Prediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications.

The epitranscriptome embodies many new and largely unexplored functions of RNA. A significant roadblock hindering progress in epitranscriptomics is the identification of more than one modification in individual transcript molecules. We address this with CHEUI (CH3 (methylation) Estimation Using Ionic current). CHEUI predicts N6-methyladenosine (m6A) and 5-methylcytosine (m5C) in individual molecules from the same sample, the stoichiometry at transcript reference sites, and differential methylation between any two conditions. CHEUI processes observed and expected nanopore direct RNA sequencing signals to achieve high single-molecule, transcript-site, and stoichiometry accuracies in multiple tests using synthetic RNA standards and cell line data. CHEUI's capability to identify two modification types in the same sample reveals a co-occurrence of m6A and m5C in individual mRNAs in cell line and tissue transcriptomes. CHEUI provides new avenues to discover and study the function of the epitranscriptome.

Independent and combined effects of smoking, drinking and depression on periodontal disease.

BACKGROUND: Periodontitis is a complex chronic inflammatory disease that is particularly associated with health-related conditions such as smoking, excessive drinking and depression. This research aimed to investigate the interaction between these lifestyles factors on periodontitis risk. METHODS: This study included participants who participated in the National Health and Nutrition Examination Survey in the United States between 2009 and 2014. They had completed oral health-periodontal examination, Smoking-Cigarette Use Questionnaire, Alcohol Use Questionnaire, and Patient Health Questionnaire. Periodontal clinical attachment loss (CAL) of 3 mm or more and Patient Health Questionnaire-9 (PHQ-9) of 10 scores or more were used to identify periodontitis and depression, respectively. Daily alcohol consumption in the past year was classified into three levels: low (1 drink or less), moderate (between 1 and 3 drinks), and heavy drinking (4 drinks or more), while smoking was defined as having smoked at least 100 cigarettes in one's lifetime. Then, the logistic regression combined with interaction models were used to analyze the independent and combined effects of smoking, drinking and depression on periodontitis risk. RESULTS: The results indicated a statistically significant multiplicative interaction between smoking and depression in relation to the development of periodontitis, both in the overall population (P = 0.03) and among male participants (P = 0.03). Furthermore, among individuals experiencing depression, smoking was found to significantly increase the prevalence of periodontitis by 129% in the younger age group compared to non-smokers (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.10 to 4.76). However, the interaction between smoking and alcohol consumption was only significant among females (P < 0.05). There was a dose-dependent relationship between drinking frequency and smoking on periodontitis prevalence. In the smoking population, occasional drinking (OR: 1.70; 95% CI: 1.22 to 2.37) and regular drinking (OR: 2.28; 95% CI: 1.68 to 3.11) significantly increased the prevalence of periodontitis compared to individuals without these two factors. CONCLUSION: These results suggested that there were interactive effects between smoking, drinking and depression on periodontitis risk and policies aimed at healthy behaviours and mental health may be beneficial for our oral health.

[Opportunities and challenges in accurate early diagnosis and treatment of lung cancer/pulmonary nodules].

Lung cancer remains the most prevalent and lethal malignancy in our country. Early diagnosis and treatment are crucial for improving patient prognosis in lung cancer/pulmonary nodules. Recent advancements in non-invasive/minimally invasive liquid biopsy, multi-omics, and artificial intelligence technologies have significantly enhanced the accuracy of early lung cancer/pulmonary nodule diagnosis. However, an early diagnostic method with both high sensitivity and specificity is yet to be established. Furthermore, addressing the methods and extent of early precision surgery, local precision therapy, perioperative combined treatment, and postoperative recurrence and metastasis monitoring are urgent challenges in the early management of lung cancer/pulmonary nodules. Integrating the advantages of various treatment strategies and formulating personalized and precise treatment plans is key to further improving patient survival. In the future, while exploring new therapeutic strategies, it is necessary to continuously search for biomarkers to identify the population that will benefit from the treatment effectively. Additionally, large-sample randomized controlled clinical studies should be conducted to investigate the benefits of long-term patient survival under a diverse range of treatment strategies.

