[Concomitant extragenital malformations of female reproductive tract anomalies: analysis of 444 cases in Peking Union Medical College Hospital].

Objective: To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies. Methods: A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed. Results: A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common. Conclusions: Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

Biocontrol of strawberry Botrytis gray mold and prolong the fruit shelf-life by fumigant Trichoderma spp.

Objectives To screen high active volatile organic compounds (VOCs)-producing Trichoderma isolates against strawberry gray mold caused by Botrytis cinerea, and to explore their antagonistic mode of action against the pathogen. VOCs produced by nine Trichoderma isolates (Trichoderma atroviride T1 and T3; Trichoderma harzianum T2, T4 and T5; T6, T7, T8 and T9 identified as Trichoderma asperellum in this work) significantly inhibited the mycelial growth (13.9-63.0% reduction) and conidial germination (17.6-96.3% reduction) of B. cinerea, the highest inhibition percentage belonged to VOCs of T7; in a closed space, VOCs of T7 shared 76.9% and 100% biocontrol efficacy against gray mold on strawberry fruits and detached leaves, respectively, prolonged the fruit shelf-life by 3 days in presence of B. cinerea, completely protected the leaves from B. cinerea infecting; volatile metabolites of T7 damaged the cell membrane permeability and integrity of B. cinerea, thereby inhibiting the mycelial growth and conidial germination. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the VOCs contain 23 potential compounds, and the majority of these compounds were categorised as alkenes, alcohols, and esters, including PEA and 6PP, which have been reported as substances produced by Trichoderma spp. T. asperellum T7 showed high biofumigant activity against mycelial growth especially conidial germination of B. cinerea and thus protected strawberry fruits and leaves from gray mold, which acted by damaging the pathogen's plasma membrane and resulting in cytoplasm leakage, was a potential biofumigant for controlling pre- and post-harvest strawberry gray mold.

[The prediction value of combined serum levels of TMAO and TML for poor prognosis in patients with heart failure].

Objective: To evaluate the predictive value of combined serum levels of trimethylamine N-oxide (TMAO) and trimethyllysine (TML) for poor prognosis in patients with heart failure. Methods: This single-center prospective cohort study included hospitalized patients with heart failure and complete baseline data from the Department of Cardiology at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2017 to December 2020. Patients were categorized into four groups based on median serum levels of TMAO and TML after admission: TMAO low level TML low level group (TMAO<9.7 µmol/L, TML<0.73 µmol/L), TMAO low level TML high level group (TMAO<9.7 µmol/L, TML≥0.73 µmol/L), TMAO high level TML low level group (TMAO≥9.7 µmol/L, TML<0.73 µmol/L) and TMAO high level TML high level group (TMAO≥9.7 µmol/L, TML≥0.73 µmol/L). The primary endpoint was a composite endpoint of cardiovascular death and readmission for heart failure. Multiple factor Cox regression analysis was conducted to evaluate the correlation between serum TMAO and TML levels and poor prognosis in patients with heart failure. Results: A total of 471 patients with heart failure were included, with an mean age of (62.5±12.0) years and a median follow-up time of 1.61 (1.06, 2.90) years. Multivariate Cox regression analysis showed that after adjusting for age, gender, and traditional risk factors, the TMAO high level TML high level group had a higher incidence of primary endpoint events compared to the TMAO low level TML low level group (HR=1.71, 95%CI 1.05-2.77, P=0.03). Conclusion: Elevated serum levels of both TMAO and TML can effectively predict the occurrence of long-term adverse events in patients with heart failure.

[Application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection in the sphincter-preserving resection of low rectal cancer].

