[Research progress in the diagnosis and treatment of childhood glaucoma].

Childhood glaucoma is a disease that seriously endangers children's visual health. It will accompany the patients throughout their lives and bring a heavy burden to families and society. Most childhood blindness caused by glaucoma is preventable or treatable. Relevant research has made progress in recent years. Based on the new consensus reached by the World Glaucoma Association and the latest medical evidence at home and abroad, this article summarizes the definition, classification, diagnosis, molecular genetics, pathogenesis and comprehensive treatments including drugs and surgery of childhood glaucoma, with a focus on the application of various surgical methods, so as to provide reference for clinical and scientific research and improve the clinical diagnosis and treatment of childhood glaucoma.

[Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment].

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

[Current status of ophthalmic case registration study in the setting of real world study].

A new research concept has emerged in recent years, called real world study (RWS), which mainly relies on registration study and data management, and aims to evaluate the real effects and risks of actual clinical practice or health examination. This article compares the differences between RWS and randomized controlled trials, and summarizes the current situation of registration study in the medical field of RWS domestic and abroad, especially the current progress in the ophthalmic field. It is expected more medical centers will be able to conduct follow-ups based on the case registration system and carry out multicenter, large-scale RWS in the future.

[Changes of the World Health Organization 2022 classification (5th edition) of salivary glands tumors].

Pathological diagnosis of salivary gland tumors is one of the most challenging areas in all head and neck surgical pathology. The classification of salivary gland tumors was updated in the 5th edition of the World Health Organization Classification of Head and Neck Tumours, most of which were based on their molecular pathological characteristerics. This new classification features a description of several new entitiesamong benign and malignant neoplasms, salivary gland tumors with updated naming or diagnostic criteria, and lesions deleted from this section, etc.This present review focuses on the updates and changes in the new classification of salivary gland tumors, and provides some reference for head and neck surgeons and pathologists.

[P2X7R promotes migration and invasion of Lewis lung cancer cells by activating the AKT signaling pathway].

OBJECTIVE: To explore the role of P2X7 receptor (P2X7R) in migration and invasion of mouse Lewis lung cancer (LLC) cells and examine the tumorigenic ability of LLC cells in P2X7R-knockout mice. METHODS: RT-PCR was used to examine P2X7R mRNA expression in LLC cells. LLC cells were treated with ATP (as a P2X7R agonist) or 2'- 3'- O- (4-benzoyl- benzoyl)-ATP (BzATP) (a P2X7R agonist) with or without pretreatment with P2X7R antagonist oxATP or A438079. The changes in migration and invasive abilities of the cells were evaluated using wound healing assay and Transwell assay; Western blotting was performed to determine the activation level of the key proteins in the AKT signaling pathway. The effects of BzATP, A438079, and LY294002 (a inhibitor of the PI3K/AKT pathway) on migration and invasion of LLC cells were also examined. In wild-type (WT) and P2X7R knockout (P2X7-/-) C57BL/6 mice, the growth of subcutaneous LLC cell xenografts were observed by measuring tumor volume and weight. RESULTS: P2X7R expression was detected in LLC cells. Treatment with P2X7R agonist significantly enhanced migration and invasion abilities of LLC cells, and this effect was inhibited by application of P2X7R antagonists (P < 0.001). Western blotting showed that BzATP treatment of LLC cells significantly increased the expression level of p-AKT protein, which was obviously lowered by treatment with P2X7R antagonist (P < 0.01). P2X7R antagonist strongly inhibited BzATP-induced enhancement of LLC cell migration and invasion (P < 0.001). In the tumor- bearing mice, the tumor volume and weight were significantly lower in P2X7-/- mice than in WT mice (P < 0.05). CONCLUSION: P2X7R promotes migration and invasion of LLC cells by activating the AKT signaling pathway, and LLC cells show lowered tumorigenic capacity in P2X7-/- mice.

[Glaucoma secondary with juvenile xanthogranuloma in children:a case report].

A 4-month-old boy was admitted to the hospital after his parents noticed fog in his right eye for 27 days. Physical examination revealed multiple light brown macules on the skin. The intraocular pressure (IOP) of the right eye was 34.4 mmHg (1 mmHg=0.133kPa) and the corneal was enlarged and edema while the aqueous humor was cloudy with blood in the right eye. Yellow peripheral anterior synechia was seen on the temporal and inferior iris. Ultrasound biomicroscopy (UBM) showed extensive adhesion closure of the anterior chamber angle and the local thicken iris with the nodule. No obvious abnormality was observed in the left eye. It was confirmed as juvenile xanthogranuloma by skin lesion biopsy. IOP was normal after systemic and local therapy with corticosteroids and local IOP lowering medication. Follow up 35 months, IOP is normal without medication.