[Impact of changes in malignant tumor death spectrum on life expectancy in Tianjin residents from 1999-2019].

Objective: To analyze the effects of changes in the spectrum of deaths from malignant tumors on the life expectancies of residents of different ages, sexes, and regions (urban or rural) in Tianjin from 1999 to 2019. Methods: The Abridged Life Table method and the Arriaga's decomposition method were used to calculate the effects of changes in spectrum of deaths from malignant tumors on the life expectancies of Tianjin residents of different ages, sexes, and regions. Results: During 1999-2019, the life expectancies increased by 4.96 years and 5.69 years for males and females, respectively, in Tianjin. The decreases in the mortalities from malignant neoplasms contributed 0.12 year (3.30%) and 0.03 year (0.77%) for males and females, respectively, to the increase during 1999-2007, and 0.05 year (3.13%) and 0.12 year (6.08%) for males and females, respectively, during 2007-2019. The decreases in the mortality rates of malignant tumors contributed the most to the increase among residents in the 60-69 years group, and the decreases in mortality rates of lung, gastric, esophageal, and liver cancers had relatively larger contribution. Lung cancer had a negative effect on the life expectancies of men and rural residents, but a positive effect on those of women and urban residents. The significant increases in the mortality rates of lung, colorectal, and pancreatic cancers in the ≥85 years group had a large negative effect on the overall life expectancy. Breast and ovarian cancers contributed negatively to the life expectancy of female residents. Conclusion: The overall increase in the life expectancy in Tianjin from 1999 to 2019 was mainly attributed to the elderly and the decreases in the mortality rates of gastric, esophageal, and liver cancers, among other malignancies, while the increases in the mortality rates of lung, colorectal, gallbladder, pancreatic, and breast cancers were the most significant factors hindering the increase of the life expectancy in Tianjin.

[Etiological characterization of invasive non-typhoid Salmonella strains in Guangdong Province from 2018 to 2022].

Objective: To understand the serotype distribution, drug resistance and molecular characterization of invasive non-typhoid Salmonella (iNTS) in Guangdong Province from 2018 to 2022 and provide scientific evidence for the prevention and treatment of blood flow infection caused by Salmonella. Methods: Serological identification, antimicrobial susceptibility testing, multilocus sequence typing (MLST), and whole genome sequencing were performed on Salmonella isolated from blood and stool samples in Guangdong from 2018 to 2022. Simultaneously, annotated the sequencing results for drug resistance genes and virulence factors by a microbial gene annotation system. Results: The 136 iNTS strains were divided into 25 serotypes, and Salmonella enteritidis accounted for 38.24% (52/136). The OR of other iNTS serotypes were calculated with Salmonella typhimurium as the control. The OR values of Oreninburg, Rysson, and Pomona serotypes were the highest, which were 423.50, 352.92, and 211.75, respectively. The drug resistance rate of iNTS was 0.74%-66.91%, which was lower than that of non-iNTS (3.90%-77.21%). The main iNTS of drug resistance were ampicillin and tetracycline, with resistance rates of 66.91% (91/136) and 50.00% (68/136), respectively, while the resistance rates to ciprofloxacin (5.88%,8/136), ceftazidime (5.88%,8/136), gentamicin (5.13%,7/136) and cefoxitin (0.74%, 1/136) were relatively low. iNTS carried a variety of drug-resistance genes and virulence factors, but no standard virulence factor distribution has been found. MLST cluster analysis showed that iNTS was divided into 26 sequence types, and ST11 accounted for 38.24% (52/136). Conclusions: The iNTS strains in Guangdong were dominated by Salmonella enteritidis, of which three serotypes, Oreninburg, Rison, and Pomona, may be associated with a higher risk of invasive infection during 2018 to 2022. iNTS was sensitive to clinical first-line therapeutic drugs (cephalosporins and fluoroquinolones), with highly diverse sequences and clear phylogenetic branches. ST11 was the local dominant clone group.

