[The efficacy and safety of laparoscopic radical gastrectomy after neoadjuvant chemotherapy combined with immunotherapy and targeted therapy].

Objectives: To explore the efficacy and safety of laparoscopic radical gastrectomy after neoadjuvant chemotherapy combined with immunotherapy and targeted therapy in patients with gastric cancer. Methods: A retrospective analysis of clinical and pathological data of 20 patients with locally advanced gastric cancer (clinical TNM stage T3-4aN+M0) admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from July 2021 to July 2023. All patients received 3 cycles of SOX (Oxaliplatin+S-1) regimen combined with immunotherapy (Trastuzumab) and targeted therapy (Apatinib) as neoadjuvant treatment followed by laparoscopic radical gastrectomy for gastric cancer. Surgical outcomes, postoperative pathological response, and postoperative recovery were observed. Quantitative data, except for age and operation time, were expressed using Median (range). Results: Among the 20 patients, there were 18 males and 2 females, aged 41 to 73 years [(60.6±9.7) years]. All 20 patients underwent laparoscopic surgical treatment after neoadjuvant therapy, with one patient undergoing laparoscopic conversion to open total gastrectomy with partial transverse colon resection due to tumor invasion into the transverse mesocolon. Eight patients underwent totally laparoscopic radical gastrectomy, all with Billroth Ⅱ+Braun anastomosis at the distal stomach. Eleven patients underwent laparoscopic-assisted radical gastrectomy, among which total gastrectomy with Roux-en-Y anastomosis was performed in ten cases, and proximal gastrectomy with esophagogastrostomy overlap anastomosis was performed in one case. The mean operation time for the 20 patients was (165.0±34.1) minutes; intraoperative blood loss was 80 (20-100) ml; and the number of lymph nodes retrieved was 68 (21-89). Postoperative pathological TNM staging revealed stage T0N0M0 in six cases, stage Ⅰ in two cases, stage Ⅱ in three cases, and stage Ⅲ in nine cases. Six patients (30.0%) achieved pathological complete response, and nine patients (45.0%) achieved significant pathological response. The median postoperative time to flatus was 4 (1-5) days; oral intake resumed after 3 (2-5) days; and the median length of hospital stay was 13 (6-19) days. One patient developed colonic anastomotic leakage with intra-abdominal infection, and one patient developed duodenal stump leakage with intra-abdominal infection, both classified as Clavien-Dindo grade 3A complications, and improved after treatment and discharged. One patient developed gastric paresis, and two patients developed pleural effusion, classified as Clavien-Dindo grade 2 complications, and improved after treatment and discharged. There were no deaths within 30 days after discharge. Conclusions: Laparoscopic radical gastrectomy for gastric cancer after neoadjuvant treatment with the SOX regimen combined with immunotherapy and targeted therapy is safe and feasible, with satisfactory short-term efficacy. However, there is an increase in overall surgical risk and difficulty, and it is recommended to be performed in experienced gastric cancer centers.

Assessing the feasibility of SUVindex (a metric derived from FDG PET/CT) for the diagnosis of polymyalgia rheumatica.

AIM: To evaluate the feasibility of standard uptake value (SUV) index (ratio lesional maximum SUV [SUVmax] to liver mean SUV [SUVmean]) as a metabolic parameter for diagnosing polymyalgia rheumatica (PMR). MATERIALS AND METHODS: A retrospective group of patients with PMR and controls with symptoms similar to PMR but diagnosed with other diseases. Semiquantitative and qualitative analysis of 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake at 18 sites was undertaken for all patients. The diagnostic value of positron-emission tomography/computed tomography (PET/CT) for PMR was assessed by R software using logistic regression and a generalised additive model (GAM). All images were examined independently by two nuclear medicine physicians with extensive work experience. RESULTS: The characteristic sites of PMR were the ischial tuberosity, interspinous bursa, periarticular hip, and symphysis pubis enthesis. The area under the curve (AUC) of the characteristic site SUV index was 0.930, and the best cut-off value was 1.685 with a sensitivity of 84.6% and a specificity of 92.6%. After adjusting for potential confounders, the probability of PMR diagnosis increased as the characteristic site SUV index increased and there was a nonlinear correlation between the two. When the characteristic site SUV index was ≥2.56, the probability of PMR gradually reached the threshold effect, which was as high as 90% or more. CONCLUSION: The characteristic site SUV index is an independent factor for diagnosing PMR, and PMR should be highly suspected when it is ≥ 1.685. Nonetheless, it is important to note that these findings are based on an initial retrospective single-centre study and require external validation and further prospective evaluation before being translated into clinical practice.

Breast cancer diagnosis and prognosis using a high b-value non-Gaussian continuous-time random-walk model.

