Multiparametric MRI-based radiomics nomogram for predicting malignant transformation of sinonasal inverted papilloma.

AIM: To investigate the feasibility of a radiomics nomogram model for predicting malignant transformation in sinonasal inverted papilloma (IP) based on radiomic signature and clinical risk factors. MATERIALS AND METHODS: This single institutional retrospective review included a total of 143 patients with IP and 75 patients with IP with malignant transformation to squamous cell carcinoma (IP-SCC). All patients underwent surgical pathology and had preoperative magnetic resonance imaging (MRI) and computed tomography (CT) sinus studies between June 2014 and February 2022. Radiomics features were extracted from contrast-enhanced T1-weighted images (CE-T1WI), T2-weighted images (T2WI), and apparent diffusion coefficient (ADC) maps. The least absolute shrinkage and selection operator (LASSO) were performed to select the features extracted from the sequences mentioned above. Independent clinical risk factors were identified by multivariate logistic regression analysis. Radiomics nomogram was constructed by incorporating independent clinical risk factors and radiomics signature. Based on discrimination and calibration, the diagnostic performance of the nomogram was evaluated. RESULTS: Twelve radiomics features were selected to develop the radiomics model with an area under the curve (AUC) of 0.987 and 0.989, respectively. Epistaxis (p=0.011), T2 equal signal (p=0.003), extranasal invasion (p<0.001), and loss of convoluted cerebriform pattern (p=0.002) were identified as independent clinical predictors. The radiomics nomogram model showed excellent calibration and discrimination (AUC: 0.993, 95% confidence interval [CI]: 0.985-1.00 and 0.990, 95% CI: 0.974-1.00) in the training and validation sets, respectively. CONCLUSION: The nomogram that the combined radiomics signature and clinical risk factors showed a satisfactory ability to predict IP-SCC.

Recurrent ZNF83-E293V Mutation Promotes Bladder Cancer Progression through the NF-κB Pathway via Transcriptional Dysregulation of S100A8.

Urothelial carcinoma (UC) is the predominant form of bladder cancer. Significant molecular heterogeneity caused by diverse molecular alterations brings about large variations in the response to treatment in UC. An improved understanding of the genetic mechanisms underlying the development and progression of UC is essential. Through deep analysis of next-generation sequencing data of 99 UC patients, we found that 18% of cases had recurrent somatic mutations in zinc finger protein gene zinc finger protein 83 (ZNF83). ZNF83 mutations were correlated with poor prognosis of UC. We also found a hotspot mutation, p.E293V, in the evolutionarily well-conserved region of ZNF83. ZNF83-E293V increased tumor growth and reduced the apoptosis of UC cells compared to wild-type ZNF83 both in vitro and in mice xenografted tumors. ZNF83-E293V activated nuclear factor κB (NF-κB) more potently than did the wild-type protein owing to its decreased transcriptional repression for S100A8. The NF-κB inhibitors could pharmacologically block the tumor growth in mice engrafted with ZNF83-E293V-transfected UC cells. These findings provide a mechanistic insight and a potential therapeutic strategy for UC, which established a foundation for using the ZNF83-E293V mutation as a predictive biomarker of therapeutic response from NF-κB inhibitors.

MRI-based radiomics for the diagnosis of triple-negative breast cancer: a meta-analysis.

AIM: To analyse the diagnostic value of magnetic resonance imaging (MRI)-based radiomics for triple-negative breast cancer (TNBC) by conducting a meta-analysis. MATERIALS AND METHODS: A comprehensive search was performed to identify relevant English articles concerning the MRI-based radiomics diagnosis of TNBC (from the date of database establishment to November 2021). The pooled sensitivity (SEN), pooled specificity (SPE), positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR) with 95% confidence interval (CI), summary receiver operating characteristic (SROC) curve and area under the curve (AUC) for the accuracy of MRI-based radiomics in the diagnosis of TNBC were calculated. The I2 test was used to assess heterogeneity and the source of heterogeneity was investigated by performing a meta-regression analysis. Publication bias was assessed using Deeks' funnel plot asymmetry test. RESULTS: Six studies (1,223 patients) met the eligibility criteria. The pooled sensitivity and specificity were 0.72 and 0.91, respectively. The LR+ of the malignant ultrasonic features was 8.0, and the LR- was 0.31, revealing that MRI-based radiomics exhibited excellent ability to confirm or exclude TNBC. SROC curves showed that the AUC of the MRI-based radiomics diagnosis of TNBC was 0.88, indicating that MRI-based radiomics has good diagnostic value for TNBC. CONCLUSIONS: MRI radiomics is an excellent diagnostic tool with high specificity for the diagnosis of TNBC.