[Survey on the awareness rate of mpox knowledge and related factors among men who have sex with men in China].

Objective: To understand the awareness rate of mpox knowledge and related factors among men who have sex with men (MSM) in China. Methods: The survey was conducted among men aged ≥18 years who had sex with men in the past year, using the convenience sampling method. The estimated sample size was 4 312. With the assistance of social organizations of MSM in 30 provinces in China, an online questionnaire survey was conducted using anonymous self-designed questionnaires powered by www.wjx.cn during 10-14 August 2023 to collect information on socio-demographic characteristics, awareness of mpox knowledge, travel history, and sexual behaviors of the respondents. The software SAS 9.4 was used for statistical analysis. Results: There were 7 725 respondents, and the age of the respondents was (31.6±9.0) years. The results revealed that the awareness rate of mpox knowledge was 50.1% (3 872/7 725). The main routes to acquire mpox knowledge were mainly new media, including WeChat, Weibo, TikTok, and Blued social software (88.4%,6 827/7 725), while official media report was the most trusted way to acquire related knowledge (79.3%,6 129/7 725). Multivariate logistic regression analysis revealed that the factors indicated a higher awareness rate of mpox knowledge, including living in the western region or the eastern region, people were over 26 years old in early adulthood and midlife, college-educated or with higher degrees, living in towns or urban periphery, being in homosexual or in bisexual relationships, 1-5 homosexual times/months in the past 3 months, knowing their HIV infection status, paying attention to mpox knowledge very often, occasionally or rarely, and convenient ways to acquire mpox knowledge from new media and social organizations. Conclusions: The awareness rate of mpox knowledge was low among MSM in China. Efforts should be made to improve the awareness rate of mpox knowledge among those who are young, less educated, or sexually active, with targeted health education via new media and social organizations.

[Clinical characteristics of children with severe SARS-CoV-2 infection in Yunnan].

Objective: To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality. Methods: This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results: The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups (P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×109/L, 479 (298, 594) vs. 268 (124, 424) µg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) µg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases (OR=0.01, 95%CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) (OR=3.31, 95%CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) (OR=1.56, 95%CI 1.05-2.32, P=0.029) and D dimer (OR=1.49, 95%CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95%CI 0.79-0.94), 0.89 (95%CI 0.84-0.95) and 0.87 (95%CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions: Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.

[High-quality acceleration of the Chinese national schistosomiasis elimination programme to advance the building of Healthy China].

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

[Interpretation of the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030)].

On June 16, 2023, National Disease Control and Prevention Administration of the People's Republic of China, in collaboration with other ministries, formulated and issued the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030). The implementation of this plan provides an important basis for achieving the targets set in the "Healthy China 2030" action plan and the implementation of the rural revitalization strategy. This paper describes the background, principles, targets, control strategies, safeguard measures and effectiveness evaluation of the plan, in order to guide the scientific and standardized implementation of actions for schistosomiasis elimination at the grassroots level, and facilitate the progress towards elimination of schistosomiasis in China with a high quality.

[Capacity building in schistosomiasis control institutions in China: a cross-sectional study].

