[MiR-132-3p negatively regulates CAMTA1 to promote Schwann cell proliferation and migration and alleviates I-125 seeds-induced exacerbation of facial nerve injury in rats].

OBJECTIVE: To investigate the regulatory effect of miR-132-3p on calmodulin-binding transcription activator 1 (CAMTA1) and Schwann cell activity in rats with facial nerve injury (FNI) treated with I-125 seeds. METHODS: Rat Schwann cells were irradiated with I-125 seeds and transfected with miR-132-3p mimic, miR-132-3p inhibitor or sh-CAMTA1. The expressions of S100B and ß-tubulin Ⅲ in the cells were detected with immunofluorescence assay, and the expressions of miR-132-3p and CAMTA1 protein were determined using RT-qPCR and Western blotting, respectively. EdU staining and Transwell assay were used to evaluate the changes in cell proliferation and migration ability. In a rat model of FNI, I-125 seeds were implanted into the facial tissues near the facial nerve 2 weeks before modeling, and miR-132-3p mimic was injected subcutaneously in the face after modeling. The pathologies of the facial nerve was assessed by HE, LFB and immunofluorescence staining. The targeting relationship between miR-132-3p and CAMTA1 was verified using StarBase v2.0 database and dual-luciferase reporter assay. RESULTS: Rat Schwann cells showed high expressions of S100B and ß-tubulin Ⅲ. I-125 seeds radiation significantly decreased miR-132-3p expression and repressed proliferation and migration of the cells (P < 0.001). Overexpression of miR-132-3p or CAMTA1 knockdown obviously enhanced proliferation and migration of the Schwann cells, while miR-132-3p knockdown produced the opposite effect. MiR-132-3p negatively regulated CAMTA1 expression. In the rat models of FNI, miR-132-3p injection significantly inhibited CAMTA1 expression and attenuated I-125 seeds-induced exacerbation of FNI. CONCLUSION: Overexpression of miR-132-3p suppresses CAMTA1 expression and promotes Schwann cell proliferation and migration to alleviate I-125 seeds-induced exacerbation of FNI in rats.

[Correlation analysis between Pirani score and talo-navicular angle,calcaneo-cuboid angle and tibio-calcaneall angle of infant clubfoot under ultrasound].

Objective: To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods. Methods: This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was (M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results: The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up (F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score (r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score (r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score (r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion: Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

AI's deep dive into complex pediatric inguinal hernia issues: a challenge to traditional guidelines?

OBJECTIVE: This study utilized ChatGPT, an artificial intelligence program based on large language models, to explore controversial issues in pediatric inguinal hernia surgery and compare its responses with the guidelines of the European Association of Pediatric Surgeons (EUPSA). METHODS: Six contentious issues raised by EUPSA were submitted to ChatGPT 4.0 for analysis, for which two independent responses were generated for each issue. These generated answers were subsequently compared with systematic reviews and guidelines. To ensure content accuracy and reliability, a content analysis was conducted, and expert evaluations were solicited for validation. Content analysis evaluated the consistency or discrepancy between ChatGPT 4.0's responses and the guidelines. An expert scoring method assess the quality, reliability, and applicability of responses. The TF-IDF model tested the stability and consistency of the two responses. RESULTS: The responses generated by ChatGPT 4.0 were mostly consistent with the guidelines. However, some differences and contradictions were noted. The average quality score was 3.33, reliability score was 2.75, and applicability score was 3.46 (out of 5). The average similarity between the two responses was 0.72 (out of 1), Content analysis and expert ratings yielded consistent conclusions, enhancing the credibility of our research. CONCLUSION: ChatGPT can provide valuable responses to clinical questions, but it has limitations and requires further improvement. It is recommended to combine ChatGPT with other reliable data sources to improve clinical practice and decision-making.

[Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells].

Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.

Clinical significance of extrathyroidal extension to major vessels in papillary thyroid carcinoma.