AIM: To compare the diagnostic performance of mono-exponential model-derived apparent diffusion coefficient (ADC), continuous-time random-walk (CTRW) model-derived Dm, α, ß and their combinations in discriminating malignancy of breast lesions, and investigate the association between model-derived parameters and prognosis-related immunohistochemical indices. MATERIALS AND METHODS: A total of 85 patients with breast lesions (51 malignant, 34 benign) were analysed in this retrospective study. Clinical characteristics include oestrogen receptor (ER), progesterone receptor (PR), human epidermal receptor 2 (HER2), and Ki-67. The ADC was fitted using a mono-exponential model (b-values = 0, 800 s/mm2), while Dm, α, and ß were fitted using a CTRW model. Independent Student's t-test and the Mann-Whitney U-test were used for the comparison of parameters. Discrimination performance was accomplished by receiver operating characteristic (ROC) analysis, and Spearman's correlation analysis was used to explore the association between immunohistochemical indices and diffusion parameters, the statistical significance level was p<0.05. RESULTS: Dm and ADC demonstrated similar performance in differentiating malignant and benign lesions (AUC = 0.928 versus 0.930), while the combination of Dm, α, and ß could improve the AUC to 0.969. The combined parameter generated by ADC, Dm, α, and ß was effective in identifying the ER+/ER- and PR+/PR- patients. Temporal heterogeneity parameter α correlated significantly with the expression of PR. CONCLUSION: Diffusion parameters derived from the CTRW model could effectively discriminate the malignancy of breast lesions. Meanwhile, the hormone receptor expression could be distinguished by combined diffusion parameters, and have the potential to reflect the prognosis.

"Triple-low" radiation dose bronchial artery CT angiography before bronchial artery embolisation: a feasibility study.

AIM: To explore the feasibility of a "triple-low" dose (low tube voltage, low tube current, and low contrast agent volume) bronchial artery computed tomography (CT) angiography (CTA) to replace routine dose bronchial artery CTA before bronchial artery embolisation (BAE). MATERIALS AND METHODS: CTA was obtained from 60 patients with body mass index (BMI) < 30 kg/m2 using a 256 multi-section iCT system, and they were divided into two groups: (1) group A: 100 kVp, 100 mAs, 50 ml contrast medium (CM); (2) group B: 120 kVp, automatic tube current modulation (ACTM), 80 ml CM. CT attenuation of the thoracic aorta, image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated, and subjective image quality scores and traceability scores assessed. The effective radiation dose was calculated. RESULTS: The radiation dose was reduced by 79.7% in group A compared to group B (p<0.05). The CT attenuation of the thoracic aorta was increased by approximately 13% in group A compared to group B (p<0.05). Higher image noise, lower SNR, and CNR were obtained in group A compared to group B (all p<0.05). Both subjective image quality scores and traceability scores did not differ between groups A and B (both p>0.05). CONCLUSION: It is feasible to use the "triple-low" dose CTA protocol for patients with a body mass index (BMI) < 30 kg/m2. The radiation dose was reduced by 79.7%, and the dose of contrast medium was reduced by 37.5% to ensure the diagnostic value.

Development and validation of risk prediction models for stroke and mortality among patients with type 2 diabetes in northern China.

BACKGROUND: Stroke is one of the leading causes of disability and mortality in patients with type 2 diabetes mellitus (T2DM). Risk models have been developed for predicting stroke and stroke-associated mortality among patients with T2DM. Here, we evaluated risk factors of stroke for individualized prevention measures in patients with T2DM in northern China. METHODS: In the community-based Tianjin Chronic Disease Cohort study, 58,042 patients were enrolled between January 2014 and December 2019. We used multiple imputation (MI) to impute missing variables and univariate and multivariate Cox's proportional hazard regression to screen risk factors of stroke. Furthermore, we established and validated first-ever prediction models for stroke (Model 1 and Model 2) and death from stroke (Model 3) and evaluated their performance. RESULTS: In the derivation and validation groups, the area under the curves (AUCs) of Models 1-3 was better at 5 years than at 8 years. The Harrell's C-index for all models was above 0.7. All models had good calibration, discrimination, and clinical net benefit. Sensitivity analysis using the MI dataset indicated that all models had good and stable prediction performance. CONCLUSION: In this study, we developed and validated first-ever risk prediction models for stroke and death from stroke in patients with T2DM, with good discrimination and calibration observed in all models. Based on lifestyle, demographic characteristics, and laboratory examination, these models could provide multidimensional management and individualized risk assessment. However, the models developed here may only be applicable to Han Chinese.

Retrospective analysis of medical emergencies in an oral emergency department.