CT and MRI features of extraocular muscle granular cell tumour: preliminary experience in eight cases.

AIM: To characterise the computed tomography (CT) and magnetic resonance imaging (MRI) features, in particular the functional MRI characteristics, of extraocular muscle granular cell tumours (GCTs). MATERIALS AND METHODS: The CT (n=6) and MRI (n=8) features of eight extraocular muscle GCTs cofirmed at histopathology were analysed retrospectively. The imaging findings were evaluated with emphasis on the location, size, margin, shape, extent, bony change, internal architecture, enhancement pattern, and extent of lesions. Based on diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, the apparent diffusion coefficient (ADC) value of six lesions and time-intensity curve (TIC) of one lesion were reviewed. RESULTS: Immunohistochemistry revealed strong positivity for S-100 protein and a low Ki-67 index (2-5%) in all cases. Most of the lesions (7/8) were confined to the muscle belly with an ovoid shape. All of the tumours were isodense to cerebral grey matter and showed homogeneously mild enhancement on CT images. All lesions were hypointense to cerebral grey matter on T2-weighted imaging (T2WI) and showed homogeneously marked enhancement on contrast-enhanced T1-weighted imaging (T1WI). All lesions showed a hypo- or isointense signal on DWI images with a high b-value. The mean ADC of six lesions was (0.72 ± 0.14) × 10-3 mm2/s. The TIC of the case examined using DCE-MRI showed a plateau pattern (type II). CONCLUSION: A well-defined oval mass confined to the muscle belly with a hypointense signal on T2WI, homogeneously marked enhancement on contrast-enhanced T1WI, hypo- or isointense signal on DWI, and low ADC value is highly suggestive of a GCT.

Endolymphatic sac tumour: exploring the role of CT and MRI features in the diagnosis of 22 cases.

AIM: To explore the role of imaging features in the diagnosis of endolymphatic sac tumour (ELST). MATERIALS AND METHODS: Twenty-two patients with ELST confirmed at histopathology were included in this retrospective study. All patients underwent computed tomography (CT) and magnetic resonance imaging (MRI) examinations, including diffusion-weighted imaging (DWI; n=18) and dynamic contrast-enhanced (DCE) MRI (n=3). The imaging features of this series were analysed. RESULTS: All lesions appeared as irregular soft-tissue mass lesions located in the middle and posterior margin of the petrous bone. At CT, the normal vestibular aqueduct structure disappeared. Multiple osteoid tissues were present inside the tumour, and destructive bone changes had a "honeycomb" pattern. Twenty cases were accompanied by the incomplete thin bony peripheral rim along the medial margin. On both T1-weighted imaging (WI) and T2WI, all lesions showed hyperintense, hypointense, and isointense mixed signal intensity. Scattered peripheral hyperintensities were found in all cases on T1WI. The mean apparent diffusion coefficient (ADC) value of 18 lesions was (1.35 ± 0.13) × 10-3 mm2/s, which was similar to that of masseter muscles. On enhanced T1WI, all lesions had significant heterogeneous enhancement, and the vascular flowing-void effect was seen in larger lesions (≥1.5 cm). The time-signal intensity curve (TIC) showed a plateau type in all three cases. CONCLUSIONS: The imaging features of ELST, including its location, bone destruction form, MRI signal intensity, and enhancement pattern, are helpful to improve the diagnostic accuracy of this rare tumour.

Differentiation of malignant from benign orbital tumours using dual-energy CT.

