[Clinical analysis of cytomegalovirus infection-associated hemophagocytic lymphohistiocytosis in five patients without underlying diseases].

The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.

[Effect of Friday surgery on clinical outcome of elderly patients with hip fracture under multidisciplinary treatment].

Objective: To assess the impact of Friday surgery on clinical outcomes in elderly patients with hip fracture under multidisciplinary treatment. Methods: A retrospective cohort study. The clinical data of 414 geriatric patients with hip fractures admitted to Zhongda Hospital Affiliated with Southeast University from January 2018 to March 2021 were analyzed retrospectively, including 126 males and 288 females with a mean age of (81.3±7.6) years. The patients were divided into two groups based on whether they underwent surgery on Friday or not. The Friday group(n=69) and the non-Friday group(n=345) were compared in terms of general information, American Society of Anesthesiologists(ASA) classification, fracture type, injury to admission time, preoperative waiting time, surgical method, anesthesia type and use of intensive care unit (ICU) fast track. Propensity score matching (PSM) was performed based on age, ASA grade, time from injury to admission, preoperative waiting time, hemoglobin and albumin levels at admission. Clinical outcomes were collected and compared between the two groups, including length of hospital stay, total hospitalization cost and 30-day, 90-day and 1-year mortality rates, and postoperative complications. Multivariate logistic regression analyses were conducted to identify influencing factors for 1-year mortality in geriatric patients with hip fracture. Results: Baseline data showed statistically significant differences in hemoglobin, albumin and preoperative waiting time between the two groups (all P<0.05). After PSM matching, 69 patients were included in each group, and no significant differences were observed in baseline data between the two groups (all P>0.05). There was no significant differences in 30-day mortality rate (4.3% vs 0, P=0.080), 90-day mortality rate (7.2% vs 1.4%, P=0.095), length of hospital stay [(10.85±4.45)d vs (10.92±3.68)d, P=0.919], total hospitalization cost [(60.9±15.4) thousands yuan vs (59.1±15.4) thousands yuan, P=0.489], postoperative complications [pneumonia (11.6% vs 13.0%, P=0.796), cardio-cerebrovascular complications (11.6% vs 8.7%, P=0.573) and delirium (5.7% vs 2.9%, P=0.245)] between the Friday group and the non-Friday group (all P>0.05). However, the 1-year mortality rate was higher in the Friday group than that in the non-Friday group(18.8% vs 4.3%, P=0.008). Multivariate analysis revealed that surgery on Friday (OR=11.222, 95%CI: 2.198-57.291, P=0.004), low hemoglobin levels at admission (OR=0.920, 95%CI: 0.875-0.967, P=0.001), hemiarthroplasty treatment (OR=5.127, 95%CI: 1.308-20.095, P=0.019) and longer surgery duration (OR=0.958, 95%CI: 0.927-0.989, P=0.009) were influencing factors for 1-year mortality in geriatric patients with hip fracture. Conclusions: In the context of multidisciplinary treatment, Friday surgery does not increase short-term mortality, length of hospital stay, total hospitalization cost or incidence of complications in geriatric patients with hip fracture. However, it remains a influencing factor for 1-year mortality in those patients.

[Clinicopathological analysis of benign mammary ductal cystic papillomatosis with loss of myoepithelial cells].

Objective: To investigate the histopathological and immunohistochemical characteristics of benign apocrine cystic papillary hyperplasia of the breast with loss of myoepithelial cell layer. Methods: The clinical data, histopathological features and immunohistochemical profile of patients with benign apocrine cystic papillary hyperplasia of breast with loss of myoepithelial cell layer from January 2016 to December 2021 were examined, in which six patients were identified. Results: All six patients were female, aged 36-61 years (median 46 years), who presented with a breast mass; three cases were from the left breast and three cases were from the right breast. Microscopic examination of all cases showed breast hyperplasia with apocrine cysts, accompanied by different degrees of micropapillary and papillary hyperplasia of apocrine cells. One case was associated with lobular carcinoma in situ, and one case was associated with apocrine ductal carcinoma in situ with intraductal dissemination in adenosis. Immunohistochemical staining of CK5/6, p63, SMA, SMMHC, Calponin and CD10 showed complete absence of myoepithelial cell layer surrounding ducts in apocrine cystic papillary hyperplasia. Conclusions: The myoepithelial cells of apocrine cystic papillary hyperplasia of the breast may undergo abnormal changes and may even be completely lost. The diagnosis should be comprehensively considered along with cytomorphological and histological features to avoid overdiagnosis.

