[Diagnosis and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement].

Objective: To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis. Methods: The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted. Results: Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months. Conclusions: Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.

The effect of phacoemulsification on visual function among Filipino cataract patients measured by a validated Filipino translation of Catquest-9SF.

BACKGROUND: This study developed a validated Filipino version of the Catquest-9SF and administered it to cataract patients pre- and post- surgery. METHODS: This is a two-phase, single-center, cross sectional, questionnaire type study. The study included participants decked for surgery who are 18 years and above. Sampling was done purposively. The Catquest-9SF questionnaire was translated into Filipino, according to a standard procedure, and validated. The validated version was administered to the participants before and after unilateral cataract surgery. Data were analyzed using Rasch analysis. RESULTS: Sixty-one patients were enrolled in the study. The preliminary Rasch analysis showed misfit of item 2, which was subsequently excluded from analysis. The remaining eight items showed person separation index of 2.70, reliability coefficient of 0.88, infit of 0.66 to 1.17, outfit of 0.66 to 1.49, observed raw variance explained by measures of 55.3% and eigenvalues of 1.9, 1.4, 1.2, 1.0 and 0.9. There was slightly poor targeting (mean person location 1.24) and multidimensionality but no evidence of differential item functioning (DIF). High internal consistency of items were observed (Cronbach's alpha ≥ 90). Comparison of responses between pre- and post-surgery showed highly significant marginal homogeneity (p < 0.001). CONCLUSION: The Filipino translation of Catquest-9SF, the Catquest-8SF-PH, was highly valid. It showed improved perceived visual outcomes among Filipino patients post-cataract surgery.

[Expression of MSI1 and HER2 in mammary Paget's disease and their correlation with clinicopathological features and prognosis].

Objective: To investigate the expression of MSI1 and HER2 in mammary Paget's disease, and the correlation between the expression levels of MSI1 and HER2 and the clinicopathologic characteristics and prognosis of the patients. Methods: Clinical data and paraffin-embedded specimens of 34 pairs of mammary Paget's disease and underlying breast cancer were collected at the Department of Pathology, Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University from March 2011 to December 2019. Immunohistochemistry was used to detect the expression of MSI1 and HER2 in mammary Paget's disease and the accompanying breast cancer, and to analyze the correlation between the expression levels of MSI1 and HER2 and their clinicopathologic features, as well as their influence on prognosis. Results: In mammary Paget's disease, the positive rate of MSI1 was 91.2% (31/34) and the positive rate of HER2 was 88.2% (30/34); the expression of MSI1 and HER2 was positively correlated (P=0.001, r=0.530). The expression of MSI1 was positively correlated with menopausal status (r=0.372, P=0.030) and lymph node metastasis (r=0.450, P=0.008). HER2 expression was positively correlated with menopausal status (r=0.436, P=0.010), and negatively correlated with ER expression (r=-0.365, P=0.034). The co-expression of MSI1 and HER2 was positively correlated with age (r=0.347, P=0.044) and menopausal status (r=0.496, P=0.003), and negatively correlated with ER expression (r=-0.461, P=0.006). Conclusions: MSI1 and HER2 are highly expressed in mammary Paget's disease and their expression levels are positively correlated. The correlation analysis between clinicopathological features and prognosis suggests that both of them may be involved in the occurrence and development of mammary Paget's disease and are potential therapeutic targets for mammary Paget's disease.

[The IL-6/STAT3 signaling pathway mediated by radiotherapy regulates the expression of PD-L1 in esophageal cancer cells].

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.

[Equol and its enantiomers inhibited urethane-induced lung cancer in mice].

OBJECTIVE: To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice. METHODS: A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison. RESULTS: A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups. CONCLUSION: Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.

[The opportunities and challenges of gynecologic cancer in precision medicine].

In recent years, the diagnosis and treatment of gynecologic cancer have entered a new era with the development of precision medicine. The diagnosis and treatment modes for ovarian cancer, cervical cancer, and endometrial cancer are constantly adjusted. The application of molecular targeted drugs and the progress of surgical concepts and technology have greatly improved the survival of patients with ovarian cancer. Immunotherapy and targeted therapy have become a new hot spot in the treatment of cervical cancer. More clinical research data have been accumulated on the comparison of laparoscopic and open radical hysterectomy in cervical cancer. The surgical management of endometrial cancer has been improved, and molecular diagnostics are increasingly used to guide the diagnosis and treatment of endometrial cancer. Meanwhile, it's necessary to realize the limitations and challenges of precision medicine in gynecologic cancer.