AIM: To investigate the diagnostic accuracy of dual-energy computed tomography (DECT)-derived iodine concentration (IC), effective atomic number (Zeff), and spectral attenuation information for differentiating malignant and benign orbital tumours. MATERIALS AND METHODS: Data from 41 patients with orbital tumours from November 2019 to March 2021 were analysed retrospectively. Each patient underwent contrast-enhanced DECT using a 128-section dual-source computed tomography (DSCT) system. Dual-energy information, including IC, normalised iodine concentration (NIC), Zeff, virtual monoenergetic images (VMIs) reconstructed from 40 to 120 keV and slope (k) value were determined. Quantitative measurement of DECT parameters was undertaken by two independent radiologists blinded to clinical data. Differences in parameters were assessed using independent sample t-test. Diagnosis performance was calculated by the receiver operating characteristic (ROC) curve analysis. Radiation doses of conventional CT and DECT were compared by paired t-tests. RESULTS: Forty-one patients with histopathologically confirmed tumours were enrolled, including 10 malignant cases and 21 benign cases. Malignant orbital tumours exhibited significantly greater IC, NIC, Zeff, CT attenuation of VMIs at 40-105 keV, and k values compared to benign orbital tumours (p<0.05). In ROC analyses, 40 keV VMI demonstrated the highest diagnostic performance of single parameters (area under the ROC curve [AUC], 0.940), and combined parameters achieved the best performance (AUC, 0.971; sensitivity, 90%; specificity, 93.55%). Radiation doses were significantly reduced in DECT than conventional CT (p<0.001). CONCLUSIONS: Quantitative DECT analysis can be a useful technique, which yields excellent diagnostic accuracy, in the differentiation of malignant and benign orbital tumours with low radiation dose.

[The study of relationship between occupational stress and sleep quality of video display terminals].

Objective: To investigate the sleep quality of video operators in Shenzhen, and explore the relationship between sleep quality and occupational stress and different work and life habits. Methods: In December 2020, a cluster sampling method was used to investigate 791 video operators in Shenzhen from June to December 2020 who were engaged in printing, design, IT and other industries. The Pittsburgh Sleep Quality Index Scale was used to investigate the sleep quality of video operators, and the Job Content Questionnaire was used to investigate the occupational stress of video operators, The Pay Return Imbalance Questionnaire was used to investigate the pay return imbalance of video operators. The measurement data conforming to the normal distribution shall be expressed by mean±standard deviation, and t-test, analysis of variance and linear correlation analysis shall be adopted according to the type of independent variable. Those that do not conform to the normal distribution are described by the median M (Q(1), Q(3)), and two sample Wilcoxon test is used according to the binary data of independent variable type. Kruskal Wallis test was used for multi classification data, and Spearman rank correlation was used for single factor analysis for ordinal classification data. The counting data were analyzed by chi square test or Fisher exact probability method. Logistic regression was used for multivariate analysis. Results: the pittsburgh sleep quality index was 4.76±2.86. 499 of them had high sleep quality. 292 people had low sleep quality, accounting for 36.91% (292/791). Compared with the low sleep quality group, the high sleep quality group had lower work requirement scores (13.48±1.77), higher autonomy scores (24.08±3.33), higher social support scores (23.95±3.08), lower pay scores (16.11±2.63), higher return scores (31.11±3.65), and lower internal input scores (14.98±2.55). There were statistically significant differences between the two scales in each dimension index group (P<0.05). Multi factor unconditional logistic regression analysis showed that high education level (OR=1.57, 95%CI=1.26~1.98, P<0.05), occupational stress (OR=1.69, 95%CI=1.21~2.36, P<0.05), and high pay and low return (OR=1.41, 95%CI=1.01~1.96, P<0.05) were the main influencing factors of sleep quality. Conclusion: The occurrence of occupational stress in video operators is a risk factor for low sleep quality, which should be paid enough attention.

Sinonasal synovial sarcoma: evaluation of the role of radiological and clinicopathological features in diagnosis.

