A Mendelian randomization study of the effect of selenium on autoimmune thyroid disease.

OBJECTIVE: The impact of selenium on autoimmune thyroid disease (AITD) is a subject of ongoing debate. This study aimed to analyze the causal correlations of selenium with autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves' disease (GD) by Mendelian randomization (MR). MATERIALS AND METHODS: Single nucleotide polymorphisms related to selenium, AIT, AIH, and GD were sourced from the IEU Open GWAS project and FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. Horizontal pleiotropy was examined using the MR-Egger intercept, heterogeneity was evaluated with Cochran's Q test, and the robustness of the results was confirmed via leave-one-out sensitivity analysis. RESULTS: The MR analysis revealed that selenium did not exhibit a causal relationship with AIT (OR 0.993, 95% CI 0.786 to 1.108, p=0.432), AIH (OR 1.066, 95% CI 0.976 to 1.164, p=0.154), or GD (OR 1.052, 95% CI 0.984 to 1.126, p=0.138). Moreover, the MR-Egger intercept and Cochran's Q test demonstrated the absence of horizontal pleiotropy or heterogeneity in these results (p>0.05). Sensitivity analysis affirmed the robustness of these results. CONCLUSIONS: This MR analysis concluded that selenium was not linked to AIT, AIH, or GD risk. Therefore, indiscriminate selenium supplementation is not advisable for AITD patients without concurrent selenium deficiency.

[Application of modified urethral separation method in artificial urethral sphincter implantation and its influence on intraoperative urethral pressure profilometry].

Objective: To explore the application of modified urethral separation method in artificial urethral sphincter (AUS) implantation in patients with stress urinary incontinence (SUI), and its influence on the results of urethral pressure profilometry. Methods: A prospective collection of clinical data was conducted on 25 patients with stress urinary incontinence who underwent modified urethral separation method in AUS implantation and underwent urethral pressure profilometry in Beijing Hospital, Beijing Jishuitan Hospital Affiliated to Capital Medical University and the Second Hospital Affiliated to Tianjin Medical University from March 2019 to June 2023. The improved urethral separation method was to borrow part of the white membrane tissue of the cavernous body while freeing the dorsal side of the cavernous body of the urethra. The circumference of the urethra, sleeve size, and urethral pressure were recorded, the patient's autonomous urinary control before and after surgery and the changes of the international consultation on incontinence questionnaire-short form (ICI-Q-SF) score, incontinence quality of life questionnaire (I-QoL) score, urinary frequency score, nocturia score were compared. Follow-up was conducted in the clinic or by telephone at 1, 3, 6, and 12 months after activation of the device, and once a year thereafter. Local skin status and urine control were assessed, residual urine volume was measured by ultrasound and subjective score scale was completed. Results: All patients were male, aged 27-85 (65.8±15.7) years old. The circumference of the cuff used in this study was 4.0 cm in 4 patients (16.0%), 4.5 cm in 16 patients (64.0%), 5.0 cm in 4 patients (16.0%), and 5.5 cm in 1 patient (4.0%). Among them, the urethral circumference matched the cuff size in 14 cases (56.0%), the urethral circumference was smaller than the cuff size in 4 cases (16.0%), and the urethral circumference was larger than the cuff size in 7 cases (28.0%). Preoperative urodynamic examination showed that the maximum urethral pressure (MUP) was (78.0±25.9) cmH2O, (1 cmH2O=0.098 kPa) and the maximum urethral closure pressure (MUCP) was (53.4±26.6) cmH2O. The MUP of AUS device in the inactivated state was (88.0±26.5) cmH2O, which was not significantly higher than that before operation (P>0.05). The MUCP was (68.2±24.5) cmH2O, which was significantly higher than that before operation (P<0.05). The MUP and MUCP of the AUS device in the activated state were (146.6±25.2) cmH2O and (123.0±28.3) cmH2O, which were significantly higher than those before surgery and in the inactivated state (both P<0.001). All patients in the group reached the social urinary control standards at the first month of device activation. During a follow-up period of 2-50 months, 22 patients (88.0%) used the initial AUS device and all met social urinary control standards. The AUS device was replaced in 1 case. One patient died of cerebrovascular accident. One patient removed the device due to complications. The number of pads [M (Q1, Q3)] used in 25 patients before and after operation was 4.5 (3.0, 6.5) and 1 (0, 1) respectively, with statistically significant differences (P<0.001). ICI-Q-SF score, I-QoL score, urinary frequency score and nocturia score of 25 patients were significantly improved after surgery (all P<0.05). The incidence of postoperative complications was 20.0% (5/25), including 2 cases of painless hematuria, 1 case of infection, 1 case of urethral erosion, and 1 case of dysuria. Except for one patient who experienced urethral erosion and had his sleeve removed, the remaining four patients regained social urination control with active support treatment, and no symptoms recurred until the last follow-up. Conclusion: The modified urethral separation method has no significant effect on urethral pressure in patients with SUI, and can increase the volume of peri-urethral tissue in the cuff, thereby reducing the risk of intraoperative urethral injury and the incidence of postoperative urethral erosion.