BACKGROUND: To retrospectively analyze the rescue of medical emergencies and critical patients in the oral emergency department in a hospital during the past 14 years; analyze the general condition of patients, their diagnosis, etiological factors, and outcomes of the disease, so as to improve the ability of oral medical staff to deal with emergencies; and optimize the emergency procedures and resource allocation in such departments. MATERIAL AND METHODS: Data and related information of critical patient emergency rescue from the Emergency Department of the Hospital of Stomatology, Peking University from January 2006 to December 2019, were analyzed. RESULTS: A total of 53 critical patients were rescued in the oral emergency department in the past 14 years, which is an average of four cases per year, with an incidence rate of 0.00506%. The main type of emergency included hemorrhagic shock and active hemorrhage, with the highest incidence being in the age group of 19-40 years old. Among these cases, 67.92% (36/53) developed emergency and critical diseases before visiting the oral emergency department and 41.51% (22/53) had systemic diseases. After rescue, a total of 48 patients (90.57%) had stable vital signs and 5 (9.43%) died. CONCLUSIONS: Oral doctors and other medical staff should be able to rapidly identify medical emergencies in oral emergency departments and commence emergency treatment. The department should be equipped with relevant first-aid drugs and devices, and medical staff should be regularly trained in practical first-aid skills. Patients with oral and maxillofacial trauma, massive hemorrhage and systemic diseases should be evaluated and treated according to their conditions and systemic organ function to prevent and reduce medical emergencies.

[Tumor necrosis factor-related apoptosis-inducing ligand gene polymorphism and its plasma phenotype in relation to Crohn's disease].

Objectives: To investigate the associations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene polymorphism and plasma soluble TRAIL level (sTRAIL) with Crohn's disease (CD) and to retrospectively analyze the effects of TRAIL gene variants and plasma sTRAIL levels on clinical response to infliximab (IFX). Methods: From January 2012 to January 2021, 312 CD patients [205 males, 107 females, average age (33.9±9.8) years] and 514 age-and gender-matched healthy controls [304 males, 210 females, average age (34.9±9.4) years] were recruited from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. Among them, 72 patients with active CD who were ineffective or intolerant to traditional drug therapy regularly received IFX (5 mg/kg) treatment. According to the changes in the Harvey-Bradshaw index (HBI) and the Simplified Endoscopic Score for Crohn's Disease (SES-CD) in the 14th week, these patients were classified into response group (a decrease in HBI≥3 or a decrease in SES-CD≥50%) and non-response group. TRAIL (rs1131568) gene polymorphism was analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry technique. The plasma sTRAIL level was examined by enzyme-linked immunosorbent assay (ELISA). Based on the Montreal CD classification criteria, all CD patients were divided into different subgroups. Finally, a comprehensive analysis was performed to investigate the relationship between TRAIL (rs1131568) gene polymorphism, the plasma sTRAIL level and the risk of CD, the clinicopathological characteristics of CD patients, and the clinical response to IFX. Results: The recessive model analysis showed that the homozygous variant genotype (CC) was more prevalent in patients with moderately to severely active CD than in those with mildly active CD (45.34% vs 29.23%, P=0.005). Both variant allele (C) and homozygous variant genotype (CC) in patients with stricturing and penetrating CD were more frequent than those in patients with non-stricturing and non-penetrating CD (65.48% vs 57.53%, P=0.046; 49.21% vs 31.18%, P=0.001). The dominant model analysis showed that variant allele (C) and variant genotype (TC+CC) was higher in CD patients with perianal lesions than in those without perianal lesions (66.83% vs 58.17%, P=0.037; 92.31% vs 78.37%, P=0.002). The average plasma sTRAIL level was higher in CD patients than in healthy controls [(243.04±42.74) ng/L vs (194.16±31.14) ng/L, P<0.001]. Compared with the patients with mildly active CD, the plasma sTRAIL level was increased in those with moderately to severely active CD [263.47(242.09, 281.91) ng/L vs 231.13(211.11, 247.11) ng/L, P<0.001]. The same conclusion was also drawn for the patients with stricturing and penetrating CD in contrast to those with non-stricturing and non-penetrating CD [266.18 (246.68, 289.91) ng/L vs 227.19 (204.57, 249.59) ng/L, P<0.001]. The plasma sTRAIL level was also higher in patients with perianal disease than in those without perianal disease [(261.40±41.51) ng/L vs (233.86±40.41) ng/L, P<0.001]. Multiple linear regression analysis further showed that disease activity (ß=22.640, P<0.001) and homozygous variant genotype (CC) (ß=16.814, P<0.001) may be positively related to the plasma sTRAIL level in CD patients independently. At the 14th week of IFX treatment, the plasma sTRAIL level in the response group was lower than that in the non-response group [205.98(190.72, 214.56) ng/L vs (238.33±29.38) ng/L, P<0.001]. Compared with week 0, the plasma sTRAIL level was decreased in the response group in the 14th week [(205.98 (190.72, 214.56) ng/L vs (239.89±42.43) ng/L, P<0.001]. Non-conditional logistic regression analysis showed that variant allele (C) and variant genotype (TC+CC) were less frequent in the response group than in the non-response group (53.33% vs 70.83%, P=0.037; 70.00% vs 91.67%, P=0.036). Conclusions: The increased plasma sTRAIL level may be a risk factor for CD. TRAIL (rs1131568) gene variation and the increase of plasma sTRAIL level may be associated with the increased disease activity of CD and may be the risk factors for stenosis, penetration, and perianal lesions in CD patients. In addition, TRAIL (rs1131568) gene variation or the increase of plasma sTRAIL level may be related to no response to IFX treatment in CD patients.