AIM: To explore the value of radiological and clinicopathological features in the diagnosis of sinonasal synovial sarcomas (SS). MATERIALS AND METHODS: Six patients with sinonasal SS were studied retrospectively using computed tomography (CT; n=6) and magnetic resonance imaging (MRI; n=4). The radiological and clinicopathological findings in this series were reviewed. RESULTS: Three lesions were located, in both the nasal cavity, and the paranasal sinuses; one was located in the nasal cavity and nasopharynx, and the remaining two were located restrictively within the nasal cavity. An aggressive nature (invasion of adjacent structure) was found in four cases. At CT, lesions were found with isodensity with calcification mainly in the peripheral areas. Bony changes were visible in all cases. Five cases showed marked heterogeneous enhancement, and three cases contained necrotic or cystic areas. At MRI, haemorrhage was observed in three cases. All cases demonstrated the "triple sign", and two high-grade SS showed a "cobblestone-like" appearance on T2-weighted imaging (WI). All time-signal intensity curves (TICs) were of the washout type. The mean apparent diffusion coefficient (ADC) values of the two high-grade cases were lower than those of the low-grade or intermediate-grade cases. Histopathologically, all but one was of the monophasic type. During the 8-40 month period of follow-up, recurrence occurred in four cases. CONCLUSIONS: A sinonasal tumour exhibiting characteristic calcification and bony change, together with haemorrhage, "triple sign" or "cobblestone-like" appearance, should engender a diagnosis of SS.

[Clinical factors of pathological complete response after neoadjuvant chemoradiotherapy in rectal cancer].

Objective: To explore the feasibility of clinical factors to predict the pathological complete response after neoadjuvant chemoradiotherapy in rectal cancer. Methods: A retrospective analysis was performed on clinical factors of 162 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy in the General Hospital of People's Liberation Army from January 2011 to December 2018.According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) group and non-pathological complete response group (non-pCR group) to check the predictive clinical factors for pCR. Results: Twenty-eight cases achieved pCR after neoadjuvant chemoradiation (17.3%, 28/162). Univariate analysis showed that patients with higher differentiation (P=0.024), tumor occupation of the bowel lumen≤1/2 (P=0.006), earlier clinical T stage (P=0.013), earlier clinical N stage (P=0.009), the time interval between neoadjuvant chemoradiotherapy and surgery>49 days (P=0.006), and maximum tumor diameter≤5 cm (P=0.019) were more likely to obtain pCR, and the differences werestatistically significant. Multivariate analysis showed that tumor occupation of the bowel lumen≤1/2 (P=0.01), maximum tumor diameter≤5 cm (P=0.035), and the interval>49 days (P=0.009) were independent factors in predicting pCR after neoadjuvant therapy. Conclusion: Tumor occupation of the bowel lumen, maximum tumor diameter, and the time interval between neoadjuvant chemoradiotherapy and surgery can predict the pCR in rectal cancer.

[Clinical value of suspicious calcification in the diagnosis and surgical treatment of breast lesions using contrast-enhanced spectral mammography].

Objective: To evaluate clinical value of suspicious calcification in the diagnosis and surgical treatment of breast lesions using contrast-enhanced spectral mammography. Methods: Ninty-four patients who underwent CESM with suspicious calcification on the low-energy(LE) images in Third Affiliated Hospital of Soochow University from April 2017 to April 2019 were collected.All patients were female, with an average age of 51 years (26 to 89 years).All patients underwent biopsy or surgery to obtain pathological results. Two experienced radiologists provide BI-RADS classification for LE images and CESM. To assess pairwise agreement between BI-RADS classification on CESM and LE images among readers, kappa test were calculated. Using pathology results as the gold standard,the diagnostic efficacy of LE images and CESM were analyzed by receiver operating characteristic (ROC)curve, and Z test was used to compare the areas under the ROC curves (AUC) among them, calculated the sensitivity, specificity. The intraclass correlation coefficient (ICC) was used to analyze the consistency of the maximum image diameter and pathological diameter of malignant lesions. Two experienced radiologists provided the preferred surgical treatment (breast conservation therapy versus mastectomy) for all malignant cases according the imaging findings. McNemars test was used to compare the difference between surgical decision making and final surgical procedure. Results: One hundred and three lesions were found in 94 patients, in which 49 were benign and 54 were malignant.Overall agreement on BI-RADS classification between LE imaging and CESM among readers was substantial (0.74 vs 0.86), CESM was higher than LE images. The sensitivity of LE images and CESM were 80.4%, 96.2%, specificity was 75.0%, 94.0%, AUC were 0.810, 0.960 respectively. There was significant difference of the AUC between LE images and CESM (Z=3.66, P<0.01). The ICC of malignant lesions measured on LE images and CESM and histopathological results were 0.86 and 0.96, respectively. Based on LE images, 44.4%(24/54) of patients recommended BCT, 55.6%(30/54) of patients recommended mastectomy, the difference was statistically significant (P=0.008). Based on CESM, 27.8%(15/54) of patients recommended breast conservation therapy, 72.2%(39/54) of patients recommended mastectomy,there was no significant statistically difference with the final surgical procedure (P=0.125). Conclusion: CESM has a high diagnostic accuracy for suspicious calcification of breast. And its accuracy in assessing malignant lesion size is higher, which can provide a basis for preoperative surgical decision making.