PURPOSE: Gross extrathyroidal extension (gETE) into major vessel is considered the most advanced stage of the locally advanced papillary thyroid cancer (PTC). Surgical intervention may not benefit some patients at this disease stage or even result in intraoperative death due to massive hemorrhage; however, it is still considered an effective strategy for most cases. The lack of description for this challenging invasion in PTC warrants detailed characterization of its pattern, risk factors, optimal surgical method, and prognostic value. METHODS: In total, 3127 patients diagnosed as having PTC were enrolled and categorized into two the following groups, namely the major vessel invasion (MVI) group (n = 30) and the control group (n = 3097). Data regarding clinicopathological and demographic characteristics, vascular invasion sites, postoperative complications, locoregional recurrence, distant metastasis, and surgical strategies were collected. Predictive disease-free survival (DFS) was also compared between the two groups. RESULTS: MVI was independently associated with invasion of the esophageal extension, age < 55 years, tumor size > 1 cm, lateral lymph node metastasis, and distant metastasis (P = 0.00; P = 0.01; 0.05; P = 0.00; P = 0.00, respectively). The difference in the predictive DFS between the two groups was significant (P = 0.00), and the difference remained significant even in patients with ETE when compared with patients without ETE (P = 0.00). Additionally, predictive DFS did not differ significantly between patients who received vessel repairment and those who received vessel resection (P = 0.28). CONCLUSIONS: This study first characterized the gross MVI pattern exhibited by PTC and the risk factors for MVI. Additionally, it demonstrated the DFS of patients with PTC. Extensive gross MVI significantly worsened the biological characteristics of PTC. Regardless of the high risk and difficulty of the operation, patients still benefited from the surgical intervention, and vessel repairment may be the optimal surgical strategy.

[Early loss of primary molar and permanent tooth germ caused by the use of devitalizer during primary molar root canal therapy: Two cases report].

Devitalization has been widely used in the root canal therapy of primary and permanent teeth in China more than ten years ago. With the development of local anesthetic drugs and injection technologies, this treatment method with high potential risks has been gradually abandoned. However, a questionnaire survey targeted all the participants at the 2018 China Pediatric Dentistry Conference showed that the devitalizer utilization proportion was still as high as 38.1% (383/1 005), even though the ratio was much lower than 75.5% (105/139) in 2003. These doctors had pay more attention to tissue burn caused by devitalizer marginal leakage or direct leakage, and know how to identify and handle with devitalizer burn. Devitalizers were usually made of arsenic trioxide, metal arsenic or paraformaldehyde, which have cytotoxicity, allergenicity, mutagenicity, carcinogenicity, and teratogenic effects on animals. Marginal leakage of devitalizers have high risks of causing soft and hard tissue necrosis. Most of the dentists have an understanding of the potential damages of arsenic containing devitalizers, so they will choose parafor maldehyde with relatively less toxicity. Paraformaldehyde has a certain self limitation, and there are few cases reported, so some dentists lack of vigilance. Paraformaldehyde can also causes tissue necrosis if leakage happens, and the treatment methods are similar to that of arsenic containing devitalizers. When handling with devitalizers burn, the necrosed soft and hard tissue, for example gingiva, alveolar bone or teeth that cannot keep, must be completely removed until fresh blood appears, then rinse with large amount of saline and seal with iodoform gauze. This paper described two cases of devitalizer burn during the root canal treatment of primary molars, both of the doctors failed to identify the devitalizer burn symptoms in the early stage, thus didn't do proper treatments immediately after burning. Resulting in the necrosis of large area of gingiva and alveolar bone, loss of primary molars and permanent tooth germs 1-2 months after devitalizer burn. This paper reported these two cases in detail in order to warn dentists the high risks of using any kind of devitalizers, help them learn how to identify and treat devitalizer burn, and remind them to stop using devitalizers as soon as possible.

[Prospective study of the caries recurrence risks after severe early childhood caries treatments under general anesthesia].