OBJECTIVE: To understand the current status of capacity building in schistosomiasis control institutes in schistosomiasis-endemic provinces (municipality, autonomous region) of China. METHODS: The responsibilities and construction requirements of various schistosomiasis control institutions were surveyed by expert discussions, and field interviews and visits during the period between May and June, 2023, and the questionnaire for capacity maintenance and consolidation in schistosomiasis control institutions was designed. An online questionnaire survey was conducted in county-, municipal-, and provincial-level institutions that undertook schistosomiasis control and surveillance activities through the Wenjuanxing program. The distribution of schistosomiasis control institutions, the status of institutions, departments and staff undertaking schistosomiasis control activities and the translation of scientific researches on schistosomiasis control in China were analyzed. The laboratories accredited by China National Accreditation Service for Conformity Assessment (CNAS) were considered to be capable for testing associated with schistosomiasis control, and the testing capability of schistosomiasis control institutions was analyzed. RESULTS: A total of 486 valid questionnaires were recovered from 486 schistosomiasis control institutions in 12 endemic provinces (municipality, autonomous region) of China, including 12 provincial-level institutions (2.5%), 77 municipal-level institutions (15.8%) and 397 county-level institutions (81.7%). Of all schistosomiasis control institutions, 376 (77.4%) were centers for disease control and prevention or public health centers, 102 (21.0%) were institutions for schistosomiasis, endemic disease and parasitic disease control, and 8 (1.6%) were hospitals, healthcare centers or others. There were 37 713 active employees in the 486 schistosomiasis control institutions, including 5 675 employees related to schistosomiasis control, and the proportions of employees associated with schistosomiasis control among all active employees were 5.9% (231/3 897), 5.5% (566/10 134), and 20.6% (4 878/23 682) in provincial-, municipal-, and county-level institutions, respectively. There were 3 826 full-time employees working in schistosomiasis control activities, with 30.5% (1 166/3 826), 34.6% (1 324) and 34.9% (1 336/3 826) at ages of 40 years and below, 41 to 50 years and over 50 years, and there were 1 571 (41.0%) full-time schistosomiasis control employees with duration of schistosomiasis control activities for over 25 years, and 1 358 (35.5%) employees with junior professional titles and 1 290 with intermediate professional titles (35.5%), while 712 (18.6%) full-time employees working in schistosomiasis control activities had no professional titles. The three core schistosomiasis control activities included snail control (26.3%, 374/1 420), epidemics surveillance and management (25.4%, 361/1 420) and health education (18.8%, 267/1 420) in schistosomiasis control institutions. The Kato-Katz method, miracidium hatching test with nylon gauzes, and indirect haemagglutination assay (IHA) were the most commonly used techniques for detection of schistosomiasis, and there were less than 50% laboratories that had capabilities or experimental conditions for performing enzyme-linked immunosorbent assay (ELISA), dipstick dye immunoassay (DDIA), dot immunogold filtration assay (DIG-FA), loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) assays. During the period from 2018 to 2022, schistosomiasis control institutions had undertaken a total of 211 research projects for schistosomiasis control, with a total funding of 18.596 million RMB, published 619 articles, participated in formulation of 13 schistosomiasis control-related criteria, and applied for 113 schistosomiasis control-related patents, including 101 that were granted, and commercialized 4 scientific research outcomes. CONCLUSIONS: The proportion of independent specialized schistosomiasis control institutions is low in schistosomiasis control institutions in China, which suffers from problems of unsatisfactory laboratory testing capabilities, aging of staff and a high proportion of low-level professional titles. More investment into and intensified schistosomiasis control activities and improved capability building and talent cultivation in schistosomiasis control institutions are recommended to provide a powerful support for high-quality elimination of schistosomiasis in China.

[Magnetic resonance imaging T2 mapping could reflect disease status in patients with dermatomyositis or polymyositis].