[The correlation of CD49d expression pattern with molecular genetics and hotspot gene mutants in patients with chronic lymphocytic leukemia].

Objective: To explore the correlation of CD49d expression patterns with molecular genetics and hotspot gene mutants in patients with chronic lymphocytic leukemia. Methods: The expression of CD49d was detected by flow cytometry and grouped into homogeneous, bimodal, negative and positive expression. Panel fluorescence in situ hybridization (FISH) was used for molecular genetics analysis and next-generation sequencing (NGS) was conducted for gene mutation detection. Results: There were 43 patients (23.89% ) with positive CD49d expression, 137 patients (76.11% ) with negative CD49d expression, 96 patients (53.33% ) with homogeneous CD49d expression and 84 patients (46.67% ) with bimodal CD49d expression. Compared with patients in the CD49d negative group, patients in the CD49d positive group had higher Rai stage (P=0.048) and higher proportion of spleen enlargement (P=0.030) . Compared with patients with homogeneous expression of CD49d, patients with bimodal expression of CD49d had a higher proportion of spleen enlargement (P=0.009) . The expression rate of 11q22- in bimodal CD49d(-) group was significantly higher than that in homogeneous CD49d(-) group (24.29% vs 10.45% , P=0.043) . The incidence of +12 in homogeneous CD49d group was higher than that in bimodal CD49d group (16.67% vs 5.95% , P=0.035) . The incidence of +12 in homogeneous CD49d(+) group was higher than that in bimodal CD49d(-) group (17.24% vs 4.29% , P=0.045) . The incidence of +12 in homogeneous CD49d(-) group was higher than that in bimodal CD49d(-) group (16.42% vs 4.29% , P=0.024) . BIRC3 mutation rate in CD49d positive group was higher than that in CD49d negative group (11.63% vs 2.92% , P=0.037) . Conclusion: There were significant correlations between CD49d and 11q22-, +12 and BIRC3 gene mutation. Patients with bimodal CD49d were more correlated with poor prognosis indexes.

[Study of cytogenetics and molecular biology in typical and atypical immunophenotypic chronic lymphocytic leukemia].

Objective: To analyze the differences in immunophenotype, cytogenetics, and molecular biology between typical and atypical immunophenotype chronic lymphocytic leukemia (CLL) , and explore the correlation of cytogenetic anomalies with gene mutations. Methods: This study included 488 patients diagnosed in the First Affiliated Hospital of Nanjing Medical University between November 2014 and May 2021. Of these, 382 patients scored 4-5 points, which was typical CLL (tCLL) , and 106 scored 3 points, which was atypical CLL (aCLL) as per the Royal Marsden Hospital Immunomarker Integral System. Peripheral blood cells were collected for immunophenotype by multiparameter flow cytometry in 488 patients, fluorescence in situ hybridization (FISH) was employed to detect cytogenetic anomalies in 359 patients, and gene mutations were detected by next-generation sequencing (NGS) in 330 patients. Results: The positive rates of CD10, CD22, CD49d, CD81, and FMC7 were significantly higher in the aCLL compared with the tCLL group (P=0.020, P<0.001, P<0.001, P=0.027, and P<0.001, respectively) , while the positive rates of CD5, CD23, CD148, and CD200 were lower in the former compared to the latter (P<0.001, P=0.017, P=0.041, and P<0.001, respectively) . aCLL exhibited a higher frequency of trisomy 12 and lower frequency of del (13q14) compared to the tCLL group (P<0.001 and P<0.001, respectively) . Moreover, aCLL patients also showed a higher incidence of NOTCH1 mutations than the tCLL patients (P=0.038) , while no statistically significant differences in other gene mutations occurred between the two groups. No significant differences in overall survival (OS) and treatment-free survival (TFS) occurred between aCLL and tCLL using Kaplan-Meier analysis (P>0.05) . Conclusion: aCLL has characteristic immunophenotype, cytogenetic, and somatic mutation that differ from tCLL, and this can provide reliable information for the diagnosis and differential diagnosis between the two groups.

[Comparison study for the proportion of underdiagnosed zonulopathy in angle closure glaucoma].