[Expression of PD-L1 and tumor infiltrating lymphocyte markers in uterine cervical carcinoma].

Objective: To investigate the expression of PD-L1, CD4, CD8 and CXCL-13 in cervical carcinoma, and their clinicopathological significance was analyzed. Methods: A total of 77 patients with cervical carcinoma in the Seventh Medical Center, PLA General Hospital from January 2019 to December 2021 were included. All patients received radical surgical resection in the Seventh Medical Center of Chinese PLA General Hospital. The expression of PD-L1, CD4, CD8 and CXCL-13 was detected by immunohistochemical (IHC) method. The correlation between IHC markers and patients' clinicopathological parameters was analyzed. Results: There were 59 cases of squamous cell carcinoma and 18 cases of adenocarcinoma (ranging from 29 to 69 years) with an average of (49.4±9.8) years. PD-L1 was expressed in different degrees in cervical squamous cell carcinoma and adenocarcinoma (χ²=4.975, P=0.026); CD4+, CD8+and CXCL-13+tumor infiltrating lymphocytes (TIL) were observed in the carcinoma cell nests and peritumoral stroma. PD-L1 expression in cervical carcinoma was moderately correlated with the number of CD4+TIL in the carcinoma nests, and the number of CD8+, CXCL-13+TIL infiltration in the carcinoma nests and stroma, but not to the patient's age, histologic differentiation, presence or absence of vascular invasion, presence or absence of lymph node metastasis and FIGO stage (P>0.05). Conclusions: The high expression of PD-L1 in cervical carcinoma tissues is closely related to the number of TIL in the carcinoma nests and peritumor stroma, suggesting that they may have important reference value for predicting the response to immunotherapy in patients with cervical carcinoma.

[Clinical application of vitrification freezing of oocytes].

Objective: To evaluate the effect of oocyte vitrification on embryo quality and developmental potential. Methods: From January 2014 to December 2017, 30 cases of oocytes vitrification in the reproductive center of Sir Run Run Shaw hospital were collected as the frozen group, due to failure of sperm extraction or inability to obtain sufficient sperm at the ovum pick-up-day because of oligoospermia or azoospermia. 220 cases of fresh oocytes from the same period were selected as the fresh group. The fertilization rate, embryo rate, pregnancy rate, implantation rate and live birth rate of the two groups were compared retrospectively. Results: The survival rate of oocyte resuscitation was 91.4% (180/197). In the frozen group, 24 cases were transferred with 14 pregnancies, while in the fresh group, 31 cases were transferred with 18 pregnancies. The number of 2PN fertilized eggs, 2PN embryos and 2PN high-quality embryos in the frozen group was significantly lower than that in the fresh group (3.7±2.5 vs 7.3±4.8), (3.3±2.5 vs 7.2±4.8), and (1.2±1.8 vs 2.9±2.7) (all P<0.05). The fertilization rate of the frozen group was 77.2% (115/149) and the high-quality embryo rate was 36.6% (37/101), lower than that of the fresh group 77.6% (1 637/2 109) and 40.9% (651/1 591) (P>0.05).The pregnancy rate of the frozen group was 58.3% (14/24) higher than that of the fresh group 58.1% (18/31), the implantation rate of each mature oocyte and the live birth rate of each mature oocyte were 10.8% (15/138) and 10.8% (15/138), both higher than that of the fresh group 9.6% (21/218) and 8.7% (19/218) (all P>0.05). Conclusions: Vitrification cryopreservation of oocytes may lead to a decrease in embryo quality, but embryo development potential is still considerable. Higher pregnancy rate, implantation rate and live birth rate may be obtained.

[The value of conventional magnetic resonance imaging based radiomic model in predicting the texture of pituitary macroadenoma].