[A questionnaire survey for gout management in physicians in Beijing].

Objective: To provide helpful continued medical education (CME) for physicians and improve gout treatment, we conducted a questionnaire survey to investigate physicians' knowledge in nine districts of Beijing. Methods: A questionnaire survey including ten gout-related questions was conducted among 298 physicians in Beijing. Demographic data and previous gout CME experience were collected. Chi-square test or Student's t test, univariate analysis and logistic regression analysis were used to evaluate the relevant factors of physicians' knowledge level. Results: A total of 250 valid copies were collected including 127 from community service centers (CSC), 123 from tertiary hospitals. The correct answer rate of gout etiology, pathogenesis and attack symptoms were over 70% in both groups. 45.5% (56/123) CSC doctors and 57.4% (66/115) tertiary doctors answered right drugs to control acute gout attack (P=0.067). Only 42.3% (52/123) in CSC and 53.4% (63/118) in hospitals chose allopurinol as a urate-lowering drug (ULT), while 46.3% (57/123) and 32.2% (38/118) doctors considered colchicine as a ULT drug (P=0.084) respectively. Near half doctors considered that gout patients should take long-term ULT [40.5% (51/126) vs. 57.6%(68/118)respectively, P=0.007]. Univariate analysis showed that CME training could improve gout-related knowledge in CRC doctors. Conclusion: Most CSC doctors generally understand basic knowledge of gout, while confusion of treatment is still significant. CME especially including standard gout treatment should be performed by doctors in tertiary hospitals.

[Influence of low dose perfluorooctanoate acid exposure to the cell proliferation, migration and invasion of the human muscle rhabdomyosarcoma cell line].