[ALK-positive large B-cell lymphoma with EBV infection or cyclin D1 expression: a clinicopathological analysis of 3 cases].

Objective: To investigate the clinicopathological features and misdiagnosis factors of ALK positive large B-cell lymphoma (ALK+LBCL). Methods: The clinicopathological data of 3 patients with ALK+LBCL in the Department of Pathology, the Affiliated Hospital of Xuzhou Medical University from 2010 to 2021 were collected retrospectively. Immunohistochemistry (IHC) was used for immunophenotyping, in-situ hybridization (ISH) for EBV-encoded RNA (EBER) detection, in-situ fluorescence hybridization (FISH, break-apart probes) for ALK, MYC, and CCND1 translocations. Next-generation sequencing (NGS) was used for the detection of gene fusions and mutations. And clinicopathological features and prognosis of patients were analyzed. Results: Among the 3 ALK+LBCL patients, there were 2 males and 1 female, aged 42, 59, and 39 years, respectively, none of which presented with B symptoms. Case 1 showed systemic lymphadenopathy with elevated serum EBV DNA loading, while cases 2 and 3 presented with extranodal lesions in the nasal and hard palate, respectively. Bone marrow biopsies were performed in cases 1 and 3, and neither showed involvement. Case 1 was at clinical stage Ⅲ while both cases 2 and 3 were at stage Ⅰ, and IPI score ranged 0-1 in all cases. The morphology of these cases was similar. The architecture was effaced by sheets of cohesive large cells growing in extensive infiltration and intra-sinus growth pattern. The neoplastic cells showed immunoblastic or plasmablastic morphology, and large anaplastic cells were easily found. The tumor cells expressed ALK protein cytoplasmically in almost all cells, with ALK gene translocations detected by FISH. Common B-cell and T-cell markers, including CD20, PAX5, CD19, CD2, CD3, CD5, CD7, CD43, CD56, and bcl-2, were negative, while plasmacytic differentiation markers, including CD138, CD38, and MUM1, were positive; CD22, BOB1 and OCT2 were variably expressed. CD10 was strongly expressed only in case 3. All cases were negative for bcl-6 but positive for CD4, perforin, CD30 (partial cells), pSTAT3 (diffusely), and MYC (40%-50%). The Ki-67 index was ranged 60%-70%. MYC translocation was not detected in any case by FISH. In case 1, EBER was strongly positive in>90% of tumor cells. Case 3 was diffusely positive for cyclin D1 but negative for SOX11 expression and CCND1 translocation. All cases harbored ALK fusion genes detected by NGS. In case 1, the fusion partner was TFG, which had not been reported in DLBCL, while in the other 2 cases, ALK fused with the CTCL gene, which was commonly seen in ALK+LBCL. Cases 1 and 3 were treated with ECHOP-based chemotherapy for six cycles and were followed up for 70 and 27 months, respectively, and both achieved complete remission. Conclusions: ALK+LBCL cases with diffuse EBER-positivity reported in this study show TGF as a new fusion partner of ALK in DLBCL, together with cyclin D1 expression. These rare cases are easily confused with EBV positive diffuse large B-cell lymphoma, not otherwise specified (EBV+DLBCL, NOS), cyclin D1 positive diffuse large B-cell lymphoma (cyclin D1+DLBCL) and ALK positive anaplastic large cell lymphoma (ALK+ALCL), resulting in misdiagnosis. Being aware of these rare phenotypes is essential for pathologists to diagnose ALK+LBCL and guide appropriate treatment accurately.

[Comparative study on imaging and clinical results of patellofemoral joint with kinematic alignment and mechanical alignment in total knee arthroplasty].

