers such as serum neurotrophic factor. Methods: Patients of schizophrenia (SCZ group) and healthy controls (HC group) who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019 were prospectively selected. In the SCZ group, the mental symptoms were assessed by the positive and negative symptom scale (PANSS), cognitive function was assessed by the MATRICS consensus cognitive battery (MCCB), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), fasting glucose (FGB) and fasting insulin (FINS) levels were detected, and insulin resistance (HOMA-IR) was calculated. The same methods were used to evaluate cognitive function, measure BDNF, GDNF, FGB and FINS levels, and calculate HOMA-IR in HC group. The indexes with statistically significant differences between the two groups were selected to be included in the model. The diagnostic model was constructed by machine learning and verified by cross-validation method, the receiver operating curve (ROC) was plotted, and the area under the curve (AUC), sensitivity and specificity were calculated. Results: (1) A total of 142 patients (70 males and 72 females) with schizophrenia were finally included, and aged (25±4) years. Meanwhile, 140 healthy controls (72 males and 68 females) were also enrolled, and aged (26±4) years. In SCZ group, scores in all areas of cognitive function were lower than those in HC group (all P<0.001), the levels of serum BDNF and GDNF [(6.7±1.8) ng/ml and (405±93) pg/ml] were also lower than those in HC group [(12.3±3.2) ng/ml and (574±139) pg/ml] (both P<0.001), but the levels of FINS and HOMA-IR [(8.4±0.8) µU/ml and 1.7±0.3] were higher than those in HC group [(6.7±0.9) µU/ml and 1.4±0.3] (both P<0.001). (2) Correlation analysis showed that the level of serum BDNF had a negative correlation with negative symptom scores and total scores (r=-0.31, P<0.001; r=-0.17, P=0.040), but had a positive correlation with attention/alertness (CPT-IP) T scores, working memory (WSM-Ⅲ) T scores and visual learning (BVMT) T scores in SCZ group (r=0.39, 0.37 and 0.29, all P<0.001). The level of serum GDNF also had a positive correlation with CPT-IP T scores, WSM-Ⅲ T scores and BVMT T scores (r=0.32, P<0.001; r=0.23, P=0.007; r=0.40, P<0.001). The values of HOMA-IR had a positive correlation with social cognition (MSCEIT) T scores in SCZ group (r=0.18, P=0.033). (3) AUC of the early diagnosis model constructed by combining BDNF, GDNF and HOMA-IR was 0.890 (95%CI: 0.832-0.940), the accuracy was 0.89, the sensitivity and specificity was 0.94 and 0.82, respectively. Conclusion: The final diagnostic model based on biomarkers of serum neurotrophic factor has good diagnostic efficiency for SCZ, but large-scale independent sample verification is still needed.

[Analysis of the relationship between embryo quality at different developmental stages and secondary sex ratio of single live births].

Objective: To investigate the effect of embryo quality at different developmental stages on the secondary sex ratio (SSR) of single live birth neonates. Methods: Data for patients with singleton live births after embryo transferred between January 2016 and January 2022 were retrospectively analyzed. The effect of embryo quality at different development stages on the SSR of 11 713 singleton live births were investigated. The association of SSR and embryo quality at different development stages was examined in univariate analysis and in a multivariate logistic regression model, after adjustment for confounders, using two models (Ⅰ and Ⅱ). Results: The age of both male and female, body mass index of both male and female, basal follicle stimulating hormone and estradiol, smoking of male, methods of insemination, methods of sperm extraction, types of transfer cycle and the number of embryo transferred were not related with SSR (all P>0.05). After adjustment for confounders, the probability of a male live birth was higher after transfer of good-quality blastula than after transfer of poorer-quality blastula (model Ⅰ: aOR=0.73, 95%CI: 0.65-0.82, P<0.001; model Ⅱ: aOR=0.73, 95%CI: 0.65-0.82, P<0.001). The quality of cleavage stage embryo was not associated with SSR (model Ⅰ: aOR=0.99, 95%CI: 0.87-1.13, P=0.937; model Ⅱ: aOR=0.99, 95%CI: 0.87-1.13, P=0.899). Conclusions: The SSR of singleton live births after embryo transfer is not correlated with the quality of cleavage stage embryo, but is correlated with the quality of blastula. Good-quality blastula transfer is more likely to result in a male live birth.