[Clinicopathological characteristics of gastric SMARCA4-deficient undifferentiated/rhabdoid carcinoma].

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of gastric SMARCA4-deficient undifferentiated carcinoma, and to discuss the daily diagnostics of this entity and analyze its prognosis. Methods: The cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed at the Department of Pathology, Peking University Cancer Hospital, China from January 2010 to August 2022 were collected. The histological sections were reviewed, the immunohistochemical results and clinicopathological features were analyzed, and relevant literature was reviewed. Results: Pure foci of undifferentiated carcinoma were seen in 7 cases, and 1 case was accompanied by a moderately differentiated tubular adenocarcinoma component. Undifferentiated carcinoma foci showed similar sheet-like or solid diffuse growth pattern, medium-sized tumor cells characterized by 1-2 nucleoli, and abundant cytoplasm and rhabdoid appearance. The average patient age was 65±8 years. Six patients were male and 2 were female. Immunohistochemical staining showed that undifferentiated carcinoma of all 8 tumors were negative for SMARCA4 (BRG1). Among 7 patients who underwent SMARCA2 (BRM) and SMARCB1 (INI1) staining, 4 cases showed loss of BRM expression, 2 cases showed weakly positive staining, and 1 case was diffusely positive, but all 7 cases were diffusely strong positive for INI1. The neuroendocrine marker, synaptophysin, was weakly positive in 5 cases, while CgA and CD56 were negative in 8 cases. Ki-67 index was more than 70%. Two cases were mismatch repair deficient and showed the loss of MLH1/PMS2 expression, while 1 case showed only MSH2 loss. PD-L1 staining showed that combined positive score (CPS)≥1 in 4 cases (CPS ranging from 1 to 55) and CPS<1 in the other 3 cases. Four patients had clinical stage Ⅳ disease. Two of them died within 3 months after diagnosis. Conclusions: Gastric SMARCA4-deficient undifferentiated carcinoma/rhabdoid carcinoma is a rare group of highly malignant tumors with a poor prognosis. Loss of the core subunit of SWI/SNF complex may be associated with the development of dedifferentiated histological pattern and aggressive tumor progression, which may be more frequently accompanied with mismatch repair deficiency.

[A case of skin ulcers secondary to extensive burns caused by flame and heavy metal-containing hydrothermal fluids].

On May 13, 2020, a 56-year-old man with extensive burns caused by flames and heavy metal-containing hydrothermal fluids was admitted to the General Hospital of Western Theater Command. After being admitted to the hospital, most of the burn wounds healed after treatments such as debridement, expansion, skin grafting, anti-shock, anti-infection, fluid replacement, and wound dressing change, etc. However, in the middle and late stages of treatment, the patient's burn wounds gradually showed repeated skin ulceration and inflammation. After excluding the cause of physical, bacterial infection and others, IgG4-related skin diseases was finally diagnosed by histopathological examination of tissue biopsy and concentration measurement of IgG4 in interstitial fluid, and the condition was improved after hormone treatment. This suggests that extensive burns may lead to the occurrence of autoimmune skin diseases. For the diagnosis of such diseases, it is necessary to combine clinical manifestations, serological examinations, and histopathological biopsy, etc. to avoid diagnostic pitfalls and draw correct conclusions.