Objectives: To investigate the application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection (LDER) in the anal preservation treatment of low rectal cancer. Methods: Inclusion criteria: (1) age was 18-70; (2) the distance of the lower tumor edge from the anal verge was 4-5 cm; (3) primary tumor with a diameter ≤3 cm; (4) preoperative staging of T1~2N1~2M0; (5) "difficult pelvis", defined as ischial tuberosity diameter<10 cm or body mass index>25 kg/m2; (6) patients with strong intention for sphincter preservation; (7) no preoperative treatment (e.g., chemotherapy, radiotherapy, molecular targeted therapy, or immunotherapy); (8) no lateral lymph node enlargement; (9) no previous anorectal surgery; (10) patients with good basic condition who could tolerate surgery. Exclusion criteria: (1) previously suffered from malignant tumors of the digestive tract or currently suffering from malignant tumors out of the digestive tract; (2) patients with preoperative anal dysfunction (Wexner score ≥ 10), or fecal incontinence. The specific surgical steps are as follows: the distal end of the rectum was dissected to the level of the interspace between internal and external sphincters of anal canal. Five centimeters proximal to the tumor, the mesorectum was ligated, and a liner stapler was used to transect the rectum. The distal rectum with the tumor were then everted and extracted through the anus. The rectum was transected 0.5-1.0 cm distal to the tumor with a linear stapler. Full thickness suture was used to reinforce the stump of the rectum, which was then brought back into the pelvic cavity. Finally, an end-to-end anastomosis between the colon and the rectum was performed. A retrospective descriptive study was performed of the clinical and pathological data of 12 patients with T1-T2 stage low rectal cancer treated with LDER at Henan Provincial People's Hospital from January 2020 to December 2022. Results: All 12 patients successfully completed LDER with sphincter preservation, without conversion to open surgery or changes in surgical approach. The median surgical time was 272 (155-320) minutes, with a median bleeding volume of 100 (50-200) mL. No protective stoma was performed, and all patients received R0 resection. The average hospital stay was 9 (7-15) days. There were no postoperative anastomotic leakage or perioperative deaths. All 12 patients received postoperative follow-up, with a median follow-up of 12 months (6-36 months) and a Wexner score of 8 (5-14) at 6 months postoperatively. There was no tumor recurrence or metastasis during the follow-up period. Conclusions: LDER is safe and effective for the treatment of low rectal cancer.

[Clinical, imaging and pathological and molecular characteristics of simple bone cyst].

Objective: To investigate the radiologic, pathologic, and molecular features of simple bone cysts (SBC), and their differential diagnoses. Methods: Fourteen cases of SBC were collected at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022, and fluorescence in situ hybridization (FISH) was performed for retrospective analysis. Results: There were 14 patients, including 7 females and 7 males, with age range of 7 to 45 (median 29) years. The most common complaint was pain, including 4 cases with pathological fracture and 5 with history of previous trauma. The tumor size ranged from 3.4 to 13.5 (median 5.6) cm. The lesion involved the femur (n=4), humerus (n=5) and iliac bone (n=5). Radiologic diagnoses included SBC, aneurysmal bone cyst, and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia. Histologically, the cyst walls of the lesions were composed of fibrous tissue, fibrin-like collagen deposits, bone-like matrix and occasional woven bone. The lesional cells were spindled to ovoid, with scattered osteoclast-like giant cells, foamy histiocytes, hemosiderin deposits and cholesterol clefts. In 6 cases there were nodular fasciitis-like areas. Immunohistochemically, the spindled to ovoid cells were positive for SMA, EMA and SATB2 in varying degrees. FISH detection was performed in all 14 cases and EWSR1/FUS rearrangement were found in 9 cases. One case of FUS::NFATC2 fusion was detected by next-generation sequencing. Nine cases of SBC with the rearrangement were more cellular, and there were more mitotic figures in the recurrent FUS::NFATC2 fusion tumor. Clinical follow-up was obtained in all 14 cases with the time ranging from 5 to 105 (mean 46) months. Amongst them, the tumor with FUS::NFATC2 rearrangement had local recurrence twice after the first local excision, but had no more recurrence or metastasis 34 months after the subsequent segmental resection. The other 13 cases had no recurrence. Conclusions: EWSR1 or FUS rearrangement is most commonly identified in SBC, suggesting that SBC might be a neoplastic disease. In cases where the radiologic appearance and histomorphology are difficult to differentiate from aneurysmal bone cyst, FISH detection can aid in the definitive diagnosis.

[Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone].

Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses. Results: A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) (χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy (HR=0.11, 95%CI 0.05-0.27), achievement of efficacy of partial response or better (HR=0.47, 95%CI 0.34-0.66), and non-aggressive relapse (HR=0.25, 95%CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion: In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

[Ewing's sarcoma of central nervous system: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological characteristics, pathological diagnosis of Ewing's sarcoma of the central nervous system. Methods: Six cases of Ewing's sarcoma of the central nervous system diagnosed at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from 2015 to 2022 were collected. The clinical manifestations, histological morphology, immunophenotype and molecular genetics of these cases were analyzed. The related literature was reviewed. Results: There were four males and two females, with a male to female ratio of 2∶1. The onset age was 17-40 years, with a median age of 23 years. All 6 tumors were located in the spinal cord (2 cases of cervical vertebra, 1 case of thoracic vertebra, 2 cases of lumbar vertebra, and 1 case of sacral vertebra). The patients' clinical manifestations were mostly lumbago, weakness and numbness of lower limbs/limbs. In 1 case, the tumor recurred and metastasized to the suprasellar region and the third ventricle. Microscopically, the tumor showed diffuse infiltrative growth. In some cases, the tumor was closely related to the spinal meninges. The tumor cells were arranged in sheet, lobular, thin-rope, and nest-like patterns. Homer-Wright rosette was visible. The tumor cells were small to medium in size, and most of them had scant cytoplasm. A few cells had clear cytoplasm. Some areas were rhabdoid. The tumor cell nuclei showed focal mild pleomorphism. The chromatin was uniform and delicate while the nucleoli were not obvious. Mitosis was commonly seen. The tumor was separated by fibrous connective tissue and may be accompanied by mucinous degeneration. Immunohistochemistry showed that all tumors were positive for CD99, NKX2.2, Fli1, ERG. ATRX, H3K27me3, INI1 and BRG1 were all retained. Immunohistochemical stains for EMA, GFAP and Olig2 were negative. The Ki-67 proliferation index was 30%-70%. EWSR1 break-apart FISH test was positive. Conclusions: Ewing's sarcoma is rare in the central nervous system and needs to be distinguished from a variety of neoplasms with primitive undifferentiated small cell morphology. Immunohistochemistry and molecular genetics may be required for a proper diagnosis.

First report of leaf spot disease caused by Alternaria alternata on Polygonatum cyrtonema Hua in Hunan Province of China.