Objective: To investigate the changes of imaging parameters of patellofemoral joint after kinematic alignment total knee arthroplasty (KA-TKA) and mechanical alignment total knee arthroplasty (MA-TKA) and the effects on clinical outcomes. Methods: A retrospective analysis was performed on 227 patients diagnosed with knee osteoarthritis, 105 males and 122 females, with the age of (68.6±7.2) years (range: 52 to 86 years). The patients underwent unilateral TKA at the Department of Orthopaedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, from January 2020 to July 2021. The patients were divided into the KA-TKA group (n=102) and the MA-TKA group (n=125) according to the alignment method. The Blackburne-Peel index, lateral patellofemoral angle, patellofemoral tilt angle and patellofemoral index of the two groups were recorded before and 6 months after operation. The frequency of lateral patellar retinaculum release, preoperative and postoperative knee range of motion (ROM), and Oxford knee score(OKS) were also recorded. The differences between preoperative and postoperative measurement data of each group were calculated. If the difference was in line with normal distribution, the independent sample t-test or t'-test was used for comparison between the two groups. If it did not conform to normal distribution, Mann-Whitney U test was used. Paired sample t-test was used for comparison before and after treatment. Chi-square test was used for comparation of categorical data between the two groups. Results: After 6 months of operation, the patellar tilt angles of the KA-TKA group and the MA-TKA group were (14.22±3.26)° and (13.35±2.27)°, and the lateral patellar angles were (9.73±4.86)° and (11.91±3.89)°, respectively. The change of lateral patellofemoral angle in the KA-TKA group was significantly less than that in the MA-TKA group ((1.68±4.86)° vs. (4.15±4.88)°, t=3.805, P<0.01). OKS and ROM were improved in the both groups at 6 months after operation (all P<0.05), but there were no statistic significance in preoperative and postoperative difference between the two groups (all P>0.05). The intraoperative lateral patellar retinacular release rate was 14.4% (18/125) in the MA-TKA group and 6.9% (7/102) in the KA-TKA group, with no statistical difference (χ2=3.256,P=0.071). Conclusions: There are greater patella lateral tilt at 6 months postoperatively in the KA-TKA group compared with the MA-TKA group, but this radiographic difference could not show differences of clinical outcomes and postoperative ROM, the frequency of intraoperative lateral patellar retinacular release wouldn't increase. Therefore, KA-TKA does not increase the difficulty of postoperative patellofemoral joint complications and intraoperative lateral patellar release.

[The long-term efficacy of left cardiac sympathetic denervation in long QT syndrome].

Objective: To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD) for long QT syndrome(LQTS) patients with either recurrence on drug therapy intolerance/refusal. Methods: This study was a retrospective cohort study. The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012. This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People's Hospital or Beijing Tongren Hospital. The patients were allocated into 3 groups: high-risk group(n=13, baseline QTc ≥550 ms or symptomatic in the first year of life or highly malignant genetics); intermediate-risk group(n=10, 500 ms≤baseline QTc<550 ms, symptomatic after the first year and without highly malignant genetics); low-risk group(n=5, baseline QTc<500 ms, symptomatic after the first year and without highly malignant genetics). LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery (VATS). Patients were regularly followed up until 20 years after the surgery. Data were collected before and 1 year after surgery and at the last follow-up. Patients' electrocardiograph(ECG), cardiac events and surgery-related complications were recorded. Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes. Results: A total of 28 LQTS patients, aged 20.5 (15.0, 37.5) and underwent LCSD surgery, were enrolled in this study, including 23(82.1%) women. There were 11(39.3%) patients treated with traditional approach while 17(60.7%) with VATS-LCSD. There were 19(67.9%) patients had positive genetic test results, including 4 LQT1, 12 LQT2, 1 LQT1/LQT2 mixed type, and 2 Jervell-Lange-Nielsen (JLN) syndrome. The median follow-up period was 189.3(138.7, 204.9) months. The dropout rate was 10.7%(3/28) while 3 patients in the intermediate-risk group were lost to follow-up. Horner syndrome occurred in 1 patient (in the high-risk group). Sudden cardiac deaths were observed in 3 (12.0%) patients (all in the high-risk group), and 12 patients (48.0%) had syncope recurrences (2 in low-risk group, 3 in intermediate-risk group and 7 in high-risk group). A significant reduction in the mean yearly episodes of cardiac events was observed, from (3.5±3.3) before LCSD to(0.2±0.1) at one year after LCSD and (0.5±0.8) at last follow up(P<0.001). The mean QTc was shortened from (545.7±51.2)ms before the surgery to (489.0±40.1)ms at the last follow-up (P<0.001). Among the 20 patients with basic QTc ≥500 ms and completing the follow-up, the QTc intervals of 11(55.0%) patients were shortened to below 500 ms. The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-, intermediate- and high-risk groups, and the difference was statistically significant (χ²=7.24, log-rank P=0.026). No difference was found in the event free survival rates among LQT1, LQT2 and undefined gene patients (χ²=5.20, log-rank P>0.05). Conclusions: LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up. LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy. However, high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.

Twenty-year changes in mortality rates and underlying causes of death in patients with rheumatoid arthritis-associated interstitial lung disease.