This study aimed to explore the value of magnetic resonance imaging (MRI) T2 mapping in the assessment of dermatomyositis (DM) and polymyositis (PM). Thirty-three confirmed cases (myosin group) and eight healthy volunteers (healthy control group) at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Kunming Medical University, from October 2016 to December 2017, were collected and analyzed. Multiple parameters of the myosin group were quantified, including creatine kinase (CK), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3, and complement C4. Disease status was evaluated using a panel of tools: myositis disease activity assessment tool-muscle (MDAAT-muscle), myositis disease activity assessment tool-whole (MDAAT-all), health assessment questionnaire (HAQ), medical outcomes study health survey short form-36 item (SF-36), hand muscle strength test (MMT-8) score, and MRI T2 mapping of muscle (22 muscles in the pelvis and thighs) T2 values. The results showed that in the myositis group, the measurements for CK, ESR, CRP, complement C3, and complement C4 were 457.2 (165.6, 1 229.2) IU/L, 20 (10, 42) mm/1h, 3.25 (2.38, 10.07) mg/L, 0.90 (0.83, 1.06) g/L, and 0.18 (0.14, 0.23) g/L, respectively. The scores for MMT-8, MDAAT-muscle, MDAAT-all, HAQ, and SF-36 were 57.12±16.23, 5.34 (4.00, 6.00), 34.63±12.62, 1.55 (0.66, 2.59), and 44.66±7.98, respectively. T2 values were significantly higher in all 22 muscles of the pelvis and thighs of patients with DM or PM compared with the healthy controls [(54.99±11.60)ms vs. (36.62±1.66)ms, P<0.001], with the most severe lesions in the satrorius, iliopsoas, piriformis, gluteus minimus, and gluteus medius muscles. The total muscle T2 value in the myositis group was positively correlated with CK, MDAAT-muscle, MDAAT-all, and HAQ (r=0.461, 0.506, 0.347, and 0.510, respectively, all P<0.05). There was a negative correlation between complement C4, SF-36, and MMT-8 scores (r=-0.424, -0.549, and -0.686, respectively, all P<0.05). Collectively, the findings from this study suggest that MRI T2 mapping can objectively reflect the disease status of DM and PM.

[Non-primary solid malignancies of breast in needle core biopsy: a clinicopathological analysis of 23 cases].

Objective: To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy. Methods: Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers. Results: All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors. Conclusions: The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

[Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma. Methods: Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children's Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics. Results: Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease. Conclusions: Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

Family matters inside the order Agaricales: systematic reorganization and classification of incertae sedis clitocyboid, pleurotoid and tricholomatoid taxa based on an updated 6-gene phylogeny.