[Analysis on the efficacy of dual vein induction therapy of Ustekinumab in complex perianal fistulizing Crohn's disease].

Objectives: To analyze the efficacy of dual vein induction therapy of Ustekinumab (UST) in complex perianal fistulizing Crohn's disease (PFCD). Methods: Clinical data of patients diagnosed with complex PFCD in the Second Affiliated Hospital of Wenzhou Medical University from January 2022 to March 2023 were retrospectively analyzed. After sufficient single intravenous infusion of UST (6 mg/kg) at week 0 and 8, every patient received single subcutaneous injection of UST 90 mg every 8 weeks for maintenance treatment. At week 8, 16, and 22-26, clinical outcomes of anal fistula were evaluated using perianal disease activity index (PDAI), and overall activity of the patients was evaluated using Harvey Bradshaw index (HBI). At week 22-26, Van Assche Index (VAI) was used to evaluate imaging outcome of anal fistula, and simplified endoscopic score of Crohn's disease (SES-CD) was employed to assess intestinal outcome events. The above indexes were compared in the patients before and after UST treatment. PFCD patients were divided into first-line UST treatment group and non first-line UST treatment group according to whether first-line UST treatment was used, the differences in anal fistula response rate and remission rate, intestinal response rate and remission rate as well as overall activity response rate and remission rate were compared between the two groups. Results: A total of 60 PFCD patients were included, including 46 males and 14 females, aged [M (Q1, Q3)] 25.0 (20.8, 30.0) years old. The clinical response rates of anal fistula [41.7% (25/60), 55.0% (33/60) and 63.3% (38/60), respectively, P=0.056] and the clinical remission rates of anal fistula [21.7% (13/60), 31.7% (19/60) and 43.3% (26/60), respectively, P=0.002] gradually increased at week 8, 16, 22-26. The overall activity response rates [53.3% (32/60), 70.0% (42/60), 83.3% (50/60), respectively, P=0.040] and the overall activity response rates [41.7% (25/60), 61.7% (37/60), 75.0% (45/60), respectively, P=0.001] also gradually increased at week 8, 16, 22-26. At week 22-26, the partial response rate and fistula healing rate of anal fistula imaging were 45.0% (27/60) and 38.3% (23/60), respectively. The endoscopic response rate and endoscopic response rate were 73.7% (44/60) and 45.0% (27/60), respectively. The endoscopic response rate of patients receiving first-line UST treatment [23 males and 8 females, aged 22.0 (21.0, 39.0) years] was higher than that of patients receiving non first-line UST treatment[23 males and 6 females, aged 26.5 (20.0, 30.0) years,87.1% vs 58.6%, P=0.013]. Conclusion: The dual vein induction therapy of UST could effectively improve the clinical efficacy in patients with complex PFCD.

[Incremental value of epicardial fat volume on predicting obstructive coronary artery disease with myocardial ischemia].

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm3 and (105.18±31.16)cm3, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.

HLA class II immunogenic mutation burden predicts response to immune checkpoint blockade.

BACKGROUND: Whereas human leukocyte antigen (HLA) class I mutation-associated neoantigen burden has been linked with response to immune checkpoint blockade (ICB), the role of HLA class II-restricted neoantigens in clinical responses to ICB is less studied. We used computational approaches to assess HLA class II immunogenic mutation (IMM) burden in patients with melanoma and lung cancer treated with ICB. PATIENTS AND METHODS: We analyzed whole-exome sequence data from four cohorts of ICB-treated patients with melanoma (n = 110) and non-small-cell lung cancer (NSCLC) (n = 123). MHCnuggets, a neural network-based model, was applied to estimate HLA class II IMM burdens and cellular fractions of IMMs were calculated to assess mutation clonality. We evaluated the combined impact of HLA class II germline genetic variation and class II IMM burden on clinical outcomes. Correlations between HLA class II IMM burden and density of tumor-infiltrating lymphocytes were computed from expression data. RESULTS: Responding tumors harbored a significantly higher HLA class II IMM burden for both melanoma and NSCLC (P ≤ 9.6e-3). HLA class II IMM burden was correlated with longer survival, particularly in the NSCLC cohort and in the context of low intratumoral IMM heterogeneity (P < 0.001). HLA class I and II IMM landscapes were largely distinct suggesting a complementary role for class II IMMs in tumor rejection. A higher HLA class II IMM burden was associated with CD4+ T-cell infiltration and programmed death-ligand 1 expression. Transcriptomic analyses revealed an inflamed tumor microenvironment for tumors harboring a high HLA class II IMM burden. CONCLUSIONS: HLA class II IMM burden identified patients with NSCLC and melanoma that attained longer survival after ICB treatment. Our findings suggest that HLA class II IMMs may impact responses to ICB in a manner that is distinct and complementary to HLA class I-mediated responses.