Polygonatum cyrtonema Hua, a perennial plant of the Asparagaceae family, is an important herb in Chinese medicine and is mainly grown in the Chinese provinces of Guizhou, Hunan, Yunnan, Anhui, and Zhejiang (Chen et al. 2021). In June 2021, a new case of leaf spot disease was detected in an 80 m2 plantation of P. cyrtonema on Xuefeng Mountain, Huaihua City, Hunan Province (27°17'30″N, 110°24'20″E). It infected almost 40% of the total planted area. Initially, irregular light brown spots appeared on the leaves, gradually turning dark brown and coalescing to form large necrotic areas, after which the affected plant turned yellow and eventually died. Ten disease samples were collected from ten plants in the plantation area. The leading edge of necrotic tissues were rinsed with sterile water and then disinfected with 3% hydrogen peroxide for 30 s, followed by 75% ethanol for 90 s, and rinsed three times with sterile water. Samples were then placed on water agar plates and incubated in the dark in a constant temperature incubator at 28 ℃ for 3-5 days. After mycelial growth was observed in the media, the hyphae were transferred to potato dextrose agar plates and incubated for 3-5 days at 28 ℃ in the dark. Ultimately, 12 purified fungal isolates were obtained, some of which were morphologically similar, including 10 that were Alternaria (83.3% isolation rate). Three representative isolates (HJYB1, HJYB2, and HJYB3) were selected for further study. The initial colonies were grayish green with white fluffy mycelia on the surface and a prominent white rim, which became brown with dense, cottony aerial mycelia as the colonies matured. The conidia were obpyriform or ellipsoidal, pale to dark brown, with 0-4 transverse and 0-3 longitudinal septa, some with a short cylindrical beak at the tip. They measured 11.826-28.873 × 6.231-26.018 µm (n = 100). To further confirm the identity of the isolates, their rDNA internal transcribed spacer region (ITS), ß-microtubulin (TUB2) and translation elongation factor-1 (TEF-1) genes were amplified and sequenced using the ITS4/ITS5, TUB2F/R and EF-526F/1567R primers, respectively (Hong et al. 2006). The sequences were submitted to GenBank (ITS: OR513924, OR513964, OR519874; TUB2: OR526928, OR533421, OR526929; TEF: OR526926, OR533420, OR526927). A concatenated phylogenetic tree of the three genes showed that the isolate clustered significantly with Alternaria alternata. Based on morphological identification and phylogenetic tree analysis, the isolate was identified as A. alternata. We carried out pathogenicity tests on four uniformly growing P. cyrtonema plants. Three of these plants were used as experimental plants and one as a control. For each plant, three young leaves were selected and inoculated with 6 × 6 mm PDA blocks, while sterile PDA blocks were used as controls. The treated plants were subjected to 10 days of stable temperature in a climatic chamber set at 28°C, 80% constant relative humidity and 12 hours of light per day. The pathogenic lesions appeared and the pathogens re-isolated from the diseased leaves showed similar morphological characteristics to representative isolates and were confirmed as A. alternata by DNA sequencing, thus fulfilling Koch's postulates. A. alternata is the major causal agent of leaf spot on P. sibiricum (Zou et al. 2023) and Agrimonia pilosa (Jiang et al. 2023). As far as we know, leaf necrosis caused by A. tenuissima has been found on P. cyrtonema (Li et al. 2020). To our knowledge, this is the first report of A. alternata causing leaf spot disease in P. cyrtonema. These findings form the basis for the management of this leaf spot disease.

[Primary hepatic angiosarcoma: a clinicopathological analysis of nine cases].

Objective: To investigate the clinical manifestations, histomorphology, and differential diagnosis of primary hepatic angiosarcoma. Methods: Nine cases of primary hepatic angiosarcoma diagnosed in the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2021 were collected, including biopsy and surgical specimens. The histomorphology, clinical, and radiologic findings were analyzed. The relevant literature was also reviewed. Results: There were six males and three females, aged 30 to 73 years (mean 57 years). Grossly, the growth pattern of the tumor was classified as either mass formation or non-mass formation (sinusoidal). Microscopically, the mass-forming primary hepatic angiosarcoma were further subdivided into vasoformative or non-vasoformative growth patterns; and those non-vasoformative tumors had either epithelioid, spindled, or undifferentiated sarcomatoid features. Sinusoidal primary hepatic angiosarcoma on the other hand presented with markedly dilated and congested blood vessels of varying sizes, with mild to moderately atypical endothelial cells. Follow-up in all nine cases revealed 8 mortality ranging from 1 to 18 months (mean 5 months) from initial diagnosis. One patient was alive with disease within a period of 48 months. Conclusions: Primary hepatic angiosarcoma is a rare entity with a wide spectrum of histomorphology, and often misdiagnosed. It should be considered when there are dilated and congested sinusoids, with overt nuclear atypia. The overall biological behavior is aggressive, and the prognosis is worse.

[Malignant peripheral nerve sheath tumor: a clinicopathological analysis].

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

[A clustered epidemic investigation of non-marital non-commercial heterosexual contact of HIV in Zhejiang Province].