Objective: This study aimed to explore the effect of perfluorooctanoate acid (PFOA) on the proliferation, migration and invasion of the human muscle rhabdomyosarcoma RD cell line and its related mechanisms. Methods: RD cells were cultured and exposed to PFOA of different concentrations with 6-72 hours. The cell viability was assessed by cell counting kit-8 (CCK-8) assay. Wound healing and transwell filter assay were used to evaluated the migration and invasion ability of the RD cells respectively. The cell cycles were detected by Flow cytometry. Quantitative real-time PCR and Western blot were used to quantify the mRNA and protein expression difference of related genes, respectively. Results: CCK-8 assay showed that, after treated the RD cell with different dose of PFOA for 72 h, low dose PFOA (1,10,50, 100 µmol/L) promotes the proliferation of RD cells while high dose PFOA (250, 500 mol/L) inhibits the proliferation (P<0.001). Flow cytometry showed that compared with the control group, there was no significant difference in G0/G1 phase, while cells in S phase deceased and G2/M phase cells increased after treated with PFOA (50 µmol/L) for 72 h. The relative proportions of S and G2/M were significantly different between the two groups (P<0.01). The results of qPCR showed that the mRNA relative expression of CDK2 of the control group and the PFOA (50 µmol/L) group were 0.97±0.07 and 2.64±0.11 respectively, and there was a significant difference (t=12.60, P<0.001); The mRNA relative expression of cyclin E2 of the control group and the PFOA (50 µmol/L) group were 1.33±0.17 and 3.35±0.22 respectively, and there was a significant difference (t=7.42, P<0.001); The results of Western blot showed that the protein relative expression of CDK2 of the control group and the PFOA (50 µmol/L) group were 0.35±0.01 and 0.84±0.03 respectively, and there was a significant difference (t=14.60, P<0.001); The protein relative expression of cyclin E2 of the control group and the PFOA (50 µmol/L) group were 0.67±0.04 and 0.86±0.01 respectively, and there was a significant difference (t=4.88, P<0.01); There was no significant difference in the mRNA and protein expression of p21 and p53 between the PFOA and control group (P>0.05). The wound healing rate of the PFOA (50 µmol/L) group was faster than that of the control group, and the relative migration area of the PFOA group was larger accordingly (P<0.001). After PFOA (50 µmol/L) treated, the number of the cell through the membranes was much more than the control group (t=54.40, P<0.001), which means PFOA significantly stimulated the invasion ability of the RD cells. The results of qPCR showed that the mRNA relative expression of vimentin of the control group and the PFOA (50 µmol/L) group were 0.71±0.03 and 2.53±0.16 respectively, and there was a significant difference (t=11.00, P<0.001); The mRNA relative expression of MMP2 of the control group and the PFOA (50 µmol/L) group were 1.09±0.04 and 10.73±1.20 respectively, and there was a significant difference (t=8.04, P<0.001). The results of Western blot showed that the protein relative expression of vimentin of the control group and the PFOA (50 µmol/L) group were 0.55±0.06 and 0.81±0.01 respectively, and there was a significant difference (t=4.50, P<0.05). The protein relative expression of cyclin E2 of the control group and the PFOA (50 µmol/L) group were 0.64±0.04 and 1.03±0.13 respectively, and there was a significant difference (t=2.94, P<0.05). Conclusions: Low dose PFOA (50 µmol/L) exposure promotes cell proliferation, migration and invasion in the human muscle rhabdomyosarcoma cell line through inducing the expressions of MMP2, vimentin and cell cycle related genes.

[Interference research of umbilical cord mesenchymal stem cells on the pulmonary fibrosis in silicosis rats].

Objective: To explore the effect of the umbilical cord mesenchymal stem cells(UC-MSCs) on the pulmonary fibrosis in silicosis rats. Methods: SPF male Sprague Dawley rats were randomly divided into control group, silica model group and UC-MSCs treatment group with 12 rats each group. SiO(2) intra-tracheal injection(0.5 ml of 50 mg/ml/rat) were applied to silica model group and UC-MSCs treatment groups. After that UC-MSCs treatment group received 1 ml UC-MSCs suspension (3×10(6) cells/ml) by tail vein injection on the 29th, 36th, 43th and 50th day after exposure to the first silica suspension. On the 60th and 75th day after exposure to silica suspension, all animals were examed for pulmonary CT. Then the rats were euthanized on 75th day after the first exposure to silica.Lung's histopathological examination of the rats from all the groups were carried out. The content of hydroxyproline in lungs, TGF-ß1 and IL-6 in serum were examined. Results: The lung's histopathological examination showed no obvious inflammatory cell and no fibrosis in the lung tissue of the control group, there were a lot of inflammatory cell aggregation and collagen fiber deposition in silica model group, while in the UC-MSCs intervention group and treatment group, there were less inflammatory cells and collagen fiber. The rats from silica model groups had higher HYP, TGF-ß1 and IL-6 than the rats from UC-MSCs treatment group and control group. Lung fields of rats in the control group were clear and no obvious high-density shadow. Different-sized granular high-density shadows or reticular fibrous shadows were found diffusely distributed in the lungs of the rats in silica model group. Lung field of rats in UC-MSCs intervention group and treatment group were less high density shadows, and more clear. Conclusion: UC-MSCs can alleviate the pulmonary fibrosis in silica model rats through regulating the secretion of some fibrosis related cytokines.

TSGA10 is a novel candidate gene associated with acephalic spermatozoa.