Serum fibrinogen-like protein 1 as a novel biomarker in polycystic ovary syndrome: a case-control study.

PURPOSE: To investigate the relationship between fibrinogen-like protein 1 (FGL-1) concentrations and various metabolic characteristics in patients with polycystic ovary syndrome (PCOS) and explore whether FGL-1 could be a predictive biomarker for PCOS. METHODS: This case-control study included 136 patients with PCOS and 34 normal controls recruited in the Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital between May 2017 and June 2021. Anthropometric characteristics, metabolic parameters, and reproductive hormones were collected. Serum FGL-1 measurement was conducted using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Serum FGL-1 concentrations were higher in patients with PCOS than in control subjects in body mass index (BMI) subgroups, insulin resistance (IR) subgroups, and hepatic function subgroups, respectively. Serum FGL-1 concentrations were significantly associated with BMI, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-c), and serum uric acid (SUA) in all individuals. The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff value for FGL-1 levels to predict PCOS was 21.02 ng/ml with a sensitivity of 74.3% and a specificity of 70.6%. Both univariate and multiple logistic regressions indicated that the odds ratio (OR) for PCOS significantly increased in the subjects with high levels of FGL-1. CONCLUSION: In our study, FGL-1 was associated with serum aminotransferase and various metabolic indexes. Moreover, the high risk of PCOS was independently associated with the increased FGL-1 levels, which suggested that FGL-1 could be a predictive biomarker for PCOS.

[Attach importance to the research of membrane surgery in an era of precision medicine].

The "Metastasis type V", "Envelope" theory and other concepts have been proposed to make gastric surgeons have a full understanding of the importance of mesogastrium, and the correct identification of the boundary of the mesogastrium is the premise of the complete mesogastrium excision(CME), and also the best way to achieve truly standardized D2 lymph node dissection for gastric cancer. In this paper, the boundary of the mesogastrium during complete mesogastrium excision for gastric cancer and how to achieve this operation in practice were studied, which help gastric surgeons finally find the mesogastrium tissue distributed throughout the gastric cancer surgery to achieve the best surgical treatment effect.

[The associations of cyclin-dependent kinase inhibitor 2B antisense RNA 1 gene polymorphisms with the risk of Crohn's disease in Chinese patients].

Objectives: The present study aimed to investigate the associations of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms with the risk of Crohn's disease (CD) in Chinese patients. Methods: From January 2012 to January 2021, a total of 207 CD patients and 545 age-and gender-matched healthy controls were collected from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. The genotypes of CDKN2B-AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) were determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression analysis was used to analyze the differences of CDKN2B-AS1 polymorphisms between CD patients and healthy controls, as well as their influences on the clinicopathologic characteristics of CD patients. The analyses for linkage disequilibrium and haplotype were further performed by Haploview 4.2 software. Results: The variant genotype (AG+GG) and variant allele (G) of rs1063192 were more prevalent in CD patients than in healthy controls (32.4% vs 24.8%, P=0.036; 18.8% vs 13.6%, P=0.011). The same conclusions were also drawn for homozygous variant genotype (GG) and variant allele (G) of rs10757274 when CD patients were compared with healthy controls (19.8% vs 12.8%, P=0.017; 45.2% vs 38.1%, P=0.012). According to the Montreal Classification Standards, CD patients were stratified into different subgroups. The homozygous variant genotype (GG) and variant allele (G) of rs10757278 were less frequent in the patients with stricturing CD or penetrating CD than in those with non-stricturing and non-penetrating CD (13.7% vs 29.9%, P=0.015; 37.7% vs 50.4%, P=0.022). However, all the correlations above were no longer significant after Bonferroni's correction (all P>0.05). The polymorphic loci of rs10757274, rs2383207, rs10757278, and rs1333048 were in close linkage disequilibrium with each other in CDKN2B-AS1 gene. Compared with healthy controls, the frequency of haplotype AGAC was decreased in CD patients (1.5% vs 4.5%, χ2=7.61, P=0.006), whereas the frequency of haplotype GGAC was obviously increased in CD patients (3.0% vs 0.6%, χ2=14.25, P<0.001). The stratified analysis further showed that the frequency of haplotype AGAC was higher in the patients with stricturing CD or penetrating CD than in those with non-stricturing and non-penetrating CD (3.1% vs 0.4%, χ2=5.31, P=0.021). Conclusions: The variations of CDKN2B-AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) may not independently affect the risk of CD. Among the haplotypes constructed by rs10757274, rs2383207, rs10757278, and rs1333048, the haplotype AGAC may reduce the risk of CD, whereas it may increase the risk of stricturing or penetrating in CD patients. In addition, the haplotype GGAC may increase the risk of CD.