Objective: To study prospectively the caries characteristics of the children who suffered severe early childhood caries (S-ECC) and received dental caries treatment under general anesthesia and to explore the related risk factors of caries recurrence after treatment. Methods: During December 2012 to August 2014, eighty-three children aged 2-4 years with S-ECC who underwent one caries treatment session under general anesthesia in Peking University School and Hospital of Stomatology participated in this study. Data of demographics, clinical characteristics, dietary and oral hygiene habits of the participants were collected before the treatment and 1-, 7- and 13-months after the treatment. All data were then analyzed to find out whether the factors were related to caries relapse. Results: Among the 70 children who completed 7-13 months follow-up, twenty-nine children (41%) remained caries-free and 41 children (59%) had a few caries recurrence during the observation period. All the teeth suffered different variation of caries recurrence except mandibular deciduous incisors. As for the types of caries recurrence after caries treatment under general anesthesia, the maxillary deciduous incisors usually showed secondary caries (new caries/secondary caries numbers were 1/12), the canines and first deciduous molars occurred both secondary and new caries (new caries/secondary caries numbers in canines were 12/6, in first deciduous molars were 16/12) and the second deciduous molars usually presented new caries (new caries/secondary caries numbers were 19/5). After treatment, the prone tooth surfaces of caries recurrence from high to low were: adjacent surfaces of deciduous molars (37 surfaces), occlusal surface of deciduous molars (28 surfaces), adjacent surfaces of deciduous canines (13 surfaces), buccal and lingual surfaces of deciduous molars (12 surfaces), labial and lingual surfaces of deciduous incisors (10 surfaces), labial and lingual surfaces of deciduous canines (8 surfaces) and adjacent surfaces of deciduous incisors (5 surfaces). There were no significant differences in the children's demographics and clinical characteristics between relapse and non-relapse groups (P>0.05). Patients in the relapse group had higher sugar intake frequencies than those in the non-relapse group at both 7- and 13-month follow-ups (P<0.05). Conclusions: Children of 2-4 years old with S-ECC have a high risk of caries recurrence after caries treatment under general anesthesia and need to recieve regular oral examination. During the follow-ups, the prevention and treatment of new and secondary caries of deciduous molars and secondary caries of deciduous incisors should be focused on. High frequency of sugar intake is an important risk factor of recurrent caries for children with S-ECC after caries treatment.

[Expression profile of intervertebral disc degeneration-specific genes: a transcriptome sequencing-based analysis].

OBJECTIVE: To identify new therapeutic targets for intervertebral disc degeneration (IDD) by analyzing gene variations in IDD. OBJECTIVE: We analyzed surgical samples of intervertebral disc from 4 patients with IDD and 3 patients with non-IDD using RNA sequencing (RNA-seq) technology to identify significant differentially expressed genes (DEGs) in IDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for gene enrichment studies to acquire the key genes and signal pathways during IDD progression. The differential expressions of the identified genes in IDD were validated in clinical samples with qRT-PCR. OBJECTIVE: The transcriptome profile revealed 512 significant DEGs, which were enriched in terms of keratinization, extracellular matrix (ECM) components, growth factor binding, and inflammatory chemotaxis in GO analysis. The top 10 terms of KEGG enrichment included amoebiasis, viral protein interaction with cytokine and cytokine receptor, ECM-receptor interaction, IL-17 signaling pathway, cytokine-cytokine receptor interaction, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, chemokine signaling pathway and estrogen signaling pathway. Thirteen DEGs selected as the targets for qRT-PCR validation showed significant differential expressions in IDD (P < 0.001), and their expression trends were all consistent with the results of RNA-seq. Among these genes, 10 genes showed significant intergroup fold change (Log2FoldChange>1). OBJECTIVE: ECM, growth factors, collagen components, inflammatory chemokines and such signal pathways as TNF-α and PI3K-Akt all have important contributions to IDD progression and may thus serve as new therapeutic targets for treatment of IDD.

[Analysis of correlation factors of contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma with lateral cervical lymph node metastasis].