Evaluation of miR-429 as a novel serum biomarker for pancreatic ductal adenocarcinoma and analysis its tumor suppressor function and target genes.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer. Various microRNAs have been identified to play an important role in PDAC. The study aimed to explore the role of miR-429 in PDAC. PATIENTS AND METHODS: The expression and prognostic value of miR-429 were first analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Next, miR-429 expression was evaluated in the tissues and serum of 90 patients with PDAC. CCK8, SRB, wound healing and transwell assays were used to determine the effect of miR-429 on the proliferation, invasion, and migration of PDAC cells, respectively. Weighted gene co-expression network analysis (WGCNA), correlation analysis, TargetScan, and miRDB databases were used to screen and identify the target genes of miR-429. RESULTS: The results revealed that the expression of miR-429 was downregulated in PDAC tissues and the serum compared with those in normal tissues and the serum of healthy volunteers, respectively. The decreased expression of miR-429 was significantly associated with shorter overall survival. The overexpression of miR-429 significantly inhibited the proliferation, invasion, and migration of PDAC cells. Potential target genes of miR-429 were identified using WGCNA and bioinformatics analysis, and the results showed that cadherin 11 (CDH11), inositol polyphosphate-4-phosphatase type I (INPP4A), laminin gamma 1 (LAMC1), low density lipoprotein receptor-related protein 1 (LRP1), and quaking (QKI) were potential target genes of miR-429 in PDAC. Lower expression of CDH11 and QKI was associated with a more favorable prognosis in patients with PDAC. The overexpression of miR-429 could inhibit the expression of CDH11 and QKI. A nomogram model, involving miR-429, CDH11, and QKI, was subsequently constructed to determine their ability to accurately predict overall and disease-free survival in patients with PDAC. CONCLUSIONS: Taken together, miR-429 is involved in the development and progress of PDAC. MiR-429 could be recommended as a prognostic biomarker and therapeutic indicator in PDAC diagnosis.

[Three dimensional nephrometry system for partial nephrectomy: Our initial exploration].

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm3 and (33.0±36.4) cm3, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION: Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.

[Evaluation of the prognostic value of MIPSS70-plus in Chinese patients with primary myelofibrosis].

Objective: To evaluate the prognostic value of MIPSS70-plus in Chinese patients with primary myelofibrosis (PMF) . Methods: A total of 113 Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, Log-rank test, and Cox proportional hazard regression model were performed to evaluate the prognostic factors. The likelihood ratio test was used to evaluate the predictive power between MIPSS70-plus and DIPSS systems. Results: The median age of the Chinese patients was 55 (range: 20-70) years, including 71 males and 42 females. According to the standard of MIPSS70-plus system, 99 patients (79.6% ) had a favorable karyotype and 23 patients (20.4% ) had an unfavorable karyotype. JAK2V617F in 55.8% (n=63) , CALR exon9 in 17.7% (including 15 CALR type 1 and 5 CALR type 2, n=20) , MPLW515 in 4.4% (n=5) , and triple negative (no detectable JAK2, MPL, and CALR mutations) in 22.1% of patients in our cohort were found by target-specific next-generation sequencing approach. At least one high-molecular risk mutations were presented in 45.1% (n=51) of patients, with ASXL1 in 38.9% (n=44) , SRSF2 in 7.1% (n=8) , IDH1/2 in 4.4% (n=5) , and EZH2 in 3.5% (n=4) of patients. A total of 28 patients (26.7% ) were in low risk, 20 (19.0% ) in intermediate risk, 41 (39.0% ) in high risk, and 16 (15.3% ) in very-high risk categories, which were delineated for the MIPSS70-plus model. A 2-year OS was 100% in low risk, 89.7% (95% CI 76.2% -100.0% ) in intermediate risk, 64.8% (95% CI 47.0% -82.6% ) in high risk, and 35.0% (95% CI 10.3% -59.7% ) in very-high risk categories, which had a significant difference (P<0.001) . A significantly higher predictive power for survival of the MIPSS70-plus group was observed compared with the DIPSS group (P=0.001, -2 log-likelihood ratios of 86.355 vs 95.990 for the MIPSS70-plus and DIPSS systems, respectively) . Conclusion: The MIPSS70-plus had significantly higher predictive power than the DIPSS.

[Incidence and etiological analysis of abnormal cardiac uptake in patients underwent oncologic PET/CT imaging].