Objective: To investigate the value of conventional magnetic resonance imaging (MRI) based radiomic model in predicting the texture of pituitary macroadenoma. Methods: The complete data of 101 patients with pituitary macroadenoma confirmed by surgery and pathology in Yijishan Hospital of Wannan Medical College from December 2014 to December 2019 were retrospectively analyzed. According to the texture of the intraoperative pituitary tumor, patients were divided into soft group (n=58) and hard group (n=43). They were randomly divided into training group (n=72) and validation group (n=29) at a ratio of 7∶3. All patients underwent conventional MRI scan of the pituitary gland. Itk-snap software was used to manually outline the T(1)-weighted image (T(1)WI), T(2)-weighted image (T(2)WI) and enhanced T(1)WI image section by section on tumor area of interest (ROI) and perform three-dimensional fusion. Then AK software was imported to extract texture features. The regression analysis methods of minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used for feature selection and radiomic signature establishment. The reliability of the model was verified by 100 leave-group-out cross validation (LGOCV), and the predictive ability of the model was evaluated by drawing the receiver operating characteristic (ROC) curve. The decision curve analysis (DCA) was used to evaluate the clinical application value of the model. Results: The AUC (Area Under the ROC Curve) (95%CI) values of T1WI, T2WI, enhanced T1WI, and the combined sequence model to predict the texture of pituitary macroadenomas in the training and validation groups were 0.91 (0.84-0.98) and 0.90 (0.78-1.00), 0.86 (0.78-0.95) and 0.83 (0.64-1.00), 0.90 (0.83-0.97) and 0.89 (0.77-1.00),0.92 (0.85-0.98) and 0.91 (0.79-1.00), respectively. DCA demonstrated that T(1)WI, T(2)WI, enhanced T(1)WI, and combined sequence model all had good net benefits in clinical practice. Conclusions: T(1)WI, T(2)WI, enhanced T(1)WI, and combined sequence model of conventional MRI all had high efficacy in predicting the texture of pituitary macroadenoma, which provided a new quantitative method for predicting the texture of pituitary macroadenoma.

[Co-culture with endometrial stromal cells promotes the differentiation of menstrual blood-derived mesenchymal stem cells into endometrial epithelial cells].

Objective: To study the potential of differentiation of menstrual blood-derived mesenchymal stem cells (MenSC) into endometrial epithelial cells (EEC) in vitro. Methods: Endometrial stromal cells (ESC) and MenSC were cultured and identified by certain methods.MenSC were co-cultured with ESC, added 10 ng/ml TGF-ß1, 10 ng/ml EGF, 10 ng/ml PDGF-BB and 1×10(-7) mol/L 17-ß-estradiol.The expression of cytokeratin, which was marker of EEC, was tested by immunofluorescence in differentiated MenSC. Results: MenSC proliferated quickly in vitro, and showed fusiform shape and clear structure within 10 generations.The expression rate of superficial markers of MenSC, CD44, CD90, CD73, and CD29, were 98.4%, 90.77%, 94.75% and 97.01% respectively.The expression of vimentin, which was stromal marker, was positive in cultured ESC (P3). After co-cultured with ESC for 3 weeks, MenSC morphology changed from fibroblast-like cells into epithelial-like cells.Immunofluorescence assay showed that the differentiated MenSC expressed cytokeratin. Conclusion: Under the condition of co-culture with ESC, MenSC has the ability to differentiate into endometrial epithelial cells. Cell growth factor and estrogen play the important roles in this process.

Novel Polymorphisms of Adrenergic, Alpha-1B-, Receptor and Peroxisome Proliferator-activated Receptor Gamma, Coactivator 1 Beta Genes and Their Association with Egg Production Traits in Local Chinese Dagu Hens.