Objectives: Despite recent advances in the treatment of rheumatoid arthritis (RA), few population-based studies have assessed the mortality rates and the underlying causes of death (UCDs) among patients with RA and RA-associated interstitial lung disease (RA-ILD). This study evaluated the trends in mortality rates, demographic characteristics, and UCDs among patients with RA-ILD.Method: Using data from death certificates (1999-2018) from the US Centers for Disease Control and Prevention Multiple Cause of Death files, we explored the trends in mortality rates and UCD for patients with RA and RA-ILD. Moreover, we examined the crude and age-standardized mortality rates (ASMRs) for such patients.Results: Among patients with RA or RA-ILD, ASMR variation decreased over 20 years. The ASMR ratio of RA-ILD to RA decreased by 5.84%. The ASMR for RA and RA-ILD stratified by gender or age group also decreased. The change in the ASMR ratio of RA-ILD to RA trended downwards in women and upwards in men. Arthropathies and ILD were the most frequent UCDs for RA-ILD, while arthropathies and ischaemic heart disease were the most frequent UCDs for RA.Conclusions: Although RA and RA-ILD presented a downward trend in mortality, RA combined with ILD may reduce life expectancy. Specifically, the mortality rate for patients with RA-ILD remained relatively stable during the study period when ILD was the UCD, suggesting the need for active prevention, early diagnosis, and effective management of RA-ILD.

Role of diesel exhaust particles in the induction of allergic asthma to low doses of soybean.

INTRODUCTION: Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of asthma and asthma exacerbation. However, the exact mechanisms inducing asthma to low doses of allergens remain poorly understood. The present study aimed to analyse the immunomodulatory effect of the inhalation of DEP in a mouse model exposed to non-asthmagenic doses of soybean hull extract (SHE). MATERIAL AND METHODS: BALB/c ByJ mice were randomly divided into four experimental groups. Two groups received nasal instillations of saline and the other two groups received 3 mg ml-1 SHE during 5 days per week for 3 weeks. One group in each pair also received 150 µg of DEP in the same instillations 3 days per week. SHE-specific IgE levels, oxidative stress, leukocyte pattern and optical projection tomography (OPT) imaging studies were assessed. RESULTS: Inhalation of SHE and/or DEP increased levels of H2O2 in BAL, while coexposure to SHE and DEP increased SHE-specific IgE levels in serum. Inhalation of SHE alone increased eosinophils, B cells, total and resident monocytes and decreased levels of NK cells, while inhalation of DEP increased neutrophils and decreased total monocytes. Regarding dendritic cells (DC), the inhalation of SHE and/or DEP increased the total population, while the inhalation of SHE alone increased Th2-related DCs (CD11b + Ly6C-) and decreased tolerogenic DCs (CD11b-Ly6C-). However, coexposure to SHE and DEP increased oxidative stress-sensitive DCs (CD11b-Ly6C+) and decreased Th1-related DCs (CD11b + Ly6C+). As regards macrophages, inhalation of SHE and DEP decreased total and alveolar populations. DEP deposition in lung tissue did not differ between groups. CONCLUSION: Coexposure to DEP activates the asthmatic response to low doses of soy by triggering the immune response and oxidative stress.

Impact of feeding n-3 fatty acids to layer breeders and their offspring on concentration of antibody titres against infectious bronchitis, and Newcastle diseases and plasma fatty acids in the offspring.

1. The impact of feeding sources of n-3 fatty acids (FA) to ISA Brown and Shaver White breeders and their offspring on antibody titres and plasma FA profile was examined.2. Breeders were fed either a control diet (CON); CON + 1% microalgae (DMA: Aurantiochytrium limacinum) as a source of docosahexaenoic acid; or CON + 2.6% of a co-extruded mixture of full-fat flaxseed (FFF) as a source of α-linolenic acid. Day-old female offspring were assigned to diets (breeder-offspring): 1) CON-CON, 2) CON-DMA, 3) CON - FFF, 4) DMA - CON, 5) DMA - DMA, 6) FFF - CON or 7) FFF - FFF, followed by a standard layer diet through 18 weeks of age (WOA) to 42 WOA.3. Antibody titres against infectious bronchitis (IBV) and Newcastle disease (NDV) were measured at six days and six WOA, and plasma FA profile was measured at 18 and 42 WOA.4. Pullets from FFF-fed breeders had higher antibody titres against IBV and NDV than pullets fed DMA (P < 0.05). Feeding FFF to offspring increased plasma ∑n-3 FA at 18 and 42 WOA, whereas feeding DMA to offspring reduced ∑n-6 FA at 18 WOA.5. In conclusion, independent of breeder strain, alpha linoleic acid (ALA) and DHA sources showed varied responses. Feeding breeders FFF increased plasma concentration of antibody titres and n-3 FA whereas DMA reduced plasma concentration of ∑n-6 FA.