The phylogenetic position of several clitocyboid/pleurotoid/tricholomatoid genera previously considered incertae sedis is here resolved using an updated 6-gene dataset of Agaricales including newly sequenced lineages and more complete data from those already analyzed before. Results allowed to infer new phylogenetic relationships, and propose taxonomic novelties to accommodate them, including up to ten new families and a new suborder. Giacomia (for which a new species from China is here described) forms a monophyletic clade with Melanoleuca (Melanoleucaceae) nested inside suborder Pluteineae, together with the families Pluteaceae, Amanitaceae (including Leucocortinarius), Limnoperdaceae and Volvariellaceae. The recently described family Asproinocybaceae is shown to be a later synonym of Lyophyllaceae (which includes also Omphaliaster and Trichocybe) within suborder Tricholomatineae. The families Biannulariaceae, Callistosporiaceae, Clitocybaceae, Fayodiaceae, Macrocystidiaceae (which includes Pseudoclitopilus), Entolomataceae, Pseudoclitocybaceae (which includes Aspropaxillus), Omphalinaceae (Infundibulicybe and Omphalina) and the new families Paralepistaceae and Pseudoomphalinaceae belong also to Tricholomatineae. The delimitation of the suborder Pleurotineae (= Schizophyllineae) is discussed and revised, accepting five distinct families within it, viz. Pleurotaceae, Cyphellopsidaceae, Fistulinaceae, Resupinataceae and Schizophyllaceae. The recently proposed suborder Phyllotopsidineae (= Sarcomyxineae) is found to encompass the families Aphroditeolaceae, Pterulaceae, Phyllotopsidaceae, Radulomycetaceae, Sarcomyxaceae (which includes Tectella), and Stephanosporaceae, all of them unrelated to Pleurotaceae (suborder Pleurotineae) or Typhulaceae (suborder Typhulineae). The new family Xeromphalinaceae, encompassing the genera Xeromphalina and Heimiomyces, is proposed within Marasmiineae. The suborder Hygrophorineae is here reorganized into the families Hygrophoraceae, Cantharellulaceae, Cuphophyllaceae, Hygrocybaceae and Lichenomphaliaceae, to homogenize the taxonomic rank of the main clades inside all suborders of Agaricales. Finally, the genus Hygrophorocybe is shown to represent a distinct clade inside Cuphophyllaceae, and the new combination H. carolinensis is proposed. Taxonomic novelties: New suborder: Typhulineae Vizzini, Consiglio & P. Alvarado. New families: Aphroditeolaceae Vizzini, Consiglio & P. Alvarado, Melanoleucaceae Locq. ex Vizzini, Consiglio & P. Alvarado, Paralepistaceae Vizzini, Consiglio & P. Alvarado, Pseudoomphalinaceae Vizzini, Consiglio & P. Alvarado, Volvariellaceae Vizzini, Consiglio & P. Alvarado, Xeromphalinaceae Vizzini, Consiglio & P. Alvarado. New species: Giacomia sinensis J.Z. Xu. Stat. nov.: Cantharellulaceae (Lodge, Redhead, Norvell & Desjardin) Vizzini, Consiglio & P. Alvarado, Cuphophyllaceae (Z.M. He & Zhu L. Yang) Vizzini, Consiglio & P. Alvarado, Hygrocybaceae (Padamsee & Lodge) Vizzini, Consiglio & P. Alvarado, Lichenomphaliaceae (Lücking & Redhead) Vizzini, Consiglio & P. Alvarado. New combination: Hygrophorocybe carolinensis (H.E. Bigelow & Hesler) Vizzini, Consiglio & P. Alvarado. New synonyms: Sarcomyxineae Zhu L. Yang & G.S. Wang, Schizophyllineae Aime, Dentinger & Gaya, Asproinocybaceae T. Bau & G.F. Mou. Incertae sedis taxa placed at family level: Aphroditeola Redhead & Manfr. Binder, Giacomia Vizzini & Contu, Hygrophorocybe Vizzini & Contu, Leucocortinarius (J.E. Lange) Singer, Omphaliaster Lamoure, Pseudoclitopilus Vizzini & Contu, Resupinatus Nees ex Gray, Tectella Earle, Trichocybe Vizzini. New delimitations of taxa: Hygrophorineae Aime, Dentinger & Gaya, Phyllotopsidineae Zhu L. Yang & G.S. Wang, Pleurotineae Aime, Dentinger & Gaya, Pluteineae Aime, Dentinger & Gaya, Tricholomatineae Aime, Dentinger & Gaya. Resurrected taxa: Fayodiaceae Jülich, Resupinataceae Jülich. Citation: Vizzini A, Alvarado P, Consiglio G, Marchetti M, Xu J (2024). Family matters inside the order Agaricales: systematic reorganization and classification of incertae sedis clitocyboid, pleurotoid and tricholomatoid taxa based on an updated 6-gene phylogeny. Studies in Mycology 107: 67-148. doi: 10.3114/sim.2024.107.02.

Quantification of left atrial strain in patients with idiopathic inflammatory myopathy using cardiovascular magnetic resonance feature tracking.

BACKGROUND: Left atrial (LA) dysfunction is involved in idiopathic inflammatory myopathy (IIM). Multiparametric cardiovascular magnetic resonance (CMR) strain imaging is a feasible and reproducible tool for examining global and regional LA functions, as well as left ventricular (LV) function in IIM patients. AIM: The aim of this study was to evaluate the feasibility and reproducibility of LA strain occurrence and strain rate for LA function assessment using CMR in IIM cases. MATERIALS AND METHODS: A total of 36 IIM and 42 healthy control cases were included. Baseline ventricular function was comparatively assessed in both groups. LA strain occurrence and strain rate were examined by cine cardiac magnetic resonance imaging [MRI] utilizing an in-house semiautomated technique. LA global function indexes were quantitated, including reservoir, conduit, and booster-pump functions. RESULTS: A total of 78 participants were enrolled in this study. There was no significant difference in left/right ventricular routine functions between IIM patients and control individuals (p>0.05); the same results (p>0.05) was also observed between patients with high hs-cTnI and normal. However, LV mass index had significant difference (p1=0.003, p2<0.01). Compared with IIM patients and control individuals, only total strain (εs) (p4=0.046) and passive strain (εe) (p4=0.002) showed significant difference, and in cases with high hs-cTnI and normal hs-cTnI, there are differences for εs (p3=0.012) and εe (p4=0.047). The strongest association was found between εe and LV ejection fraction (LVEF) (r=0.581, p<0.01). CONCLUSION: IIM cases have altered LA reservoir and conduit functions, and LA strain could reflect LA function.