Objective: To identify the transmission relationship between HIV infection cases the non-marital non-commercial heterosexual contact in Zhejiang Province. Methods: When HIV positive was informed during January 2020 to January 2022, the staff conducted an epidemiological investigation to collect cases information on sociodemographic characteristics, mobility information, past HIV testing history, high-risk sexual behaviors, sexual partners, and etcetera. At the same time, 6-8 ml of blood from the new diagnosis of people infected with HIV before antiviral treatment was collected to separate the bleeding plasma. pol gene was amplified by nucleic acid extraction and PCR, sequenced by Sequencer 5.0 software, and Cytoscape 3.6.0 software was used to draw HIV molecular transmission network. Results: From January 2020 to January 2022, 88 HIV infected individuals were found in Pujiang County, of which 74 were transmitted through heterosexual transmission, of which 31 were infected through non-marital non-commercial heterosexual contact. Preliminary case studies have found that three female cases have engaged in unprotected non-marital non-commercial heterosexual contact with one male case. Among the 4 infected individuals, 2 of their spouses tested positive for HIV antibodies. Molecular transmission network monitoring was carried out on 65 newly diagnosed cases of heterosexual transmission with acquired sequences, forming 9 transmission clusters. The largest cluster contained 10 cases. A total of 11 HIV-infected individuals were involved in this HIV cluster epidemic. They were 3 males and 8 females, all over 50 years old and were farmers or rural housewives. They were traced to 7 sexual partners (6 negatives of HIV, 1 undetected). Among the 18 respondents' sexual social network relationships, there were 6 couples, 8 permanent partners, and 3 temporary partners. Among 11 HIV infected individuals, there were 9 cases of non-marital non-commercial heterosexual transmission and 2 cases of intramarital transmission. The epidemiological association between 7 non-married non-commercial heterosexual partners and case 2 (56-year-old male farmer), 3 cases confirmed by epidemiological investigation and molecular transmission cluster results, 3 cases confirmed by molecular transmission cluster and epidemiological investigation results, and 1 case confirmed by epidemiological investigation results. Conclusions: The transmission mode of this cluster epidemic was to spread HIV through heterosexual sex with a male case as the core, then cause the transmission within marriage and between fixed sexual partners. The combination of epidemiological investigation and molecular transmission network traceability survey supports the conclusion of this study.

Identification of hub anoikis-associated genes and risk signature in cutaneous melanoma.

OBJECTIVE: As one of the most lethal and aggressive cutaneous malignancies, cutaneous melanoma (CM) greatly threatens human health and has long challenged clinicians because of its poor therapeutic response. Anoikis is a newly discovered form of apoptosis that was originally identified in the extracellular matrix (ECM). Recent studies have reported that anoikis is central to cancer metastasis. The aim of this study is to explore the role of anoikis-associated genes in CM. MATERIALS AND METHODS: We identified hub anoikis-associated genes in CM and constructed a risk signature for patients with CM. Gene expression from The Cancer Genome Atlas (TCGA) database was used to screen hub anoikis-associated genes connected with CM, and the Gene Expression Omnibus (GEO) dataset was applied to externally validate the identified genes. Weighted gene co-expression network analysis (WGCNA), differential expression, univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) analyses were used to identify hub genes. Immune cell infiltration in CM was also evaluated to explore the association between hub genes and immune heterogeneity. Finally, an anoikis-associated prognostic model was constructed. RESULTS: Following complex analysis, FASLG, SOD2, BST2, PIK3R2, IKZF3, CDK2, and RAC3 were identified as hub anoikis-associated genes. Indeed, Kaplan-Meier and receiver operating characteristic analyses suggested that the expression patterns of hub genes can be used as prognostic factors for CM survival. The expression and survival trends of hub genes were verified in the validation cohort. Immune cell infiltration analysis showed that the number of immune cells varied among patients with CM and identified seven genes. Furthermore, functional analyses indicated that the constructed risk signature was significantly associated with patient survival, age, and tumor growth and could also serve as an independent prognostic factor for patients with CM. CONCLUSIONS: We suggest that the hub genes FASLG, SOD2, BST2, PIK3R2, IKZF3, CDK2, and RAC3 are involved in the anoikis-associated signature. The pattern of hub anoikis-associated genes may have a prognostic potential for CM progression and overall patient survival.

Dietary isoleucine supplementation enhances growth performance, modulates the expression of genes related to amino acid transporters and protein metabolism, and gut microbiota in yellow-feathered chickens.