[Airborne pollens in Wuhan urban area and its correlation with hospital visits of allergic rhinitis patients from 2017 to 2018].

Objective: To investigate the species and concentrations of airborne pollens in Wuhan urban area and their correlation with the number of visits of allergic rhinitis patients. Methods: Retrospective analysis of pollen dispersal characteristics and the number of patients with allergic rhinitis presenting to Tongji Hospital of Huazhong University of Science and Technology in Wuhan city from October 2017 to September 2018, as well as pollen allergen testing results of patients with allergic rhinitis presenting to the Department of Allergy during the same period. Pollen data was collected by a 1-year air sampling conducted in Wuhan City during the same period using the volumetric method. The samples were examined microscopically to identify airborne pollen species and counted, and the concentrations of various pollens were calculated. Information on patients with allergic rhinitis who came to the hospital during the same period was collected, and the correlation between pollen concentration and the number of patient visits was statistically analyzed using Pearson correlation analysis. Results: A total of 35 types of airborne pollen were collected from October 2017 to September 2018. The dominant pollens in spring were Moraceae (68.46%, 1 042/1 522), Pendula (12.22%, 186/1 522) and Cupressaceae (2.30%, 35/1 522); in summer and autumn, the dominant pollens were Artemisia (3.81%, 58/1 522), Humulus (4.01%, 61/1 522) and Ambrosia (0.59%, 9/1 522). The peak number of visits for allergic rhinitis patients occurred in March-April and July-September, both exceeding 2 200 visits and reaching a maximum of 2 545 visits. There was a very weak correlation between the number of visits and the total pollen concentration (r=0.17, P=0.001). The average monthly pollen skin prick test positive rate of patients with allergic rhinitis was highest in March-May, exceeding 40% with a maximum of 45.73%, and there was a significant correlation between the positive pollen skin prick test positive rate and the average monthly pollen concentration (r=0.62, P=0.031). Conclusions: Pollen species and concentrations fluctuated continuously with time in Wuhan urban area, with peak pollen dispersal in spring from March to April and in autumn from August to September. The number of visits to patients with allergic rhinitis and the positive pollen skin prick test positive rate increased accordingly during the peak pollen concentration periods.

[Levels of human milk oligosaccharides in breast milk of mothers delivering preterm infants of different gestational ages and their effects on early growth and development].

Objective: To investigate the human milk oligosaccharides (HMOs) levels in breast milk of mothers delivering preterm infants and their effects on the early growth and development of infants. Methods: In this prospective cohort study, full-term and preterm newborns whose parents decided to breastfeed were recruited from Peking University Third Hospital between December 1, 2017 and November 30, 2018. The preterm infants were divided based on their gestational ages into extremely preterm (<28 weeks), very preterm (28-31+6 weeks) and moderate to late preterm (32-36+6 weeks) groups. Breast milk was collected from mothers at 7, 14, 28 and 120d postpartum. 368 breast milk samples were collected from 125 mothers in this study, including 54 mothers of full-term infants, 23 mothers of moderate to late preterm infants, 39 mothers of very preterm infants, and 9 mothers of extremely preterm infants. Ultra-performance liquid chromatography-mass spectrometer (UPLC-MS/MS) was used to determine the concentration of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), 3'-sialyllactose (3'SL), A-tetrasaccharide (P1), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose Ⅱ (LNFP-Ⅱ) and lacto-N-fucopentaose Ⅴ (LNFP-Ⅴ). Secretor status of mothers was defined as 2'-fucosyllactose (2'FL) concentration in colostrum and transitional milk greater than 200 µg/mL. Weight gain and the occurrence of allergic diseases of infants were collected at 120 d(4 months) postpartum. The chi-square test or the Fisher's exact test was used for the comparison of categorical data between groups; Kruskal-Wallis test and Wilcoxon rank sum test were used for comparison of continuous data between groups. Nemenyi test was used for multiple comparison. Results: 79.2% (99/125) of the mothers were secretor. There were no statistical differences between groups in the secretor status of mothers (χ²=1.31,P>0.05). The total concentration of HMOs peaked at 1-2 weeks postpartum. Compared to the preterm milk, the HMOs from the term milk was trending downwards at an earlier time. In the breast milk of secretor mothers on 28 d, total concentration of HMOs significant differed among the three groups of preterm milk and the term milk, with the median value of 4 587.09,4 615.25,5 277.44,5 476.03 µg/mL, respectively (Kruskal-Wallis χ²=8.1234,P=0.044). When analyzed by the median weight gain of the infants (low vs high weight gain) at 4 months postpartum, 2'FL was significantly lower in the high weight gain group at 7 d (1 818.04 µg/mL vs 2 181.67 µg/mL, W=1 386,P=0.018), while LNT & LNnT were significantly higher (1 182.36 µg/mL vs 1 053.62 µg/mL, W=816,P=0.044). The level of 3FL at 120 d was significantly affected by presence of allergic disease in infants, breast milk from mothers of infants with allergic disease had lower 3FL than those from mothers of infants without allergic disease (256.17 µg/mL vs 286.18 µg/mL, W=564,P=0.026). Conclusions: The overall profiles of HMOs in breast milk of mothers delivering preterm infants was basically the same as that of mothers delivering term infants; individual HMOs play a role in weight gain and the development of allergic diseases in preterm infants, but the mechanism is unclear and needs further study.