Adrenergic, alpha-1B-, receptor (ADRA1B) and peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B) genes are involved in regulation of hen ovarian development. In this study, these two genes were investigated as possible molecular markers associated with hen-housed egg production, egg weight (EW) and body weight in Chinese Dagu hens. Samples were analyzed using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, followed by sequencing analysis. Two novel single nucleotide polymorphisms (SNPs) were identified within the candidate genes. Among them, an A/G transition at base position 1915 in exon 2 of ADRA1B gene and a T/C mutation at base position 6146 in the 3'-untranslated region (UTR) of PPARGC1B gene were found to be polymorphic and named SNP A1915G and T6146C, respectively. The SNP A1915G (ADRA1B) leads to a non-synonymous substitution (aspartic acid 489-to-glycine). The 360 birds from the Dagu population were divided into genotypes AA and AG, allele A was found to be present at a higher frequency. Furthermore, the AG genotype correlated with significantly higher hen-housed egg production (HHEP) at 30, 43, 57, and 66 wks of age and with a higher EW at 30 and 43 wks (p<0.05). For the SNP T6146C (PPARGC1B), the hens were typed into TT and TC genotypes, with the T allele shown to be dominant. The TC genotype was also markedly correlated with higher HHEP at 57 and 66 wks of age and EW at 30 and 43 wks (p<0.05). Moreover, four haplotypes were reconstructed based on these two SNPs, with the AGTC haplotype found to be associated with the highest HHEP at 30 to 66 wks of age and with higher EW at 30 and 43 wks (p<0.05). Collectively, the two SNPs identified in this study might be used as potential genetic molecular markers favorable in the improvement of egg productivity in chicken breeding.

[MRI features of ventricular system tuberculosis].

OBJECTIVE: To study the MRI features of ventricular system tuberculosis. METHODS: Nineteen patients with ventricular system tuberculosis in our hospital from Mar. 2009 to Sep. 2014 were retrospectively identified. Their clinical features and cranial MRI characteristics were reviewed. RESULTS: There were 13 males and 6 females, aged from 15-81 years(mean 37±16). Eight patients had intraventricular tuberculosis, with 5 long striped or irregular shaped intraventricular tuberculosis and 3 with ventricular tuberculoma. Six patients had tubercular ependymitis and 5 had intraventricular tuberculosis along with tubercular ependymitis. The lesions of 14 patients were in the lateral ventricle; 13 in occipital or temporal horn of lateral ventricle, 9 complicated by tubercular meningitis, and 10 complicated by brain tuberculoma. The lesion of 5 patients were in the fourth ventricle, 5 in the postmedian of the fourth ventricle, 5 complicated by tubercular meningitis and 4 complicated by hydrocephalus. There were 4 cases with ring-enhancement and 15 with heterogeneous enhancement. Ten cases were complicated by peripheral edema. CONCLUSIONS: The diagnosis of ventricle system tuberculosis is difficult due to its low incidence. The site, cranial MRI characteristics, the patterns of enhancement and complications have certain specificity and are useful in the diagnosis of ventricular system tuberculosis.

MicroRNA-141 regulates the tumour suppressor DLC1 in colorectal cancer.

Our previous study has showed that DLC1 acts as a functional tumor suppressor in colorectal cancer (CRC) cell lines. The aims of this study were to determine whether DLC1 is a target of MicroRNA (miRNA) regulation and to evaluate the role of this mechanism in CRC. By bioinformatics approach and literature, miR-141 was chosen for further study. The miR-141 mimic, miR-141 inhibitor were synthesized and transfected to Lovo cells. Cell growth was determined by MTT and in vivo models. The flow cytometric analysis for cell cycle determination and transwell assays for evaluating the cell invasion were used. Luciferase reporter assays and Western blots showed that DLC1 was a direct target of miR-141 in CRC. The expression levels of miR-141 were obviously up-regulated in CRC tissues compared to non-cancerous tissues, while DLC1 expression levels were down-regulated in a high proportion of clinical samples (14/18). In addition, correlation analyses revealed negative correlation between miR-141 levels and DLC1 expression levels in CRC tissues. MiR-141 overexpression promoted cell growth in vitro and in vivo, promoted cell cycle progression and invasion in Lovo cells. Furthermore, re-introduction of DLC-1 in miR-141-overexpressing Lovo cells decreased growth rate of cells, increase of the percentage in G0/G1 phase and decreased the number of migrating cells. In conclusion, we demonstrated that miR-141 is up-regulated in CRC and acts as a functional oncogene by targeting DLC1.

Association between ADSL, GARS-AIRS-GART, DGAT1, and DECR1 expression levels and pork meat quality traits.