Objective: To examine the correlation factors of contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma with lateral cervical lymph node metastasis. Methods: The clinical data of patients with unilateral papillary thyroid carcinoma who underwent total thyroidectomy and bilateral central lymph node dissection and ipsilateral cervical lymph node dissection from June 2016 to June 2018 at Department of Thyroid Surgery, West China Hospital, Sichuan University were analyzed retrospectively. A total of 317 patients, including 87 males and 230 females, aged (41.4±12.1) years (range: 16 to 75 years), were enrolled in this study. The risk factors of contralateral central lymph node metastasis were analyzed by χ2 test and Spearman correlation analysis. Results: There were 116, 69, 269, and 181 cases of pretracheal lymph node, prelaryngeal lymph node, ipsilateral central lymph node and contralateral central lymph node metastasis, respectively, and 16 cases of skipping metastasis. Univariate analysis showed that contralateral central lymph node metastasis was associated with gender, maximum tumor diameter, capsule invasion, pretracheal lymph node metastasis, prelaryngeal lymph node metastasis, and ipsilateral central lymph node metastasis (all P<0.05). Spearman correlation analysis showed that male (rs=0.162, P=0.004), maximum tumor diameter>10 mm (rs=0.184, P=0.001), capsule invasion (rs=0.135, P=0.016), pretracheal lymph node metastasis (rs=0.394, P<0.01), prelaryngeal lymph node metastasis (rs=0.272, P<0.01) and ipsilateral central lymph node metastasis (rs=0.203, P<0.01) were independent correlation factors for contralateral central lymph node metastasis. Conclusion: For patients with unilateral papillary thyroid carcinoma with ipsilateral cervical lymph node metastasis, bilateral central lymph node dissection should be considered if male, tumor diameter>10 mm, capsule invasion, pretracheal lymph node metastasis, prelaryngeal lymph node metastasis, or ipsilateral central lymph node metastasis.

[Analysis of the efficacy of the Ponseti method for treatment of secondary clubfoot in young children with tethered cord syndrome].

Objective: To explore the feasibility of Ponseti method in treatment of secondary clubfoot in young children with Tethered Cord Syndrome(TCS). Methods: The clinical data of 53 young children with clubfeet treated with Ponseti method from March 2014 to March 2017 at Department of Pediatric Orthopedics, the Third Affiliated Hospital of Zhengzhou University were analyzed retrospectively. These patients were divided into TCS group and Idiopathic group according to the etiology. There were 19 patients (33 feet) in TCS group,with an mean age of 2.8 months(range:0.2 to 24.0 months), including 13 males and 6 females, 5 patients with unilateral clubfeet and 14 patients with bilateral clubfeet. There were 34 patients (45 feet) in idiopathic group, with an mean age of 3.1 months(range: 0.1 to 21.0 months), including 18 males and 16 females, 23 patients with unilateral clubfeet and 11 patients with bilateral clubfeet. All the children received casts correction according to Ponseti method, and were followed up at 3 weeks, 3 months, 6 months and every 6 months after the Achilles tendon tenotomy or the last cast correction. Complications were recorded and therapeutic effect was evaluated of these children by Dimeglio Scoring System and the International Clubfoot Study Group (ICFSG) at the last follow-up. Independent t test, Mann-Witney U test or χ(2) test were used to compare the indicators of the two groups. Results: The number of plaster fixation in TCS group was (6.1±2.0) times, and that of idiopathic group was (4.8±1.0) times(t=3.482, P<0.01).In TCS group, 22 feet treated with Achilles tendon transection and that of idiopathic group was 40 feet(χ(2)=0.279, P=0.598). There were 18 cases recurrence in TCS group and 8 cases in Idiopathic group (t=11.149, P<0.01). In TCS group, 16 cases (27 feet) completed the initial correction, the success rate was 60.6% (27/33), 3 cases (6 feet) could not correct the deformity after 9 to 10 times of plaster fixation, and then underwent soft tissue release.In idiopathic group, 34 cases (45 feet) achieved initial correction after Ponseti treatment(χ(2)=6.488, P=0.011).At the last follow up, there were 5 cases (9 feet) in TCS group and 2 cases (2 feet) in idiopathic group underwent soft tissue release(χ(2)=6.110, P=0.013). The classification grade of ICFSG score of the two groups without soft tissue release were (2.1±0.6) and (1.8±0.7), the difference was not statistically significant (t=1.765, P=0.082). All the children had no skin ulceration, bedsores, skin allergy and other complications. Conclusion: Ponseti method is effective in the treatment of clubfoot secondary to TCS, and the functional recovery is similar to that of children with idiopathic clubfoot.

[Alveolar capillary dysplasia with misalignment of the pulmonary veins: a case report and literature review].