Shear stress-induced MMP1 and PDE2A expressions in coronary atherosclerosis.

AIM: Biomechanical stress plays an essential role in coronary atherosclerosis (CAS), however, inter-relations between mechanical conditions and gene expressions remain unclear. METHODS: We constructed finite element model of CAS to map human wall shear stress (WSS). Biopsy aortic tissue samples were obtained from 3 CAS patients. Gene expression pattern in CAS was analyzed by GEO datasets. Immunofluorescence staining and western blot confirmed protein expression and localization. RESULTS: Peak WSS was significantly increased in the vessel stenosis of CAS at 0.25 s (mean 55.1 Pa). Analyses results of GSE76275 showed matrix metalloproteinases1 (MMP1) and phosphodiesterase-2A (PDE2A) up-regulation in endothelial shear responsiveness, which was further validated and localized in vascular endothelial cells, smooth muscle cells and other cells by double immunofluorescence staining. Western blotting assay demonstrated up-regulation of MMP1 and PDE2A expression dependent on the WSS. CONCLUSIONS: MMP1 and PDE2A up-regulations rely on increased WSS in development and risk of CAS, suggesting that their elevation may be potential target for diagnosis and treatment (Fig. 3, Ref. 28).

[Expression of VHL, VEGF and HIF-1α in endolymphatic sac tumors].

Objective: To investigate the expression of von Hippel-Lindau (VHL), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α) in endolymphatic sac tumor (ELST) and its clinical significance, and to analyze its association with VHL gene mutation. Methods: Twenty-four cases of ELST, which were surgically resected and diagnosed by pathological examination in Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China during 2012-2020, were recruited as the ELST group, and 24 cases of otitis media diagnosed in the same hospital were selected as the control group. The expression of VHL, VEGF, and HIF-1α was assessed using EnVision immunohistochemical staining and compared between the ELST and control groups. Sanger sequencing was performed to detect the VHL mutation status in 24 ELSTs. The correlations among VHL, VEGF and HIF-1α expression were analyzed. The associations of VHL, VEGF and HIF-1α expression with age of onset, gender, tumor size, bone invasion and clinical stage in ELST were also analyzed. Results: The expression rate of VHL in the ELST group was significantly lower than that in the control group (P<0.05), but the expression rates of VEGF and HIF-1α in the ELST group were significantly higher than those in the control group (P<0.05). VHL expression was inversely correlated with VEGF and HIF-1α expression. The expression of VEGF and HIF-1α was associated with bone invasion and clinical stage (P<0.05), but the expression of VHL, VEGF and HIF-1α had no significant associations with the age of onset, gender, or tumor size of ELST (P>0.05). Conclusions: The expression of VHL is decreased while that of VEGF and HIF-1α increased in ELST. Expression of VHL is inversely correlated with that of VEGF and HIF-1α. The expression of VEGF and HIF-1α is correlated with bone invasion and clinical stage. Thus, VEGF and HIF-1α may be therapeutic targets of ELST.

[A comparative study of the retroperitoneal cavity established by the modified Hasson in urology].