In this study, meat quality traits were compared between Chinese lard- and European lean-type pigs. The association between expression of four genes (ADSL, GARS-AIRS-GART, DGAT1, and DECR1) and meat quality traits was also investigated. Meat quality traits were found to differ significantly between pig breeds. Meat color parameter values (a* and b*) and intramuscular fat content in Anqingliubai were significantly higher than those in Landrace (P < 0.01). Meat pH at 1 and 24 h following slaughter was significantly higher in Landrace than in Wei pigs, and meat inosine monophosphate (IMP) content was significantly higher in Landrace than in Wei and Anqingliubai pigs (both P < 0.01). Expression levels of ADSL, GARS-AIRS-GART, and DGAT1 were higher in longissimus lumborum muscle than in heart or liver tissues. ADSL and GARS-AIRS-GART expression levels were correlated with meat IMP content and pH levels. The results of this study will contribute to the understanding of meat quality traits in Chinese lard- and European lean-type pigs.

Relationship between polymorphisms in exon 10 of FSHR gene and litter size in swine.

Follicle-stimulating hormone (FSH), a glycoprotein secreted by the anterior pituitary, can regulate ovarian function through the FSH receptor (FSHR). To evaluate the effects of the FSHR gene on reproductive traits in pigs, polymorphisms in exon 10 of the FSHR gene were observed by polymerase chain reaction-single-strand conformation polymorphism, and 3 single nucleotide polymorphisms (C1491T, G1885A, and C1977T) in exon 10 of the porcine FSHR gene, and 3 genotypes (AA, AB, and BB) for C1491T and 2 haplotypes (D and E) for G1885A and C1977T were identified. Further analysis of single nucleotide polymorphism genotypes associated with reproductive traits including total number born (TNB) and number born alive (NBA) was carried out in 3 pig populations including Berkshire, Wannan Black (a Chinese indigenous pig breed), and BW pigs (two-way crossbred pigs produced from Berkshire ♂ and Wannan Black pig ♀). The results showed that the TNB and NBA of Wannan Black pigs with the AB genotype were significantly higher than in AA genotype sows (P < 0.01) in multiparity sows and all parities. The TNB and NBA of Berkshire pigs with the DE genotype were significantly higher than the DD and EE genotype sows (P < 0.01) in gilts, sows and all parities. Overall, TNB and NBA from the 3 identified genotypes was DE > DD > EE. The results showed that polymorphisms in exon 10 of the FSHR gene had a significant effect on litter size traits of Wannan Black and Berkshire pigs. These results can be applied for marker-assisted selection in the 2 swine breeds.

Cystic fibrosis transmembrane conductance regulator is correlated closely with sperm progressive motility and normal morphology in healthy and fertile men with normal sperm parameters.

Cystic fibrosis transmembrane conductance regulator (CFTR) has been demonstrated to be expressed in mature spermatozoa and correlated with sperm quality. Sperm CFTR expression in fertile men is higher than that in infertile men suffering from teratospermia, asthenoteratospermia, asthenospermia and oligospermia, but it is unknown whether CFTR is correlated with sperm parameters when sperm parameters are normal. In this study, 282 healthy and fertile men with normal semen parameters were classified into three age groups, group (I): age group of 20-29 years (98 cases, 27.1 ± 6.2), group (II): age group of 30-39 years (142 cases, 33.7 ± 2.6) and group (III): age group of more than or equal to 40 years (42 cases, 44.1 ± 4.6). Sperm concentration, total count and progressive motility were analysed by computer-assisted sperm analysis. Sperm morphology was analysed by modified Papanicolaou staining. Sperm CFTR expression was conducted by indirect immunofluorescence staining. There was a significant positive correlation (P < 0.001) between CFTR expression and sperm progressive motility (r = 0.221) and normal morphology (r = 0.202), but there were no correlations between sperm CFTR expression and semen volume, sperm concentration, sperm total count as well as male age (P > 0.05). Our findings show that CFTR expression is associated with sperm progressive motility and normal morphology in healthy and fertile men with normal sperm parameters, but not associated with the number of spermatozoa and male age.

[Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia].

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Production of secoisolariciresinol from defatted flaxseed by bacterial biotransformation.