Objective: To investigate the incidence, location and etiology of abnormal cardiac uptake in patients underwent oncologic 18F-fluorodeoxyglucose positron emission tomography/computed tomography(PET/CT) imaging. Methods: The 18F-FDG PET/CT images of 2000 consecutive patients with suspected or diagnosed malignancy in Beijing Chaoyang Hospital from January 2014 to September 2016 were retrospectively analyzed. Fasting time was more than 12 hours before imaging, and fasting blood glucose level before 18F-FDG injection was less than 6.7 mmol/L. Focal uptake in the non-basal and non-papillary regions of the left ventricle, uptake in the right ventricle exceeding uptake in the left ventricle, and uptake in the atrium higher than that of the blood pool (when uptake of left ventricle was zero or low) were defined as abnormal, and all abnormal uptake was visually determined by experienced nuclear medicine physicians. General clinical data and the results of cardiac examination were collected to explore the incidence, location and etiology of cardiac diseases. Results: There were 138 patients with history of diabetes (6.90%), 228 patients with history of cardiovascular disease (11.40%) out of the 2 000 patients ((60.5±13.2) years, 1 117 male (55.85%)). The number and proportion of patients with malignancy, benign lesions, diseases of unknown etiology were 939 (46.95%), 484 (24.20%), 557 (28.85%), respectively. Abnormal cardiac uptake was detected in 145 patients (7.3%). The proportion of abnormal uptake in left ventricle, right ventricle and atrium was 52.4% (76 cases), 12.4% (18 cases), 35.2% (51 cases), respectively. Of the 76 individuals who had abnormal uptake in left ventricle, 25 cases (32.9%) were caused by coronary artery disease, and other causes included hypertrophic cardiomyopathy and myocardial damage caused by chemotherapy drugs, etc. Of the 18 cases who had abnormal uptake in right ventricle, 14 cases (14/18) were caused by pulmonary hypertension. In addition, 20 out of the 51 cases (39.3%) with abnormal uptake in atrium suffered from atrial fibrillation. Seventy-one patients with abnormal cardiac uptake (49.0%) had no clear manifestation and evidence of heart disease before imaging. Conclusions: The abnormal 18F-FDG uptake on oncologic PET/CT is not rare. The most common site of abnormal uptake is left ventricle, coronary artery disease, pulmonary hypertension and atrial fibrillation are common causes of abnormal 18F-FDG uptake.

[A clinical analysis of 14 cases of prostatic stromal tumor of uncertain malignant potential].

OBJECTIVE: To investigate the clinical and pathologic characteristics, diagnosis, treatment, prognosis and survival of prostatic stromal tumor of uncertain malignant potential. METHODS: Overall 14 patients with prostatic stromal tumor of uncertain malignant potential were treated from October 2008 to April 2020, the patient age ranged from 27 to 78 years (mean 54 years). The disease duration was 1 to 180 months (mean duration of 46 months). The clinical manifestations mainly included urinary obstructive symptoms and urethral irritating symptoms. The tumors were located in the peripheral zone or the transition zone. Digital rectum examination indicated prostatic tumor. Serum prostatic specific antigen level was always normal or elevated. Transrectal ultrasonography and magnetic resonance imaging indicated prostatic tumor. Magnetic resonance imaging in showed large, round, well-defined masses, which were diffusely heterogeneous signal on T2 weighted imaging. Following the administration of intravenous contrast medium, the lesion had diffuse and heterogeneous enhancement. RESULTS: In the study, 3 cases underwent prostate biopsy, 2 cases underwent transurethral resection of the prostate, 9 cases underwent radical excision or transurethral resection of the prostate with definite diagnosis of pathologic features. Under the light microscope, the interstitial cells of stromal tumor of uncertain malignant potential were overgrowth and fusiform cells showed some degree of pleomorphism, nuclei with few mitotic figures, and necrosis was not often seen. Immunohistochemical staining showed that prostate specific antigen was negative, while vimentin was positive in the tumor tissue, CD34, progesterone receptor and smooth muscle actin were positive in the majority, and Ki67 positive index was 1%-20% (mean 6%). Twelve cases were followed-up, and the time of survival varied from 10 to 96 months (mean 65 months), two cases were lost to the follow-up, one case died of disease at the end of 10 months, nine cases were free of disease recurrence after surgery, two cases underwent more transurethral resection of the prostate due to local recurrence. CONCLUSION: STUMP is a very rare tumor of the specialized prostatic stroma with an unpredictable clinical behavior. The clinical manifestations, transrectal ultrasonography and magnetic resonance imaging are valuable for the diagnosis of prostatic stromal tumor of uncertain malignant potential. Its definite diagnosis depends on pathological examination. Up to now, early surgery and combined therapy are effective treatments for prostatic stromal tumor of uncertain malignant potential.