Objective: To examine the safety and complications of two methods of establishing retroperitoneal cavity in urology. Methods: Totally 83 patients undergoing retroperitoneal laparoscopic surgery in Department of Urology, Shanxi Bethune Hospital from January 2020 to June 2021 were analyzed retrospectively. There were 47 males and 36 females, aged (48.3±11.3) years (range: 35 to 71 years). Forty-three cases in Hasson group(the first Trocar channel was selected at the junction of the 12th rib and the posterior axillary line or lumbar triangle), 40 cases in modified Hasson group(the first Trocar channel is selected at 1.5 cm above the iliac crest on the mid-axillary line). The t test, χ² test, and Fisher exact test were used to compare the surgical safety indicators and complications of the two groups of patients. Results: There was no statistical difference between the two groups in gender, age, body mass index, waist length, and height (P>0.05). The comparison of safety indicators, included the time from skin incision to establishment of the retroperitoneal cavity and the amount of bleeding from the cavity were statistical difference between the two groups (P<0.05). Compared to that in Hasson group, the time from skin incision to establishment of the abdominal cavity in modified Hasson group was shorter ((8.56±2.64) minutes vs. (5.32±1.36) minutes, t=6.949, P<0.01), the blood loss of establishment was less ((15.32±6.09) ml vs. (9.85±3.55) ml, t=4.951, P<0.01). In terms of complication indicators, the incidence of Trocar hernia and the number of subcutaneous emphysema in modified Hasson group were lower than that in Hasson group (20.9% (9/43) vs. 2.5% (1/40), P=0.015, 18.6% (8/43) vs. 2.5% (1/40), P=0.030). Conclusions: The modified Hasson group is a safe method of establishing retroperitoneal cavity. The technique is simple and fast. It provides urologists with a more effective and easy-to-implement option with fewer complications.

Immunorelated gene polymorphisms associated with acute myeloid leukemia.

Although the pathogenesis of acute myeloid leukemia (AML) is still unknown, accumulating evidence has revealed that immune response plays a vital part in the pathogenesis. Here, we investigated the involvement of 21 single nucleotide polymorphisms (SNPs) of immunorelated genes, including cytokines [interleukin (IL)-2, IL-4, IL-9, IL-12A, IL-22, interferon (IFN-α) and transforming growth factor (TGF)-ß1], transcriptional regulatory genes (TBX21, STAT1, STAT3, STAT5B, STAT6, GATA3, FOXP3 and IRF4) and others (IL2RA, IL6R, NFKBIA) in 269 AML in-patients and 200 healthy controls. Furthermore, we analyzed the relationship between the SNPs and clinical characteristics. Immunorelated SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. All the SNPs in healthy controls were consistent with Hardy-Weinberg equilibrium. All final P-values were adjusted by Bonferroni multiple testing. Our results showed that IL-22 (rs2227491) was significantly associated with the white blood cell (WBC) counts. Signal transducer and activator of transcription 5B (STAT-5B) (rs6503691) showed a close relationship with the recurrent genetic abnormalities in patients with AML. We verified the negatively independent effect of age and risk of cytogenetics on overall survival (OS). More importantly, the GG genotype of IL-12A (rs6887695) showed a negative impact on AML prognosis independently. Furthermore, the relative expression of IL-12 was decreased in GG genotype, no matter under a co-dominant or recessive model. However, no correlation was observed between the SNPs mentioned above and disease susceptibility, risk stratification and survival. Our findings suggest that immunorelated gene polymorphisms are associated with prognosis in AML, which may perform as novel inspection targets for AML patients.

Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery.

BACKGROUND: Delirium is common in elderly patients after surgery and is associated with poor outcomes. This study aimed to investigate the impact of intraoperative dexmedetomidine on the incidence of delirium in elderly patients undergoing major surgery. METHODS: This was a randomized double-blind placebo-controlled trial. Elderly patients (aged 60 years or more) scheduled to undergo major non-cardiac surgery were randomized into two groups. Patients in the intervention group received a loading dose of dexmedetomidine 0·6 µg/kg 10 min before induction of anaesthesia followed by a continuous infusion (0·5 µg per kg per h) until 1 h before the end of surgery. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of delirium during the first 5 days after surgery. Delirium was assessed with the Confusion Assessment Method (CAM) for non-ventilated patients and CAM for the Intensive Care Unit for ventilated patients. RESULTS: In total, 309 patients who received dexmedetomidine and 310 control patients were included in the intention-to-treat analysis. The incidence of delirium within 5 days of surgery was lower with dexmedetomidine treatment: 5·5 per cent (17 of 309) versus 10·3 per cent (32 of 310) in the control group (relative risk (RR) 0·53, 95 per cent c.i. 0·30 to 0·94; P = 0·026). The overall incidence of complications at 30 days was also lower after dexmedetomidine (19·4 per cent (60 of 309) versus 26·1 per cent (81 of 310) for controls; RR 0·74, 0·55 to 0·99, P = 0·047). CONCLUSION: Intraoperative dexmedetomidine halved the risk of delirium in the elderly after major non-cardiac surgery. Registration number: ChiCTR-IPR-15007654 ( www.chictr.org.cn).