AIMS: Secoisolariciresinol (SECO) is increasingly recognized for potential clinical application because of its preventive effects against breast and colon cancers, atherosclerosis and diabetes, and its production through biotransformation has been attempted. However, previously reported bacteria all required stringent anaerobic culture conditions, precluding large-scale production. Here, we report the isolation and characterization of bacteria that produce SECO under less stringent anaerobic culture conditions. METHODS AND RESULTS: Using defatted flaxseed as raw material, we isolated a facultative anaerobic bacterium from human faeces that hydrolysed secoisolariciresinol diglucoside-3-hydroxy-3-methyl glutaric acid (SDG-HMGA) oligomers in flaxseed to produce SECO. Both conventional assays and 16S rRNA gene sequence analysis demonstrated its close relatedness with Bacteroides uniformis. The transformation efficiency of SDG in defatted flaxseed to SECO was more than 80% by this bacterial strain. We investigated factors that might influence fermentation, such as redox potential and pH, for large-scale fermentation of defatted flaxseed to produce SECO. CONCLUSIONS: The method to produce SECO through biotransformation of defatted flaxseed with this bacterial strain is highly efficient and economic. SIGNIFICANCE AND IMPACT OF THE STUDY: This bacterial strain can transform SDG to SECO under less stringent anaerobic culture conditions, which will greatly facilitate industry-scale production of SECO.

[Clonality relatedness and molecular characteristics of Richter transformation].

Objective: To investigate the clinical, genetic, and clonality related aspects of individuals with Richter transformation (RT) . Methods: From January 2019 to December 2021, 18 RT patients with diagnoses at the First Affiliated Hospital of Nanjing Medical University (Pukou CLL center) were retrospectively examined. The immunoglobin heavy variable (IGHV) gene usage and IGHV-D-J rearrangement pattern of diagnosed CLL/SLL and transformed diffuse large B-cell lymphoma (DLBCL) were compared to determine the clonality relatedness. To investigate the risk factors of RT, Clinical and laboratory data from patients with newly diagnosed CLL/SLL and transformed DLBCL were gathered. Results: The median age of RT was 56.5 (41-75) years old. 17 patients transformed to DLBCL and 1 transformed to Hodgkin lymphoma (HL) . Of 17 individuals who had DLBCL transformation, 15 had CLL/SLL-related clonality and 2 had unrelated clonality. Next-generation sequencing (NGS) analysis of 11 paired initially diagnosed treatment-naive CLL/SLL and RT DLBCL found that EGR2、TP53 and NOTCH1 were among the most frequently mutated genes both in treatment-naive CLL/SLL and in RT DLBCL. In several cases, specific mutations were gained or lost throughout RT, indicating clonal evolution. Among 10 patients before exposure to BTK inhibitors before RT, four patients acquired BTK mutation. The aforementioned mutations should be considered high-risk variables for transformation; in addition, TP53 and EGR2 mutations could be linked to a poor prognosis following RT in patients receiving a cocktail of new medicines. Conclusion: Most RT DLBCL patients in our center are clonality related (15/17, 88.2% ) and we recommend all qualified centers to evaluate clonality relatedness of RT DLBCL patients. There was some variability in the mutational landscape between DLBCL that had undergone a transformation and initially diagnosed, treatment-naive CLL/SLL. The underlying molecular mechanism of RT needs more research.

Analysis of the clinicopathological characteristics and prognosis of adenoid cystic carcinoma of the intraoral minor salivary glands: a retrospective study of 40 cases.

The clinicopathological aspects and prognostic factors of 40 patients with adenoid cystic carcinoma (ACC) of the intraoral minor salivary glands, treated between 2007 and 2017 at a single institution, were evaluated retrospectively. Twenty-six were female and 14 were male, and they ranged in age from 26 to 81 years (median 55 years). ACC occurred mainly in the palate, with 54.8% of cases presenting T3-T4 lesions. Curative surgery was performed in all patients, and 62.5% of patients were treated with postoperative adjuvant radiotherapy. In the final analysis, positive surgical margins were noted in 57.5% of cases and perineural invasion in 70%. Follow-up was at least 13 months (range 13-141 months, median 59 months). Nineteen patients (47.5%) developed recurrent disease after initial surgery and nine patients had died at the end of follow-up. The 5- and 10-year overall survival rates were 88.3% and 25.6%, respectively. The 5- and 10-year disease-free survival rates were 75.6% and 34.0%, respectively. Patients with a tumour size >4cm and those with positive surgical margins showed a significantly higher risk of local recurrence. Elective neck dissection is suggested for patients with clinically positive lymph nodes or a locally advanced tumour, especially those undergoing microvascular reconstruction. The survival analysis results are similar to those reported previously in the literature.