Acephalic spermatozoa is a rare teratozoospermia associated with male infertility. However, the pathogenesis of this disorder remains unclear. Here, we report a 27 years old infertile male from a consanguineous family, who presented with 99% headless sperm in his ejaculate. Electron microscopic and immunofluorescence analysis suggested breakage at the midpiece of the patient's sperm cells. Subsequent whole-exome sequencing analysis identified a homozygous deletion within TSGA10 (c.211delG; p.A71Hfs*12), which resulted in the production of truncated TSGA10 protein. TSGA10 is a testis-specific protein that localized to the midpiece in the spermatozoa of a normal control; however, immunostaining failed to detect TSGA10 protein in the patient's sperm. Western blot analysis also showed complete absence of TSGA10 protein in the patient. One cycle of in vitro fertilization-assisted reproduction was conducted, but pregnancy was not achieved after embryo transfer, possibly due to poor embryo quality. Therefore, we speculate that the presence of rare sequence variants within TSGA10 may be associated with acephalic spermatozoa in humans.

A familial study of twins with severe asthenozoospermia identified a homozygous SPAG17 mutation by whole-exome sequencing.

Asthenozoospermia (AZS) is a common cause of male infertility, characterized by abnormal reduction in the motility of ejaculated spermatozoa. Here, in a patient from a consanguineous family, we identified a homozygous mutation (c.G4343A, p.R1448Q) in SPAG17 by whole-exome sequencing. The encoded protein, SPAG17, localizes to the axonemal central apparatus and is considered essential for flagellar waveform. In silico analysis revealed that R1448Q is a potential pathogenic mutation. Immunostaining and western blot assays showed that the R1448Q mutation may exert a negative effect on the steady-state of the SPAG17 protein. Therefore, SPAG17 may be a new pathogenic gene causing AZS.

DNAH6 is a novel candidate gene associated with sperm head anomaly.

Globozoospermia and acephalic spermatozoa are two rare sperm head anomalies associated with male infertility. Combination of the two phenotypes in the same patient is extremely rare, so the underlying pathogenesis of this disorder remains unclear. Here, we report a 35-year-old infertile male, who presented with 30% of sperm-lacked heads and 69% of sperm round-headed or small-headed with neck thickening in his ejaculate. Subsequent whole-exome sequencing (WES) analysis identified compound heterozygous variants within the DNAH6 gene. DNAH6 is a testis-specific-expressed protein that was localised to the neck region in the spermatozoa of normal control; however, immunofluorescent staining failed to detect DNAH6 protein in the patient's spermatozoa. Quantitative real-time PCR analysis also showed the complete absence of DNAH6 mRNA in the patient's spermatozoa. Moreover, two cycles of in vitro fertilisation (IVF)-assisted reproduction were carried out, but pregnancy was not achieved after embryo transfer. Therefore, rare sequence variants in DNAH6 might be susceptibility risks for human sperm head anomaly.

[Clinical features of adult patients with chronic active Epstein-Barr virus infection].

Objective: To investigate the clinical features of adult-onset chronic active Epstein-Barr virus infection (CAEBV). Methods: A total of 21 adult patients with CAEBV who were admitted to the department of General Internal Medicine at Peking Union Medical College Hospital from January 2006 to January 2016 were retrospectively analyzed. Demographic data, disease duration, clinical manifestations, laboratory findings, treatments and prognosis were reviewed. Results: Eighteen females and 3 males were enrolled with a mean age of 39 years. The most common clinical manifestations included fever in 20 patients, splenomegaly in 20 patients, lymphadenopathy in 18 patients, and hepatomegaly in 10 patients, followed by laryngopharyngeal disorders in 6 patients, pleural effusion and peritoneal effusion each in 5 patients, rash in 4 patients, interstitial lung disease in 3 patients, gastrointestinal hemorrhage in 2 patients, and peripheral neuropathy and pulmonary hypertension each in 1 patient. Six patients were complicated with hemophagocytic lymphohis-tioncytosis(HLH) that developed 5-17 (mean: 9) months following CAEBV onset, all of whom experienced hyperpyrexia, pancytopenia, lymphadenopathy, splenomegaly, and liver dysfunction, 3 with hepatomegaly. Nineteen of the 21 patients had received steroid therapy including 10 combined with immunosuppressive agents, 11 with antiviral therapy, and 8 with intravenous immunoglobulin. Thirteen patients died, including 10 of multiple organ failure, (including 6 of HLH) 2 of severe pulmonary infection, and 1 of lymphoma. Six patients remained on follow-up, yet 2 were missing. Conclusions: CAEBV is expected with severe condition and poor prognosis, which is likely to be complicated with HLH. Clinical physicians should pay attention to adult patients with fever, hepatosplenomegaly and lymphadenopathy, which suggests possible CAEBV.