Objective: To analyze the proportion and clinical characteristics of underdiagnosed zonulopathy in angle closure glaucoma (ACG) patients and to explore the related risk factors. Methods: Case-control study. Continuous cases of ACG patients who underwent phacoemulsification combined with intraocular lens implantation and goniosynechialysis surgery [ACG group, including acute angle closure glaucoma (AACG) and chronic angle closure glaucoma (CACG)] from November 1, 2020 to October 31, 2021 and age-related cataract patients who underwent phacoemulsification combined with intraocular lens implantation surgery in the same period (control group) were included. The diagnosis of zonulopathy was determined according to the intraoperative signs such as wrinkles of the anterior capsule during continuous circular capsulorhexis. The proportion of zonulopathy, preoperative diagnosis rate of zonulopathy, demographic characteristics, anterior chamber depth (ACD), axis length, difference of ACD in both eyes (ACD of the contralateral eye minus ACD of the operated eye) were compared between the two groups. The related risk factors were explored. The paired t-test (comparison between two groups of normally distributed data), non-parametric test (comparison between two groups of non-normally distributed data), Chi-square test (categorical variables), univariate and multivariate logistic regression analysis were used. Results: There were 104 ACG patients (104 eyes), including 63 AACG patients (63 eyes) and 41 CACG patients (41 eyes), and 117 controls (117 eyes). There was no significant difference in age (P=0.29) and gender (P=0.07) between the two groups. The ACG group had shallower anterior chamber (P<0.001), shorter axial length (P<0.001) and more ACD difference in both eyes (P<0.001). In the ACG group, the proportion of zonulopathy was 46.2% (48/104), which was significantly higher than that (6.0%, 7/117) in the control group (P<0.001). In the control group, only zonular laxity was found, while in the ACG group, besides the predominant zonular laxity (68.8%, 33/48), there was zonular dehiscence (31.3%, 15/48). The eyes with AACG (57.1%, 36/63) had a higher proportion of zonulopathy than those with CACG (29.3%, 12/41) (P=0.006). In the ACG group, only 14 cases (29.8%) were diagnosed preoperatively according to slit lamp examination and/or ultrasound biomicroscopy. The proportion of underdiagnosed zonulopathy was 70.8% in the ACG group (34/48). A smaller ACD was found to be related to the zonulopathy in the ACG group. All AACG cases with an ACD ≤2.0 mm and CACG cases with an ACD ≤1.9 mm had zonulopathy. Multivariate logistic regression showed that the ACD difference in both eyes (P=0.025) and the diagnosis of ACG (AACG vs. cataract, P<0.001; CACG vs. cataract, P=0.023) were independent risk factors associated with zonulopathy. Conclusions: The proportion of underdiagnosed zonulopathy among ACG patients is high. Better preoperative diagnostic methods for zonulopathy are needed. Zonulopathy is common in ACG patients, especially in AACG patients, suggesting that zonulopathy may be related to the pathogenesis of ACG. The shallower the ACD, the riskier the zonulopathy. ACD differences between two eyes and ACG types (including AACG and CACG) were related risk factors of zonulopathy.(This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on March 11, 2022).

[The efficacy of eltrombopag plus cyclosporine A in patients with transfusion-dependent non-severe aplastic anemia: a retrospective study from single center].

The main purpose of our study was to evaluate the efficacy and safety of eltrombopag plus cyclosporine A (CsA) in transfusion-dependent non-severe aplastic anemia(TD-NSAA). The clinical characteristics of 13 TD-NSAA patients who received initial treatment of eltrombopag plus CsA from 2019 to 2021 were retrospectively analyzed. The 3-month overall hematological response (OR) rate was 12/13. Until the end of follow-up, 12 patients responded, among whom 2 patients reached complete response (CR) and 9 patients reached partial response (PR) and 1 with HR. Paroxysmal nocturnal hemoglobinuria (PNH) developed in one patient at 6 months after treatment. Five of thirteen patients reported mild adverse reactions, which were all manageable. Compared with historical data, the combination of eltrombopag with CsA is an effective regimen in patients with TD-NSAA.

[The expressional characteristics and diagnostic values of TRBC1 in mature T-cell lymphoma].