Combination therapy with interleukin-15 and metformin as a synergistic treatment for pancreatic cancer.

OBJECTIVE: To investigate the efficacies and mechanisms of combination therapy with interleukin-15 (IL-15) and metformin (Met) on suppressing pancreatic cell proliferation and protecting Panc02-bearing mice. MATERIALS AND METHODS: MTT assays were applied to assess the inhibitory effects of IL-15 combined Met or Met and IL-15 alone on proliferation of normal HPDE6-C7 and Panc02 cells. After tumor grew up to 150 mm3, the Panc02-bearing xenograft model mice were randomly divided into saline group, IL-15 and Met alone group and combined treatment group (n=8) with the administration of each agent every other day for three weeks, and survival rates were recorded. The changes in tumor size, expression levels of the apoptosis, autophagy as well as Akt/mTOR/STAT3-related factors in tumor tissues were all measured. RESULTS: MTT assays demonstrated significantly inhibiting efficacy of combination therapy with IL-15 and Met on Panc02 cell proliferation compared to other groups (all p<0.05) with combination index<1 showing evident synergistic effect. Moreover, the apoptosis rate of Panc02 cell under combined treatment were 95.5±3.2% and significantly higher than those of others (all p<0.01). In addition, combined administration remarkably inhibited the growth of pancreatic carcinoma, and improved survival rate of Panc02-bearing model with less body weight loss. Furthermore, combined treatment significantly downregulated anti-apoptotic proteins as well as Akt/mTOR/STAT3 signaling pathway and upregulated autophagy related factors, respectively, compared with those of monotherapy groups in both Panc02 cells and tumor tissues. CONCLUSIONS: Combined treatment of IL-15 with Met showed synergistic anti-tumor efficacies on Panc02 cells attributing to promotion on apoptosis, autophagy and inhibition on Akt/mTOR/STAT3 signaling-transduction in Panc02-bearing model mice.

[Comparison of four prognostic scoring system in patients with early asymptomatic chronic lymphocytic leukemia patients].

Objective: To compare the prognostic value of four prognostic models in predicting time to first treatment (TTFT) in patients with Binet A Chinese chronic lymphocytic leukemia (CLL) . Methods: This retrospective analysis included one hundred and ten patients with Binet A CLL, initially diagnosed in the First Affiliated Hospital of Nanjing Medical University (Pukou CLL center) from June 2009 to January 2020. Risk stratification was conducted according to IPS-E, CLL-IPI, CLL1-PM, and Barcelona-Brno prognostic models. Results: Among 110 patients with Binet A CLL patients, the median age was 58 (25-84) years. The median follow-up time was 35 (4-189) months, and 57 (51.8%) patients met the indication for treatment due to symptomatic disease progression during follow-up. Log-rank analysis of nine variables was conducted involving age, Rai stage, absolute lymphocyte count (ALC) , lymph node size, lymphocyte doubling time (LDT) , ß(2)-Microglobulin, IGHV status, TP53, and Del (11q) . Additionally, Rai Ⅰ-Ⅲ, ALC>15×10(9)/L, palpable lymph node size ≥1cm, ß(2)-Microglobulin>3.5 mg/L, unmutated IGHV, TP53 mutation or deletion, and 11q deletion were independent risk factors of TTFT. Predictive value of each model was assessed by Harrel C-index and Akaike information criterion (AIC) with CLL1-PM (C-index=0.736, AIC=777) , followed by CLL-IPI (C-index=0.722, AIC=933) , IPS-E (C-index=0.683, AIC=1004) , and Barcelona-Brno prognostic model (C-index=0.663, AIC=986) . Conclusion: All four prognostic models effectively predicted TTFT. IPS-E might be an ideal model to guide clinical surveillance because of its easy accessibility and low expenses in routine clinical practice. Therefore, for patients receiving fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) examination at diagnosis, CLL-IPI or CLL1-PM could be applied to evaluate their prognosis more comprehensively.