Identification and Verification of the Ability of Cdk5 to Phosphorylate Deubiquitinating Enzyme BRCC3 In Vitro.

It is known that the expression of the deubiquitinating enzyme BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and cyclin-dependent protein kinase 5 (Cdk5) is increased in Parkinson's disease (both are involved in neuroinflammatory response). However, the regulatory mechanism of Cdk5 on the post-translational modification of BRCC3 remains unclear. Here we studied whether Cdk5 phosphorylates BRCC3. Phosphorylation of BRCC3 by Cdk5 was predicted by GPS 5.0 software. His-BRCC3 plasmid was constructed by cloning the BRCC3 gene into pGEX-6P-1 vector, and then His-BRCC3 fusion protein was induced with isopropyl ß-d-1-thiogalactopyranoside and purified using His-Tag affinity chromatography purification agarose. Phosphorylation of BRCC3 fusion protein by Cdk5 in vitro was detected by mass spectrometry and Western blotting. The results showed that multiple phosphorylation sites were predicted by GPS 5.0, and the His-BRCC3 fusion protein was successfully induced and purified. In vitro kinase assay, Western blotting, and mass spectrometry showed that Cdk5 can phosphorylate BRCC3. It has been demonstrated that protein kinase Cdk5 can phosphorylate the deubiquitinating enzyme BRCC3 in vitro, which provides new data for further study on the mechanism of neurodegeneration.

[Correlation of clinical joint function with histopathological features of knee joint fibrosis].

Objective: To investigate the correlation between the joint function and the histologic grading after total knee arthroplasty, to aid in the early diagnosis and prognostication of arthrofibrosis. Methods: A total of 29 patients including 22 females and 7 males were enrolled retrospectively from October 2015 to October 2020. These patients had a mean age of 63 years (range 41 to 79 years) and underwent total knee revision in Jishuitan Hospital due to joint contraction or loss of range of motion. Histologic assessment was carried out by utilizing immunohistochemistry (IHC) and the Masson staining to evaluate the fibrosis and inflammation of the samples. Results: By light microscopy, early stage arthrofibrosis showed massive proliferation of myofibroblasts and fibroblasts with SMA expression by IHC. In late stage arthrofibrosis, hyaline degeneration occured with extensive hyperplasia of fibrosis-related tissue. The arthrofibrosis samples appeared blue with Masson staining. Lymphocytes showed perivascular distribution. The arthrofibrosis tissue was mostly grade 3 (26 samples) in histologic assessment, moderate grade (25 samples) in ALVAL score, and grade 1 (23 samples) in lymphocyte grading. Fibrosis grading showed an overwhelming correlation with range of motion (ROM) of the joint. The ALVAL score was highly correlated with the WOMAC score. There was also a direct correlation between inflammatory cell infiltration and pain. The fibrosis grading joint with ALVAL score showed a good predictive value of joint function after joint replacement surgery. Conclusions: The histologic assessment score is closely correlated to the joint function with predictive values for the prognosis after joint replacement surgery.

[Prognostic factor analysis of patients with unresectablelung squamous cell carcinoma].