Objective: To investigate the expression characteristics of TRBC1 protein in mature T-cell lymphoma (TCL) , and compare with T-cell receptor (TCR) -Vß repertoire analysis and TCR gene rearrangement results, to explore the value of TRBC1 in the diagnosis of TCL. Methods: The expression of TRBC1 was detected by multi-parameter flow cytometry in 30 cases of TCL, 40 cases of normal controls and 50 cases of patients without T lymphocyte proliferative diseases (non-TCL) admitted to the Department of Hematology, The First Affiliated Hospital of Nanjing Medical University. The diagnostic value of TCRVß repertoire analysis, TCR gene rearrangement and TRBC1 restricted expression detection in TCL was evaluated. Results: The positive rates of CD4(+)T and CD8(+)T cell subsets TRBC1 in normal control group were (39.6±6.5) % and (39.3±4.4) %. The positive rates of CD4(+)T and CD8(+)T cell subsets TRBC1 in non-TCL were (39.1±3.8) % and (36.0±8.4) %. All 30 cases of TCL were CD3(+)TCRγδ(-), and the positive rate of TRBC1 was >92.3% or <12.7%. All cases showed restrictive expression pattern (monoclonal expression) , which was significantly different from those of the normal control and the non-TCL cases (P<0.001) . In terms of the diagnostic performance of T cell clonality, the sensitivity of TRBC1 was 100%, the positive detection rate of TCR gene rearrangement was 92.8%, and the sensitivity of TCRVß detection was 94.1%. Kappa test showed high consistency among the three detective methods. Conclusion: Multi-parameter flow cytometry detection of TRBC1 expression level can quickly and efficiently diagnose mature T-cell lymphoma, which has good clinical application value.

[Clinical analysis of 20 cases of small B lymphocyte proliferative disease with t (14;19) (q32;q13)].

Objective: The clinical characteristics and prognosis of 20 patients with small B-lymphocyte proliferative disease with t (14;19) (q32; q13) were analyzed to improve the understanding of such rare cases. Methods: The clinical data of 20 patients with t (14; 19) (q32; q13) small B lymphocyte proliferative disease treated in the First Affiliated Hospital of Nanjing Medical University from April 2013 to December 2020 were retrospectively collected and analyzed. Among them, 10 cases were chronic lymphocytic leukemia (CLL) and 10 cases were other small B-cell malignancies. Results: Among the 20 cases, 10 were male and 10 were female, and the median age at diagnosis was 53.5 (35-88) years old. All patients had absolute lymphocytosis, 19 patients had lymphadenopathy, and 10 patients had splenomegaly. With a median follow-up of 36 (4-163) months, three patients died, and 11 patients had a time to treatment (TTT) ≤12 months. Ten patients (50%) were accompanied by +12, two patients (2/17, 12%) were accompanied by 13q-. Moreover, we found that t (14;19) was associated with unmutated immunoglobulin heavy-chain variable (IGHV) somatic mutation (17/19, 89%) and a biased use of IGHV4-39 (7/17, 41%) was observed. Next-generation sequencing detected one or more gene mutations in 14 (14/17, 82%) cases and a total of 25 gene mutations had been revealed, of which the most frequent were NOTCH1 (35%) , followed by SF3B1 (24%) and KMT2D (18%) . For 10 CLL patients, five (50%) were defined as Rai Ⅲ/Binet C. It is noteworthy that among the 20 cases, two cases actually involved Richter transformation. Conclusions: Small B-cell malignant tumors with abnormal t (14; 19) show unique clinical biological characteristics, often accompanied by a variety of adverse prognostic factors, and tend to have an aggressive clinical course.

[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.

[Comparative analysis of high risk factors between early-onset pre-eclampsia and late-onset pre-eclampsia].

Objective: To explore the difference of high-risk factors between early-onset and late-onset pre-eclampsia, and to further understand high-risk factors of pre-eclampsia. Methods: Clinical data of pre-eclampsia pregnant women in 160 medical institutions in China in 2018 were retrospectively analyzed, including 8 031 cases of early-onset pre-eclampsia and 12 969 cases of late-onset pre-eclampsia. The proportion of high-risk factors, different body mass index (BMI) and age stratification between early-onset group and late-onset group were compared. Results: (1) Univariate analysis of high-risk factors: the proportions of high-risk factors in early-onset group and late-onset group were compared, and the differences were statistically significant (all P<0.05). Among them, the proportions of primipara and multiple pregnancy in early-onset group were lower than those in late-onset group, while the proportions of pregnant women with advanced age, irregular antenatal examination, obesity, family history of hypertension, pre-eclampsia, diabetes, kidney diseases, immune system diseases and assisted reproductive technology were higher than those in late-onset group. (2) Hierarchical analysis of BMI: the proportion of pregnant women with BMI≥24 kg/m2 in early-onset group [48.2% (2 828/5 872) vs 45.5% (4 177/9 181), respectively; P=0.001] and the proportion of pregnant women with BMI ≥28 kg/m2 in early-onset group [19.5% (1 143/5 872) vs 18.0% (1 656/9 181), respectively; P=0.028] were significantly higher than those in late-onset group. (3) Age stratification analysis: the proportion of pregnant women aged 35-39 years in the early-onset group [21.8% (1 748/8 023) vs 17.5% (2 110/12 068), respectively; P<0.01], the proportion of pregnant women 40-44 years old [6.8% (544/8 023) vs 5.4% (648/12 068), respectively; P<0.01], and the proportion of pregnant women ≥45 years old [0.7% (58/8 023) vs 0.5% (57/12 068), respectively; P=0.021] were significantly higher than those in the late-onset group. (4) Multivariate analysis: advanced age (≥35 years old), multiple pregnancy, irregular antenatal examination or transfer from other hospitals, family history of hypertension (including paternal, maternal and parental lines), previous history of pre-eclampsia, kidney diseases, immune system diseases (systemic lupus erythematosus, antiphospholipid antibody syndrome) and assisted reproductive technology pregnancy were the risk factors affecting the severity of pre-eclampsia (all P<0.05). Conclusion: Pregnant women with high risk factors such as age ≥35 years old, BMI ≥24 kg/m2 before pregnancy, family history of hypertension, history of pre-eclampsia, chronic kidney diseases, immune diseases (mainly including systemic lupus erythematosus and antiphospholipid syndrome) and assisted reproductive technology are more likely to have early-onset pre-eclampsia.