Objective: To investigate the clinical, pathological and genetic characteristics of neonatal alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV). Methods: The clinical manifestations, radiographic examinations, pathology and parental genetic analysis of a newborn with FOXF1 variation induced ACDMPV, who was hospitalized in the Department of Neonatology of Shenzhen Children's Hospital in January 2020, were extracted and analyzed. Related literature up to March 2020 with the key words of "Alveolar capillaries dysplasia" "Alveolar capillary dysplasia with misalignment of the pulmonary veins" "FOXF1" in PubMed, CNKI, Wanfang, CQVIP database and Leiden Open Variation database (LOVD) were searched. Results: A full-term male newborn （1 hour of age） was admitted due to anal atresia. Surgical repair of anal atresia and omphalocele was performed on the first day of life, and gallbladder absence and Meckel's diverticulum were identified during the operation. Respiratory distress with hypoxemia developed at about 6 hours of life, and persistent pulmonary hypertension developed and progressed after surgery, with poor response to mechanical ventilation and pulmonary vasodilators. This infant passed away at 26 days of life. Lung biopsy showed decreased alveolar units and thickened interalveolar septa, reduced alveolar capillary density and thickened walls of peripheral pulmonary arteries, and misaligned pulmonary veins adjacent to the pulmonary arterioles, which were consistent with ACDMPV. The whole exome sequencing revealed a heterozygous novel frameshift of FOXF1 gene located in chromosome 16q24.1 c376_377insT; p.(Pro126fs). According to the bioinformatics analysis, this variation was likely to be pathogenic as it was associated with coding disorder of FOXF1 Pro126, resulting in truncation of the encoded protein. This novel variation had not been reported in the human gene mutation database (HGMD), ESP6500siv2_ALL, 1000g2015aug_ALL or dbSNP147 database. Previous 6 literatures reported 54 variants, including 28 missense, 10 nonsense, 11 frameshift, 2 deletion, 1 synonymous, and 2 extensions. Only three of the reported 45 cases （24 males, 21 females） were still alive as of the time of this study. Conclusions: Typically, ACDMPV is a catastrophic disease in neonatal period with high mortality. Lung biopsy and genetic testing should be considered in infants who present with persistent pulmonary hypertension and refractory hypoxemia, especially when combined with extrapulmonary abnormalities.

Organoid of ovarian cancer: genomic analysis and drug screening.

Ovarian cancer is the most common malignant tumors of the female reproductive system, and its standard treatments are cytoreductive surgery and platinum-based adjuvant chemotherapy. Great advances have been achieved in novel treatment strategies, including targeted therapy and immunotherapy. However, ovarian cancer has the highest mortality rate among gynecological tumors due to therapeutic resistance and the gap between preclinical data and actual clinical efficacy. Organoids are a 3D culture model that markedly affects gene analysis, drug screening, and drug sensitivity determination of tumors, especially when used in targeted therapy and immunotherapy. In addition, organoid can lead to advances in the preclinical research of ovarian cancer due to its convenient cultivation, good genetic stability, and high homology with primary tumors.

Reconstruction of mandibular defects using vascularized fibular osteomyocutaneous flap combined with nonvascularized fibular flap.

BACKGROUND: The height of single-layer fibular flap is not long enough to return to the ideal height of the mandible. While the double-layer vascularized fibular osteomyocutaneous flap(VFF) is more complicated in shaping and fixation, along with a longer operation time. The aim of this study was to investigate the clinical effect of VFF combined with nonvascularized fibular flap(NVFF) in the reconstruction of mandibular defect. MATERIAL AND METHODS: From September 2016 to June 2018, 15 patients with benign mandibular tumors underwent reconstruction with VFF and NVFF. SimPlant Pro ™ software (version 11.04) was used to simulate reconstruction of the mandible preoperatively. RESULTS: All patients were followed up for 8-23 month, with an average of 11.7 months. 15 VFFs survived well. Among the 15 NVFFs, one was almost completely absorbed, two with partial absorption, and the remaining survived regardless of the small amount of absorption. The postoperative absorption of the whole fibula was 7.53±6.362%, a favorable facial contour and speech function were attained. CONCLUSIONS: The VFF combined with NVFF to reconstruct the mandibular defect can restore the vertical height of the mandible and achieve satisfactory clinical results.

[Evaluation of different staging systems and prognostic analysis of 110 primary gastrointestinal diffuse large B cell lymphoma].