[Application of urethral pressure profilometry in artificial urinary sphincter implantation].

Objective: To investigate the changes of maximum urethral pressure (MUP) and maximum urethral closure pressure (MUCP) after artificial urethral sphincter (AUS) implantation and their prognostic value. Methods: The clinical data of patients who had undergone AUS implantation in multiple medical centers between March and July 2019 were retrospectively analyzed. Data of urethral pressure profilometry, pad usage, related scores and complications related to surgery were collected and compared. The primary endpoint was social continence (defined as 0-1 pad/d) 1 month after activation of the pump. Results: A total of five male patients were included in this study. Two underwent transurethral resection of the prostate for benign prostatic hyperplasia, two underwent radical prostatectomy for prostate cancer, and one underwent urethral reunion, urethral stricture dilatation and cystostomy due to trauma from traffic accident. All patients had different degrees of urinary incontinence. The results of preoperative urethral profilometry test showed that the MUP of five patients were 52, 53, 88, 32, and 66 cmH(2)O(1 cmH(2)O=0.098 kPa), respectively, and the MUCP were 17, 52, 62, 27, and 40 cmH(2)O, respectively. AUS implantation was performed. The intraoperative urethral pressure profilometry showed that the MUP were 53, 113, 50, 77, and 89 cmH(2)O in the inactivated state, and the MUCP were 50, 97, 31, 71, and 51 cmH(2)O, respectively. In the activated state, the MUP were 112, 174, 193, 121, and 120 cmH(2)O, and the MUCP were 109, 160, 175, 114, and 92 cmH(2)O, respectively. All patients met the social continence (0-1 pad/d) criterion. No complications were reported during the follow-up. Conclusions: The relationship between the range of intraoperative urethral pressure and the effect of urinary control can be gained by measuring the specific values of MUP and MUCP during AUS implantation and the post-operative effects, which provides as a data basis for standardizing AUS implantation.

MiR-92b inhibits proliferation and invasion of lung cancer by targeting EZH2.

OBJECTIVE: To verify that miR-92b inhibits proliferation and invasion of lung cancer by targeting EZH2. MATERIALS AND METHODS: The expression levels of miR-92b and EZH2 in human bronchial epithelial cell line BEAS-2B and human lung cancer cell line (A549, NCI-H23, NCI-H358, NCI-H1975, PC-9) were detected, and miR-92b mimic, sh-EZH2 expression vector, and plasmid blank vector (blank group) were constructed. Blank group, miR-92b mimic, miR-92b mimic+sh-EZH2 group (combined group) were set up, MTT and transwell were used to detect the proliferation and invasion ability of A549 and NCI-H23 cells, and fluorescein report verified the regulatory relationship of miR-92b to EZH2. RESULTS: The expression level of miR-92b in A549, NCI-H23, NCI-H358, NCI-H1975, and PC-9 cells was lower than that in BEAS-2B cells (p<0.05). The expression level of EZH2 was higher than that of BEAS-2B cells (p<0.05). A549 and NCI-H23 cells were selected for transfection. After that, the expression level of miR-92 in miR-92b mimic, combined group A549 and NCI-H23 cells was higher than that in blank group (p<0.05), and miR-92b mimic had no difference with joint group (p>0.05). The expression level of EZH2 in cells of miR-92b mimic, blank group A549, and NCI-H23 was lower than that of combined group (p<0.05), and miR-92b mimic was lower than that of blank group (p<0.05). After the overexpression of miR-92b, pmirGLO-EZH2-3'UT Wt luciferase activity decreased significantly (p<0.05) but had no effect on pmirGLO-EZH2-3'UTR Mut Luciferase activity (p>0.05). Cell proliferation ability and invasion ability of A549 cells and NCI-H23 cells in miR-92b mimic group were lower than those in blank group (p<0.05), while those in combined group were higher than those in miR-92b mimic group (p<0.05). CONCLUSIONS: MiR-92b inhibits proliferation and invasion of lung cancer cells through targeted inhibition of EZH2, which is a potential target for future treatment of lung cancer.

A New Mutation Genotype of K218T in Myosin-5 Confers Resistance to Phenamacril in Rice Bakanae Disease in the Field.