[Clinical characteristics of T-cell large granular lymphoblastic leukemia with STAT3 gene mutation].

Objective: This study aims to explore the clinical characteristics of T-cell large granular lymphocyte leukemia (T-LGLL) patients with STAT3 mutation status and provide a reference for clinical management of such patients. Methods: The clinical data of T-LGLL patients between 2009 and 2019 in Jiangsu Province Hospital were retrospectively analyzed. Differences in baseline clinical data, treatment responses, and survival outcomes in patients with STAT3 mutations or with no mutations were compared. Results: A total of 80 patients were included, including 66 patients without STAT3 mutation and 14 patients (17.5%) with STAT3 mutation. The frequency of Y640F mutation was the highest (42.9%) . Compared with non STAT3 mutation group, STAT3 mutation group had lower HGB (67.5 g/L vs 82.5 g/L, P=0.018) , lower neutrophil count (0.665×10(9)/L vs 1.465×10(9)/L, P<0.001) , higher LDH (229 U/L vs 198 U/L, P=0.041) , higher ferritin (402.5 g/L vs 236.0 g/L, P=0.029) , higher expression rate of TCR Vß subfamily (89.2% vs 65.4%, P=0.014) and higher proportion of patients with treatment indications (100% vs 74%, P=0.033) . The complete remission rates of STAT3 mutation group and non mutation group were 38.5% and 32.7%, respectively, with no significant difference (P=0.748) . The overall response rate of first-line immunosuppressive therapy in STAT3 mutation group and non mutation group were 69.2% and 69.4%, respectively, with no significant difference (P=1.000) . The median follow-up time was 63 (2-121) months. There was no significant difference in the overall survival time between the two groups (P=0.170) . Conclusions: T-LGLL patients with STAT3 mutations seems to be correlated with an increased tumor burden and high treatment demand, and had a good response to first-line immunotherapies. The prognostic significance of STAT3 mutation in T-LGLL patients requires further validation.

Genome-wide DNA methylation and transcription analysis in tongue and biceps femoris muscles of cloned pigs with macroglossia.

Cloned animals are prone to abnormal phenotypes such as enlarged tongue, fetal oversize, and progeria. In the present study, whole-genome bisulfite sequencing and mRNA sequencing were performed on tongue and biceps femoris muscles of cloned piglets with and without macroglossia, in an attempt to elucidate the epigenetic causes of the macroglossia phenotype. We identified 14 958 and 18 752 differentially methylated regions in the tongue and biceps femoris muscles, respectively, of macroglossia piglets and these correspond to 4574 and 4772 differentially methylated genes compared with the control group (piglets without macroglossia). Larger methylation difference was found in tongue muscle than in biceps femoris muscle. In total, 114 genes in tongue and 72 genes in biceps femoris muscles were found to be differentially expressed between the two groups. Of these differentially expressed genes in tongue muscle, 31 were also differentially methylated genes, among which DIO3 and ZIC1 were imprinting or predicted imprinting genes. These two and another six overlapping genes (ALDH1A2, MKX, MAB21L2, CA3, RANBP3L, and MYL10) are crucial factors involved in embryonic development or tissue and organ development. GO enrichment analysis suggested possible alteration of these processes. Our study provides novel molecular insights into the formation of macroglossia in cloned pigs.