Objective: To compare the prognostic efficiency of Lugano staging, TNM staging and Musshoff staging systems in patients with primary gastrointestinal diffuse large B-cell lymphoma(PGI-DLBCL) and investigate its clinical features and prognosis. Methods: The clinical data of 110 patients with PGI-DLBCL in Tianjin Medical University Cancer Institute and Hospital from May 2008 to August 2017 was retrospectively analyzed. The stage of lymphoma was assessed following Lugano staging, TNM staging and Musshoff staging systems respectively. The prognostic value was compared mainly according to the situation of 5-year overall survival (OS)and the influence of different clinical features on prognosis of patients was also investigated. Results: The median age of the whole study was 55(range 17-92) years old. With a median follow-up time of 36 (range 1-115) months, the median progression-free survival (PFS) was 35 (range 0-86) months, and the median overall survival was 37 (range 2-104) months. The 5-year OS rate of Lugano stagingⅠ, Ⅱ, Ⅲ and Ⅳ were 77.6%, 73.4%, 69.7%, 12.2% (χ(2)=63.395, P<0.001) respectively. The 5-year OS rate of TNM staging Ⅰ, Ⅱ, Ⅲ and Ⅳ were 77.6%, 75.9%, 25.0%, 9.3% (χ(2)=65.802, P<0.001) respectively. The 5-year OS rate of Musshoff stagingⅠ, Ⅱ, Ⅲ and Ⅳ were 84.5%, 68.4%, 25.0%, 9.3% (χ(2)=66.966, P<0.001) respectively. By Cox multiple-factors analysis, Lugano staging system was the only independent prognosis risk factor for PFS (HR=4.987, 95%CI: 1.421-17.498, P=0.009) and OS (HR=5.659, 95%CI: 1.563-20.485, P=0.008) of PGI-DLBCL. Univariated analysis revealed that the factors affecting PFS and OS of patients with PG-DLBCL include B-symptom, Eastern Cooperative Oncology Group performance status (ECOG PS), the number of extranodal lesions, serum lactate dehydrogenase (LDH), International prognostic index (IPI) score, staging and therapeutic regimen(all P values of PFS and OS<0.05). Patients with PG-DLBCL who received chemotherapy alone showed a better survival than others (PFS P=0.004; OS P<0.001); the factors affecting PFS and OS of patients with PI-DLBCL include ß2-microglobulin(ß2-MG), serum albumin(ALB) levels, LDH and staging (all P values of PFS and OS<0.05). Therapeutic regimen didn't affect those patients' survival (PFS P=0.661, OS P=0.720). The additional use of Rituximab failed to improve the survival of patients with PG-DLBCL and PI-DLBCL respectively (all P values of PFS and OS>0.05). Conclusions: Compared with TNM staging and Musshoff staging systems, Lugano staging system provides the best prognostic value in PFS and OS for patients with PGI-DLBCL. Accompany with B-sympto, higher ECOG PS score, more extranodal lesions, increased LDH, higher IPI score and later period are negative factors for PG-DLBCL. Increased ß2-MG and LDH, lower ALB level and later period are negative factors of PI-DLBCL.

[A comparative study of induction chemotherapy with or without autologous hematopoietic stem cell transplantation in the treatment of newly diagnosed young medium/high risk diffuse large B cell lymphoma patients].