Objective: To investigate the prognostic factors associated with unresectable (stage Ⅲa-Ⅳ, according to the 7th edition of the AJCC cancer staging manual) lung squamous cell carcinoma. Methods: We retrospectively analyzed 350 patients with inoperable locally advanced, recurrent or metastatic lung squamous cell carcinoma who were admitted to the First Affiliated Hospital of Chinese Medical University from January 2005 to June 2018. The clinical pathological data, treatment and survival follow-up information of the patients were collected. Kaplan-Meier survival was used to compare the overall survival rate of different risk groups. Univariate analysis and multivariate Cox regression analysis were used to determine the independent prognostic factors. Results: A total of 350 patients were enrolled. The median overall survival (OS) of these patients was 16.7 months. Univariate analysis showed the stage, Eastern Cooperative Oncology Group(ECOG), first-line chemotherapy evaluation (RECIST version 1.1), radiation therapy, number of systemic chemotherapy lines, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), C reactive protein (CRP), lactate dehydrogenase (LDH), whether liver, brain, boneor metastasis were associated with the OS of patients with advanced lung squamous cell carcinoma (all P<0.05). Multivariate analysis showed that ECOG score (HR=1.855, 95% CI: 1.063-3.239, P=0.030), whether underwent lung resection (HR=0.476, 95%CI: 0.302-0.751, P=0.001), first-line chemotherapy evaluation [stable disease (SD): HR=0.293, 95%CI: 0.159-0.540, P<0.001; complete response (CR)+ partial response (PR): HR=0.223, 95%CI: 0.120-0.413, P<0.001], CRP (HR=1.715, 95% CI: 1.080-2.723, P=0.042), LDH (HR=1.116, 95%CI: 0.780-1.596, P=0.002) and CEA (HR=1.855, 95%CI: 1.361-2.528, P<0.001) before chemotherapy, liver metastasis (HR=2.453, 95%CI: 1.461-4.120, P=0.001) are independent prognostic factors for patients with unresectable lung squamous cell carcinoma. Conclusion: The ECOG score, surgical treatment history, first-line chemotherapy, LDH, CEA and CRP before chemotherapy, liver metastasis are independent prognostic factors for patients with advanced lung squamous cell carcinoma.

[Emergency training need and effect evaluation analysis of novel coronavirus pneumonia in centers of disease control and prevention].

A questionnaire was used to investigate the emergency training needs of novel coronavirus pneumonia of disease prevention and control institutions in provinces, deputy provincial level regions and cities specifically designated in the state plan, and the effect evaluation of emergency training activities conducted by Chinese Center for Disease Control and Prevention (China CDC). The results showed that 67.4% of 47 disease prevention and control institutions (31/46) believed that the emergency training at the initial stage of the epidemic should be conducted as soon as possible, and the form of network training should be given priority. The training should focus on the urgently needed technologies such as epidemiological investigation, formulation and response of prevention and control strategies, laboratory testing, etc. The teaching materials should highlight pertinence and practicability and be presented in the form of electronic video. The average satisfaction score of the video training conducted by China CDC was (8.81±1.125) and the score of audio-video courseware was (8.97±0.893). The needs analysis and evaluation of novel coronavirus pneumonia prevention and control in disease prevention and control institutions could provide reference for the follow-up training and improve the emergency training management.

[Establishment of a nomogram model for predicting bleeding risk based on endoscopic ultrasound and clinical data among patients with liver cirrhosis].

Objective: To study the predictive value for esophageal variceal bleeding (EVB) after esophageal variceal ligation (EVL) based on clinical data and endoscopic ultrasound examination among patients with liver cirrhosis. Methods: Routine endoscopy and endoscopic ultrasound were performed on 400 preventive EVL cases who met the enrollment criteria, and their clinical indicators, microscopic manifestations, diameter and number of peripheral collateral veins, para-esophageal veins, perforating veins, and so on were monitored. Multivariate Cox proportional hazard regression analysis was performed to determine the relevant factors. Nomogram predictive model was established based on the independent prognostic factors. Nomogram internal validation was carried out with C-index to check the prediction accuracy, calibration curve evaluation consistency, and clinical benefit evaluation for decision-making. Results: Age, gender, etiology, peri-ECV number, para-ECV diameter, portal vein diameter, and azygous vein diameter were the risk factors for disease progression (P < 0.05), and they were all included in the establishment of nomogram. The C-index obtained by internal validation was 0.864, and the area under the receiver operating characteristic curve (AUC) of the predicting bleeding progression model was 0.994 (P < 0.001), suggesting that the disease had high predictive value and the calibration curve validity had consistency. Conclusion: Nomogram predictive model established based on the clinical data and endoscopic ultrasound examination is a preventive and therapeutic intervention for liver cirrhotic patients with esophageal varices, which can effectively improve the therapeutic effects of this population, reduce the EVs occurrence, and improve their quality of life. In addition, it also has an outstanding favorable performance. Therefore, it has certain guiding significance for the judgment of clinical treatment.

[Development of a quality of life questionnaire for adults with anisometropic amblyopia].