[Application of optical coherence tomography in the evaluation of cervical lesions: a multicenter study].

Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.

[Rho kinase inhibitor Y27632 promotes survival of human induced pluripotent stem cells during differentiation into functional midbrain dopaminergic progenitor cells in vitro].

OBJECTIVE: To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells (hiPSCs-NECs) into functional midbrain dopaminergic progenitor cells (DAPs). METHODS: HiPSCs were cultured in mTeSRTM medium containing DMH1 (10 µmol/L), SB431542 (10 µmol/L), SHH (200 ng/mL), FGF8 (100 ng/mL), purmorphamine (2 µmol/L), CHIR99021 (3 µmol/L), and N2 (1%) for 12 days to induce their differentiation into primitive neuroepithelial cells (NECs). The hiPSCs-NECs were digested with collagenase Ⅳ and then cultured in neurobasal medium supplemented with 1% N2, 2% B27-A, BDNF (10 ng/mL), GDNF (10 ng/mL), AA, TGF-ß, cAMP, and 1% GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632, and the culture medium was changed the next day to remove Y27632. Continuous induction was performed until day 28 to obtain DAPs. RESULTS: Human iPSCs expressed the pluripotency markers OCT4, SOX2, Nanog, and SSEA1 and were positive for alkaline phosphatase staining. The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2, nestin, and PAX6. In digested hiPSCs-NECs, the addition of 5 µmol/L Y27632 significantly promoted survival of the adherent cells, increased cell viability and the proportion of S-phase cells (P < 0.01), and reduced the rate of apoptotic cells (P < 0.05). On day 28 of induction, the obtained cells highly expressed the specific markers of DAPS (TH, FOXA2, NURR1, and Tuj1). CONCLUSION: Treatment with Y27632 (5 µmol/L) for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation, which indirectly enhances the efficiency of cell differentiation.

Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications.

Introduction: The impact of female biological sex on the development of heart failure with preserved ejection fraction (HFpEF) and its associated kidney disease and vascular endothelial dysfunction is still controversial. Whether females are protected from HFpEF and associated complications is not well established. Previous studies report conflicting prevalence between genders. We hypothesize that female mice are unprotected from HFpEF and its associated kidney disease and vascular endothelial dysfunction. Methods: Eight-week-old female mice were divided into four groups: control groups receiving a standard diet and water for either 5 or 16 weeks, and HFpEF groups fed a high-fat diet (HFD, Rodent Diet With 60 kcal% Fat) and N [w]-nitro-l-arginine methyl ester (L-NAME - 0.5 g/L) in the drinking water for 5 or 16 weeks. Various measurements and assessments were performed, including echocardiography, metabolic and hypertensive evaluations, markers of heart and kidney injury, and assessment of vascular endothelial function. Results: Female mice with HFD and L-NAME developed HFpEF at 5 weeks, evidenced by increased E/E' ratio, reduced cardiac index, left ventricular mass, and unchanged ejection fraction. After 16 weeks, HFpEF worsened. Metabolic disorders, hypertension, lung wet/kidney weight increase, exercise intolerance, and cardiac/renal injury markers were observed. Vascular endothelial dysfunction was associated with ER stress and fibrosis induction. Conclusions: We found that female mice are susceptible to the development of HFpEF and its associated kidney disease and vascular endothelial dysfunction. Our data support the concept that the female sex does not protect from HFpEF and its associated kidney disease and vascular endothelial dysfunction when disease risk factors are present.