Headless spermatozoa in infertile men.

Spermatozoa morphology, an important parameter in a semen specimen's potential fertility evaluation, is a significant factor for in vitro fertilisation in assisted reproductive technology. Eleven sterile men with headless spermatozoa, a type of human teratozoospermia, are presented. Their ejaculates' headless spermatozoa percentages were high with rare normal spermatozoa forms. Additionally, abnormal morphology (e.g. round-headed or microcephalic spermatozoa) was also found. Spermatozoa motility was somewhat affected, potentially because of the missing mitochondrial sheath at the sperm tail base. Patients who underwent assisted reproductive technology treatment experienced adverse pregnancy outcomes. Work types and corresponding environments seemed irrelevant, but specific family history may have prompted its genetic origin. Computer-assisted semen analysis systems easily mistake headless spermatozoa as oligozoospermia because of nonrecognition of the loose head. However, morphological testing, especially with an electronic microscope, clearly identifies abnormal spermatozoa. Future exploration requires more methods investigating the frequency and percentage of this morphological abnormality in different populations with varied fertility levels. Such research would estimate the probable correlation of the abnormality with other semen parameters and examine the potential developmental or genetic origins. During clinical work, medical staff should detect these cases, avoid misdiagnosis and provide proper consultation about diagnosis and assisted reproductive technology treatment.

[CT features of abnormally whole-course wide eustachian tubes with microtia and atresia].

Objective: To study the clinical and CT features of the abnormal whole-course wide of eustachian tube (AWWET) with microtia and atresia(MA). Methods: The clinical and CT data of 19 patients (20 ears) from January 2017 to December 2021 with AWWET with MA were retrospectively analyzed, including 15 males and 4 females. The age ranged from 5 to 16 years, with an average of 9.5 years. 50 patients with common MA without wide eustachian tube(ET) as a case control group, including 32 males and 18 females.The age ranged from 5 to 16 years, with an average of 9.2 years. 20 patients (40 ears) who had normal ear CT for tinnitus, otalgia as a normal control group, including 12 males and 8 females. The age ranged from 5 to 16 years, with an average of 12.5 years. We measured the dimension and length of the bony portion of the ET, the total length, the angle between the bony portion and the cartilage portion, and the horizontal angle of ET on CT imagings, and compared with 40 normal ears by SPSS 27.0 software. Results: According to the relationship between AWWET and tympanum, patients were divided into the communicated group and the blocked group. A male predominance, left ear predominance, with high incidence of hemifacial microsomia exhibited in both groups. AWWET was presented as a widened lumen on CT. In 11 ears (4 ears in the communicated group, 7 ears in the blocked group), ETs bifurcated, the upper bony tube extended to the sphenoid body, the lower part continued down to cartilaginous ET and opened onto the nasopharynx, with"mastoid-like"pneumatization of the sphenoid body in 6 ears. The middle ear deformity in case group was more serious than MA control group, especially the blocked group. The incidence of otitis media in the communicated group was lower than that in the MA control group, and 4 cases in the blocked group had effusion in the ET. Compaired with normal ear, the bony ET elongated significantly in the AWWET groups, and the whole course of ET was significantly shortened, specially in the blocked group. The angle between the bony ET and the cartilaginous ET was decreased and the horizontal angle of the ET increased in the AWWET groups, the difference was considered to indicate statistical significance(P<0.05). Conclusions: AWWET with MA is rare, a male predominance, left ear predominance, and with high incidence of hemifacial microsomia. The middle ear deformity is more serious than common MA, especially in the blocked group. The incidence of otitis media in the communicated group is significantly lower than that in the common MA, and the blocked group may be accompanied by ET inflammation.