Objective: To develop and validate the health-related quality of life (HRQOL) questionnaire for adult patients with anisometropic amblyopia. Methods: Cross-sectional study. A total of 170 adult patients with anisometropic amblyopia, 100 adult patients with other eye diseases and 80 healthy adults with normal vision were recruited at the First Affiliated Hospital of Nanjing Medical University, and 20 healthy adults with normal vision were recruited at Qinhuai Medical District of Easter Theater General Hospital of PLA from December 2019 to February 2020. Individual interviews of 30 adult patients with anisometropic amblyopia generated 80 questionnaire items. For item reduction, 40 adult patients with anisometropic amblyopia were asked to complete the 80-item questionnaire and responses were analyzed. Then factor analyses were performed to identify prominent factors (subscales). The reliability of the questionnaire was evaluated by Cronbach's α coefficient. The overall and sub-scale scores were the average scores of all included items, ranging from 0 (worst HRQOL) to 100 (best HRQOL). The final 20-item questionnaire was administered to additional 100 adult patients with anisometropic amblyopia, 100 adult patients with other eye diseases and 100 visually normal adults. Mean overall and subscale scores were compared across groups using one-way analysis of variance. Results: The final adult anisometropic amblyopia questionnaire (AAAQ) consisted of a function subscale and a psychosocial subscale, each containing 10 items. The Cronbach's α coefficients of the overall, function subscale and psychosocial subscale were 0.88, 0.78 and 0.78. There were 55 males and 45 females in 100 adult anisometropic amblyopia patients, with a median age of 26 years (range, 18 to 43 years). The age and gender distribution were matched with 100 adult patients with other eye diseases and 100 healthy adults with normal vision (all P>0.05). The mean overall score (28.63±9.18), function subscale score (27.69±9.88) and psychosocial subscale score (29.53±9.90) for adult patients with anisometropic amblyopia were significantly lower compared to adult patients with other eye diseases (71.28±8.14, P<0.01; 65.56±7.81, P<0.01; 76.85±10.76, P<0.01) and visually normal adults (84.54±9.13, P<0.01; 81.70±9.27, P<0.01; 87.38±10.06, P<0.01). Conclusion: The AAAQ meets the requirements for validity and reliability of a HRQOL questionnaire, and can be used to assess the HRQOL of adult patients with anisometropic amblyopia. (Chin J Ophthalmol, 2021, 57: 341-347).

[Association between inflammation activity of left atrial epicardial adipose tissue measured by 18F-FDG PET/CT and atrial fibrillation].

Objective: To explore the association between inflammation activity of left atrial epicardial adipose tissue (LA-EAT) measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and atrial fibrillation (AF). Methods: A total of 78 patients with AF, who underwent 18F-FDG PET/CT in the Nuclear Medicine Department of the Third Affiliated Hospital of Soochow University due to abnormally elevated levels of tumor indicators or malignant tumors from March 2018 to December 2019, were enrolled in this retrospective study. According to the examination date of PET/CT and basic characteristics of AF patients (gender, age), a 1∶1 propensity score matching was used to enroll a non-AF control group (78 patients). The maximum standard uptake value of left atrial epicardial tissue (LA-EAT FDG SUVmax) and total EAT volume (V-EAT) were measured by 18F-FDG PET/CT. Left ventricular ejection fraction (LVEF) and left atrial diameter (LAD) were obtained by echocardiography. Blood lipids and biomarkers of inflammation were measured. The differences of clinical data and EAT-related indicators were compared between the AF group and control group. Logistic multivariate regression analysis was used to determine the related factors of AF. Then the receiver operating characteristic (ROC) curve was used to determine the cutoff value of LA-EAT FDG SUVmax on the diagnosis of AF. Univariate and multivariate logistic regression analysis were used to analyze the relationship between the increase of LA-EAT FDG SUVmax and AF. Results: The age was (66.9±10.2) years and there were 55 males (70.5%) in the AF group. The age was (66.9±8.0) years, and there were 52 males (66.7%) in the control group (both P>0.05). The LAD ((44.2±5.8) mm vs. (35.4±4.4) mm), V-EAT ((122.1±42.0) cm3 vs. (91.6±34.5) cm3), and LA-EAT FDG SUVmax ((1.6±0.3) vs. (1.4±0.2)) values were significantly higher, while LVEF ((60.1±4.7)% vs. (63.9±2.9)%) was lower in the AF group than in the control group (P all<0.001). Multivariate logistic regression analysis showed that LAD (OR=1.340, 95%CI 1.195-1.502), V-EAT (OR=1.016, 95%CI 1.001-1.031), and LA-EAT FDG SUVmax (OR=1.375, 95%CI 1.095-1.723) were positively correlated with AF, LVEF (OR=0.781, 95%CI 0.659-0.926) was negatively correlated with AF(P all<0.05). The area under the ROC curve of LA-EAT FDG SUVmax for diagnosis of AF was 0.680 (95%CI 0.597-0.764, P<0.001), and the best cut-off value was 1.415 with a sensitivity of 65.4% and specificity of 61.5%. After adjusting for high-density lipoprotein cholesterol, LVEF, LAD and V-EAT, LA-EAT FDG SUVmax≥1.415 was independently associated with AF (OR=2.982, 95%CI 1.122-7.926, P=0.010). Conclusions: The inflammatory activity of LA-EAT measured by 18F-FDG PET/CT is an independent risk factor of AF, and the increased inflammatory activity of LA-EAT is positively correlated with AF.