In 2017 and 2018, a total of 294 Fusarium fujikuroi isolates were collected from bakanae-diseased rice plants in Jinhua, Shaoxing, and Jiaxing in Zhejiang Province, China. Phenamacril sensitivity of these isolates was determined by the 50% effective concentration value or minimum inhibitory concentration methods. Our results indicated that the phenamacril resistance frequency of F. fujikuroi increased from 18% in 2017 to 47% in 2018, and rice plants infected with F. fujikuroi-resistant isolates could not be protected effectively with 50 mg/liter of phenamacril. Phenamacril-resistant F. fujikuroi isolates obtained from rice fields showed stable resistance, because their fitness levels (i.e., mycelial growth, sporulation, and pathogenicity) were similar to the phenamacril-sensitive isolates. In addition to the point mutation at codon 219 in the myosin-5 gene that conferred resistance to phenamacril, our results also showed another point mutation at codon 218 (AAG→ACG) in myosin-5 that also conferred resistance to phenamacril. In this study, we found rapid development and persistence of diversified genotypes of phenamacril resistance, highlighting the importance of proper use of phenamacril in rice fields. Our results may also help researchers develop new fungicides or new control strategies using combinations of different fungicides in the control of phenamacril-resistant F. fujikuroi isolates.

[Genetic characteristics and prognostic values of RAS mutations in patients with myelofibrosis].

Objective: To explore the genetic characteristics, clinical features, and prognostic values of RAS mutations in patients with myelofibrosis (MF) . Methods: We analyzed 112-gene targeted sequencing data from 226 patients who had a diagnosis of either primary myelofibrosis (PMF) or post-polycythemia vera/post-essential thrombocythemia (post-PV MF and post-ET MF) from December 2011 to December 2019. A retrospective analysis of the genetic characteristics, clinical features, and prognosis of RAS mutations was performed. Results: Among 266 patients diagnosed PMF or post-PV/ET MF, RAS mutations were found in 14 (6.2%) cases, including 9 (4.0%) cases of NRAS mutations, 8 (3.5%) cases of KRAS mutations, and 3 (1.3%) cases of both NRAS and KRAS mutations. All of the NRAS mutations were located in codons 12 and 13. The median VAFs of RAS mutations were significantly lower than those of the driver mutations, confirming that they represent sub-clonal events that are acquired during the disease course. SETBP1, SRSF2, and MPL tended to be clustered with RAS mutations. Patients with RAS mutations had a higher number of additional oncogenic mutations (median, 3.36 vs 1.17, P<0.001) . RAS mutations had a statistically significant association with elevated monocyte cell counts (P=0.003) , lower platelet counts (P=0.026) , higher bone marrow blasts (P=0.022) , splenomegaly (P=0.005) , and very high-risk (VHR) karyotype abnormality percentage (P=0.031) . In univariate analysis, the OS of patients with NRAS mutations were significantly inferior in the entire MF and PMF cohorts (P=0.001, P=0.008) . In a multivariate model, NRAS retained an independent negative prognostic factor in PMF. Conclusion: RAS gene mutations were constantly related to elevated monocyte cell counts, lower platelet counts, higher bone marrow blasts, and VHR karyotype abnormality percentage that usually defined high-risk disease and often occurred as sub-clonal events. NRAS mutation is an independent poor prognostic factor in PMF.

[Detection of EDA gene mutation and phenotypic analysis in patients with hypohidrotic ectodermal dysplasia].

OBJECTIVE: To detect the ectodysplasin A (EDA) gene mutation in patients with hypohidro-tic ectodermal dysplasia (HED), and to analyze the distribution pattern of missing permanent teeth and the systemic manifestation of HED patients with EDA gene mutation. METHODS: Twelve HED families were enrolled from clinic for genetic history collection, systemic physical examination and oral examination. Peripheral blood or saliva samples were collected from the probands and the family members to extract genomic DNA. PCR amplification and Sanger sequencing were utilized to detect the EDA gene variations, which were compared with the normal sequence (NM_001399.5). The functional impact of EDA gene variants was then evaluated by functional prediction of mutation, conservation analysis and protein structure prediction. The pathogenicity of each EDA gene variation was assessed according to the stan-dards and guidelines of the American College of Medical Genetics and Genomics (ACMG). The systemic phenotype and missing permanent tooth sites of HED patients with EDA gene mutations were summarized, and the missing rate of each tooth position was analyzed and compared. RESULTS: Eight out of twelve HED families were identified to carry EDA gene mutations, including: c.164T>C(p.Leu55Pro); c.457C>T (p.Arg153Cys); c.466C>T(p.Arg156Cys); c. 584G>A(p.Gly195Glu); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys). Among them, c.164T>C(p.Leu55Pro); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys) were novel mutations. The HED patients with EDA gene mutations in this study were all male. Our results showed that the average number of missing permanent teeth was 13.86±4.49, the average number of missing permanent teeth in the upper jaw was 13.14±5.76, the missing rate was 73.02%. And in the lower jaw, the average number of missing permanent teeth was 14.57±3.05, the missing rate was 80.95%. There was no significant difference in the number of missing teeth between the left and right sides of the permanent dentition (P>0.05). Specifi-cally, the maxillary lateral incisors, the maxillary second premolars and the mandibular lateral incisors were more likely to be missing, while the maxillary central incisors, the maxillary and mandibular first molars had higher possibility of persistence. CONCLUSION: This study detected novel EDA gene pathogenic variants and summarized the distribution pattern of missing permanent teeth of HED patients, thus enriched the variation and phenotype spectrum of EDA gene, and provided new clinical evidence for genetic diagnosis and prenatal consultation.