This study investigated the effects of dietary isoleucine (Ile) on growth performance, intestinal expression of amino acid transporters, protein metabolism-related genes and intestinal microbiota in starter phase Chinese yellow-feathered chickens. Female Xinguang yellow-feathered chickens (n = 1,080, aged 1 d) were randomly distributed to 6 treatments, each with 6 replicates of 30 birds. Chickens were fed diets with 6 levels of total Ile (6.8, 7.6, 8.4, 9.2, 10.0, and 10.8 g/kg) for 30 d. The average daily gain and feed conversion ratio were improved with dietary Ile levels (P < 0.05). Plasma uric acid content and glutamic-oxalacetic transaminase activity were linearly and quadratically decreased with increasing dietary Ile inclusion (P < 0.05). Dietary Ile level had a linear (P < 0.05) or quadratic (P < 0.05) effect on the jejunal expression of ribosomal protein S6 kinase B1 and eukaryotic translation initiation factor 4E binding protein 1. The relative expression of jejunal 20S proteasome subunit C2 and ileal muscle ring finger-containing protein 1 decreased linearly (P < 0.05) and quadratically (P < 0.05) with increasing dietary Ile levels. Dietary Ile level had a linear (P = 0.069) or quadratic (P < 0.05) effect on the gene expression of solute carrier family 15 member 1 in jejunum and solute carrier family 7 member 1 in ileum. In addition, bacterial 16S rDNA full-length sequencing showed that dietary Ile increased the cecal abundances of the Firmicutes phylum, and Blautia, Lactobacillus, and unclassified_Lachnospiraceae genera, while decreased that of Proteobacteria, Alistipes, and Shigella. Dietary Ile levels affected growth performance and modulated gut microbiota in yellow-feathered chickens. The appropriate level of dietary Ile can upregulate the expression of intestinal protein synthesis-related protein kinase genes and concomitantly inhibit the expression of proteolysis-related cathepsin genes.

Research on sports reform in the network era based on educational psychology in the context of the COVID-19.

Introduction: In the context of the continuous progress of the "Internet+" era and the exceptionally severe outbreak of the Covid-19, online education confronts many challenges and also brings unlimited development opportunities. Methods: In this paper, taking six universities with sports majors in Chongqing as the research objects, we analyze the current situation and problems of the development and construction of online education resources for sports in colleges and universities by browsing the official websites of colleges and universities, investigating the cooperation between colleges and universities and Massive Open Online Course (MOOC), and conducting a questionnaire survey on students. Results: The results show that it is necessary to innovate the traditional inefficient classroom teaching model based on the values of adapting to the characteristics of the "Internet+" era and learning advanced teaching rules, thus optimizing teaching effectiveness and fostering students' independent learning, thinking and innovation. Discussion: We investigated students' online learning habits, their experience of using online education platform and the difficulties they encountered in the process, based on which two issues were raised: learning needs and learning experience.

[CIC-rearranged sarcoma with rhabdoid features: a clinicopathological analysis].

Objective: To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of CIC-rearranged sarcoma (CRS) with rhabdoid features. Methods: The clinical and pathologic data of two cases of CRS diagnosed between 2019 and 2021 at the Department of Pathology, Jiangsu Province Hospital were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The relevant literature was reviewed. Results: Both patients were female, one was 58 years old, with tumor located in left thigh; the other was 43 years old, with tumor located in left pelvic cavity. Microscopically, both tumors were composed of small to medium-sized round, oval cells, arranged in nodules or sheets. The tumor cells showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Both cases showed rhabdoid phenotype with myxoid stromal changes. Immunohistochemically, both cases were positive for CD99 and c-myc. High WT1 reactivity was seen in classic area, with low reactivity in rhabdoid area. There was no INI1 lost in both cases. Both were negative for NKX2.2 and NKX3.1. By FISH both cases demonstrated convincing break-apart signals of CIC gene. One patient died of disease after 1 month, and the other died of disease after 3 months. Conclusions: CRS is a small round cell undifferentiated sarcoma of the bone and soft tissue defined by molecular genetic characteristics, and may show atypical morphologic and immunophenotypic characteristics such as rhabdoid features. A correct understanding of its rare morphologic and immunophenotypic characteristics, combined with molecular pathologic detection, is conducive to correct diagnosis.