Objective: To compare the efficacy of induction chemotherapy with or without autologous hematopoietic stem cell transplantation (auto-HSCT) for newly diagnosed young diffuse large B cell lymphoma (DLBCL) patients. Methods: The retrospective study was performed in 90 cases of young patients (≤60 years) with newly diagnosed DLBCL and an age-adjusted International Prognostic Index (aa-IPI) score of 2 or 3. All of them were treated with R-CHOP (32 cases, rituximab combined with CHOP), dose-intensive regimens (DA-EPOCH, Hyper CVAD/MA or ESHAP) combined with or without rituximab (25 cases), and consolidated with up-front auto-HSCT (33 cases), respectively. The efficacy and the potential predictors were evaluated. Results: ①The median age of 90 patients was 43 (18-60) years old. The median follow-up time was 42 (3-110) months. ②The 5-year progression-free survival (PFS) for R-CHOP group, dose-intensive chemotherapy group and auto-HSCT group were (33.5±10.7) %, (55.3±10.1) % and (65.8±13.6) % (P=0.012), the 5-year overall survival (OS) were (49.7±9.0) %, (61.6±10.2) % and (78.6±7.8) % (P=0.035), respectively. There was no significant difference in 5-years PFS and OS between the R-CHOP group and dose-intensive chemotherapy group (P=0.519, P=0.437) compared with that of the dose-intensive chemotherapy group, auto-HSCT group has higher 5-year PFS (P=0.042). ③ When stratified with IPI score, the high-risk group treated with auto-HSCT (26 cases) showed similar 5-years PFS and 5-years OS to those in the low-risk group with chemotherapy alone (12 cases were in R-CHOP group and 8 cases were in dose-intensive chemotherapy group) [5-years PFS were (62.3 ±14.3)%, (58.3 ±18.6)% and (51.4±18.7)%, respectively, P=0.686; 5-years OS were (69.2±13.9)%, (62.5±15.5)% and (58.3±18.6)%, respectively, P=0.592]. ④However, the high-risk group treated with auto-HSCT (26 cases) showed superior 5-years PFS (P=0.002) and 5-years OS (P=0.019) compared to the high-risk group with chemotherapy alone (20 cases were in R-CHOP group and 17 cases were in dose-intensive chemotherapy group) [5-years PFS were (62.3±14.3)%, (41.1±13.5)% and (21.9±11.6)%, respectively; 5-years OS were (69.2±13.9)%, (51.5%±14.0)% and (35.4±13.6)%, respectively]. ⑤In the univariate analysis, as a whole, patients diagnosed with GCB subtype had higher 3-years PFS (P=0.022) and 3-years OS (P=0.037) compared to non-GCB subtype patients; in subgroup analysis, patients diagnosed with GCB subtype had higher 3-years PFS and 3-years OS compared to non-GCB subtype both in R-CHOP group (P=0.030, P=0.041) and dose-intensive chemotherapy group (P=0.044, P=0.047), but not in auto-HSCT group (P=0.199, P=0.093). ⑥In the multivariate analysis, different molecular classification (GCB/non-GCB) was an independent predictor for PFS and OS both in R-CHOP group [HR=0.274 (95% CI 0.094-0.800), P=0.018; HR=0.408 (95% CI 0.164-1.015), P=0.045] and dose-intensive chemotherapy group [HR=0.423 (95% CI 0.043-1.152), P=0.048; HR=5.758 (95% CI 0.882-6.592), P=0.035]. However, there was no significant difference in PFS and OS for auto-HSCT group between GCB/non-GCB patients. Conclusion: Induction chemotherapy followed by up-front auto-HSCT has significant effect on efficacy for young and untreated patients with high risk DLBCL. Combined with induction chemotherapy followed by up-front auto-HSCT could improve the prognosis of non-GCB patients.

[Prognostic value of (18)F-FDG PET/CT in newly diagnosed multiple myeloma patients].

Objective: To assess the prognostic value of (18)F-FDG PET/CT and its relationship with clinical features in newly diagnosed MM patients. Methods: A total of 123 patients with newly diagnosed MM in Tianjin Medical University Cancer Institute and Hospital from September 2008 to December 2017 were retrospectively reviewed. The overall survival (OS) and progression free survival (PFS) were estimated by Kaplan-Meier analysis and the distribution of OS and PFS were compared using log-rank test. Cox regression was used to identify the independent prognostic factors. Results: Of all 123 patients, there were 43 patients (35.0%) who had extramedullary diseases (EMD). Compared to the patients without EMD, the PFS (24.5 months vs 37.8 months, P<0.05) and OS (30.1 months vs 51.4 months, P<0.05) of the patients with EMD at diagnosed was significantly inferior. In multivariate analysis, ß2-MG≥5.5 mg/L, age≥65, EMD on (18)F-FDG PET/CT and without CR at the ending of treatments were the four factors leading to poor prognosis. According to the above four factors, the patients were regrouped into low risk, medium risk and high risk groups, the significant difference existed (P<0.01) in these groups. Conclusion: (18)F-FDG PET/CT is helpful in predicting the prognosis of newly diagnosed MM patients.

[Expressions and prognostic significance of PTEN and PD-1 protein in patients with classical Hodgkin's lymphoma].

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin's lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions: This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.