ANTECEDENTES: El delirio después de la cirugía es frecuente en los pacientes de edad avanzada y se asocia con malos resultados. El objetivo de este estudio fue investigar el impacto de la administración intraoperatoria de dexmedetomidina en la incidencia de delirio en pacientes mayores sometidos a operaciones de cirugía mayor. MÉTODOS: Se trataba de un ensayo aleatorizado, doble ciego y controlado con placebo. Un total de 620 pacientes mayores (60 años o más) fueron programados para ser sometidos a intervenciones (no cardiacas) de cirugía mayor y se aleatorizaron a dos grupos. Los pacientes en el grupo de intervención recibieron una dosis de carga de dexmedetomidina (0,6 µg/kg, 10 minutos antes de la inducción anestésica) seguida de una infusión continua (0,5 µg/kg/h) hasta 1 h antes de la finalización de la cirugía. Los pacientes del grupo control recibieron el mismo volumen de suero salino siguiendo la misma pauta. El resultado principal era la incidencia de delirio durante los primeros 5 días postoperatorios. Para la valoración del delirio se utilizó el método para la evaluación de la confusión (Confusion Assessment Method, CAM) en pacientes no intubados y el CAM-UCI para los pacientes intubados. RESULTADOS: En total, 309 pacientes que recibieron dexmedetomidina y 310 del grupo control se incluyeron en el análisis por intención de tratar. La incidencia de delirio durante los primeros 5 días tras la cirugía fue inferior en presencia de tratamiento con dexmedetomidina que en ausencia del mismo: 5,5% (17/309) versus 10,3% (32/310); riesgo relativo (RR) 0,53, i.c. del 95% 0,30-0,94, P = 0,026. La incidencia global de complicaciones a los 30 días excluyendo el delirio también fue inferior en presencia que en ausencia de tratamiento con dexmedetomidina (19,4% (60/309) versus 26,1% (81/301), RR 0,74, i.c. del 95% 0,55-0,99, P = 0,047). CONCLUSIÓN: La administración intraoperatoria de dexmedetomidina reduce la presencia de delirio en los pacientes mayores tras cirugía mayor no cardiaca.

Ageing affects the proliferation and mineralization of rat dental pulp stem cells under inflammatory conditions.

AIM: To comparatively evaluate changes in the proliferation and mineralization abilities of dental pulp stem cells (DPSCs) from juvenile and adult rats in a lipopolysaccharide (LPS)-induced inflammatory microenvironment to provide a theoretical basis for the age-related differences observed in DPSCs during repair of inflammatory injuries. METHODOLOGY: DPSCs were isolated from juvenile (JDPSCs) and adult rats (ADPSCs), and senescence-associated ß-galactosidase staining was used to compare senescence between JDPSCs and ADPSCs. Effects of LPS on JDPSCs and ADPSCs proliferation were investigated by cell counting kit-8 assays and flow cytometry. Alizarin red staining, quantitative reverse transcription polymerase chain reaction and Western blot assay were used to examine the effects of LPS on mineralization-related genes and proteins in JDPSCs and ADPSCs. Immunohistochemistry was used to compare interleukin-1ß (IL-1ß) and osteocalcin (OCN) expression in the pulpitis model. Unpaired Student's t-tests and one-way anova were used for statistical analysis. RESULTS: DPSCs were isolated from juvenile and adult rat dental pulp tissues. At low concentrations (0.1-1 µg mL-1 ), LPS significantly promoted the proliferation of JDPSCs (P < 0.01) and ADPSCs (P < 0.01 or P < 0.05), with the effect being stronger in JDPSCs than in ADPSCs. In addition, mineralized nodules and the expression of mineralization-related genes (OCN, DSPP, ALP, BSP) increased significantly after stimulation with LPS (0.5 µg mL-1 ) in JDPSCs and ADPSCs (P < 0.01 or P < 0.05), and JDPSCs displayed a more obvious increase than ADPSCs. Western blots revealed OCN and ALP expression levels in JDPSCs treated with LPS were significantly upregulated (P < 0.05); meanwhile, ALP expression in ADPSCs increased slightly but significantly (P < 0.05), and OCN expression was not affected. Finally, IL-1ß expression was significantly higher (P < 0.05) and OCN expression was significantly lower (P < 0.05) in the inflamed dental pulp of adult rats than in juvenile rats. CONCLUSIONS: A certain degree of inflammatory stimulation promoted the proliferation and mineralization of DPSCs; however, this effect declined with age. The DPSCs of adult donors in an inflammatory microenvironment have a weaker repair ability than that of juvenile donors, who are better candidates for tissues damage repair.