[The predicting value of the 8th edition of American Joint Committee on Cancer staging manual in mucinous breast cancer].

Objective: The current study aimed to evaluate the predictive performances of anatomic staging system (AS) and prognostic staging system (PS) proposed in the 8th edition American Joint Committee on Cancer (AJCC) staging manual in patients with pure mucinous breast cancer (PMBC). Methods: Clinicopathologic features and follow-up information were collected from a total of 3628 patients with PMBC. Breast cancer-specific survival (BCSS) were compared among patients in different stage groups. Likelihood ratio (LR) χ(2), Akaike information criterion (AIC) and Harrell's concordance index (C-index) were used to evaluate the predictive performances of AS and PS in PMBC. Results: In PMBC, BCSS was associated with tumor size (P=0.002), lymph node status (P=0.002), grade(P=0.003), PR status(P=0.017)and the receipt of radiation. Compared to AS, 1326 patients (37.54%) underwent stage change after applying PS, with 6.50% upstaged and 37.04% downstaged. There were significant differences in BCSS among patients of different stages under the AS and PS (P<0.001). However, PS was not superior to AS in predicting prognosis (AS vs PS, LR χ(2): 16.41 vs 17.5; AIC: 357.44 vs 358.35; C-index, 0.72 vs 0.73, P=0.667). Conclusions: Both of AS and PS proposed in the 8th edition American Joint Committee on Cancer (AJCC) staging manual were predictive factors in patients with PMBC. Compared with AS, the PS did not show superiority in prognosis prediction among patients with PMBC.

[The association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma].

Objective: To investigate the association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma (ESCC) in China. Methods: From March 2014 to September 2018, ESCC patients from three hospitals (the Affiliated Hospital of Medical College of Shantou University, Shantou Central Hospital in Southern Chaoshan area and First Affiliated Hospital of Zhengzhou University in Northern Taihang Mountain) were selected as a case group; non-esophageal patients who had a physical examination were selected as a control group. The case and control group were paired by age (±5 years) and a 1:1 ration. A total of 1 528 subjects were enrolled including 764 patients in the case group and 764 patients in the control group. About 3-5 ml venous blood samples were collected, and the erythrocyte glutathione reductase activity coefficient (GRAC) was measured to assess the whole blood riboflavin level. A multivariate conditional logistic regression model was used to analyze the association between the GRAC and the risk of ESCC. The association between the GRAC and the prognosis of ESCC was analyzed by using Cox proportional risk regression model based on 288 patients with complete survival data. They were divided into two groups, the high GRAC group (GRAC≥7.87) group and the low GRAC group (GRAC<7.87) according to the strongest correlation between the total survival time, survival outcome and GRAC (GRAC=7.87). Results: Among the 1 528 patients, 958 patients were from Southern Chaoshan area, including 479 patients in the case group with an average age about (59.90±9.34) years and 479 patients in the control group with an average age about (59.55±8.77) years. Other 570 patients were from Northern Taihang Mountain area, including 285 patients in the case group with an average age (58.39±5.19) years and 285 patients in the control group with an average age about (58.74±4.57) years. The multivariate conditional logistic regression showed that the OR (95%CI) of the GRAC and the risk of ESCC was 1.009 (0.998-1.019). The Cox proportional hazard regression model analysis showed that the HR (95%CI) of the high GRAC group was 1.712 (1.034-2.824) compared with the low GRAC group in the 50-70 years group. Conclusion: The whole blood riboflavin level might not be associated with the occurrence of ESCC. The high whole blood riboflavin level would be more beneficial to the prognosis of ESCC patients aged 50-70 years.

[Evaluating inferior vena cava wall invasion in renal cell carcinoma tumor thrombus with MRI].

OBJECTIVE: To evaluate the diagnostic performance of MRI for the assessment of inferior vena cava (IVC) wall invasion by IVC thrombus in patients with renal cell carcinoma (RCC). METHODS: We retrospectively collected patients who underwent radical nephrectomy and thrombectomy for RCC between 2010 and 2018 at Peking University First Hospital. All the patients underwent imaging on a 1.5 Tesla or 3.0 Tesla MRI scanner. Fifty-six patients met the inclusion criteria. Preoperative imaging was reviewed by two radiologists blinded to details of the patient's surgical procedure and histopathology. Two radiologists measured the maximum anterior-posterior diameter and coronal diameters of the IVC and renal vein, and the craniocaudal extent of tumor thrombus, and evaluated the MRI features of IVC thrombus, including occlusion of the IVC lumen, the margin of the tumor thrombus (smooth vs. irregular), contact of the IVC thrombus and IVC wall, and altered signal of the IVC wall. Univariable and multivariable associations of clinical and radiographic features with IVC wall invasion were evaluated by Logistic regression. RESULTS: Of the 56 patients [male: 43, female: 13, mean age: (55.64±0.43) years], 17 (30.36%) were detected with IVC wall invasion, and most were clear cell carcinoma. Tumor thrombus with IVC wall invasion showed an increase in length of IVC thrombus [(7.91±3.59) cm vs. (5.94±3.57) cm, P=0.049], and more features of complete occlusion of the IVC lumen (P=0.002), irregular margin of the IVC thrombs (P=0.005), contact of the IVC thrombus and IVC wall (P=0.001), and altered signal of the low-intensity vessel wall (P<0.001), with a sensitivity of 94.12% and a specificity of 79.49%. CONCLUSION: The present study indicates that MRI could be a means of evaluating RCC with IVC wall invasion, and the combination of tumor thrombus length and subjective impression of IVC wall invasion achieved a high sensitivity and specificity for diagnosis.

[Experimental study on the effect of Yiqi Wenyang Decoction on nasal mucosa infiltration of NK cells in mice with allergic rhinitis].

Objective: To observe the effect of Yiqi Wenyang Decoction on the infiltration and activation of NK cells in nasal mucosa of mouse model with allergic rhinitis (AR), and to explore the potential mechanism for effective intervention of AR with Yiqi Wenyang Decoction. Methods: Fourty-eight mice were randomly divided into blank group, model group, low, medium and high dose of Yiqi Wenyang Decoction group and Cetirizine group, with 8 rats in each group. After modeling of AR, the model group was filled with 0.9% sodium chloride solution. Yiqi Wenyang Decoction groups of each dose were given different concentrations of Yiqi Wenyang Decoction water extract, while the Cetirizine group was given aqueous solution of Cetirizine. The behavior, morphological changes of nasal mucosa and infiltration of NK cells in nasal mucosa were observed. The levels of IL-4 and INF-γ in nasal lavage fluid were measured. Besides, the drug safety was observed by acute toxicity test. Results: In the respect of behavioral scoring, middle and high dose of Yiqi Wenyang Decoction group were superior to the model group (number of sneezing: q value was 7.189, 8.748, respectively; number of scratching nose: q value was 12.074, 14.560, respectively; all P<0.05). In middle and high dose of Yiqi Wenyang Decoction group, the infiltration of NK cells and nasal lavage fluid IL-4 levels were lower than those in model group (IOD: q value was 10.073, 12.322, respectively; IOD/Area: q value was 10.954, 14.073, respectively; IL-4: q value was 4.705, 6.801, respectively; all P<0.05). There was no significant difference in nasal lavage fluid of INF-γ among each group (Fv=1.166, P>0.05). In acute toxicity test, no obvious poisoning symptoms and death occurred in mice. Conclusion: Yiqi Wenyang Decoction can control the nasal symptom, reduce the local NK cell infiltration of nasal mucosa and inhibit the expression of the 2-type cytokines released by NK cells, which may be related with the potential mechanism of effective intervention of AR with Yiqi Wenyang Decoction.