Hematoporphyrine injection-based photodynamic therapy for Perianal Paget's disease: A case report.

Paget's disease of the perianal skin (PPD) is a rare form of extramammary Paget's disease, which can manifest as either a primary intraepithelial adnexal neoplasm or as a secondary condition resulting from the spread of an underlying colorectal lesion. Surgical resection is the primary treatment for PDD, but it poses risks to the aesthetic appearance and functional integrity of the anus. Moreover, its clinical application is limited, particularly in cases of lesions present in multiple skinfold areas, multiple and recurrent lesions, extensive lesion areas, or in elderly patients with poor health. Hematoporphyrin derivative photodynamic therapy (HpD-PDT) serves as an alternative treatment for patients who are not suitable candidates for surgery and for conditions characterized by extensive and discontinuous disease. Here, we present the case of a 70-year-old man with PPD, presenting perianal skin lesions extending beyond the dentate line into the anal canal. When considering HpD-PDT, it is essential to take into account the preservation of function, patient preferences, and potential adverse effects. Subsequent to HpD-PDT, the lesion was effectively eradicated, and anal function was preserved without any notable proliferative, atrophic scarring, or other side effects. Therefore, HpD-PDT proves to be an effective treatment for PPD, offering aesthetic improvement, minimal functional disruption, and a high level of tolerability.

[Clinical features and long-term prognostic analysis of relapsed pediatric acute lymphoblastic leukemia].

Objective: To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to relapse, relapse site, and molecular biological features of 217 relapsed ALL children primarily treated by the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between April 2008 and April 2015 were collected and analyzed in this retrospective cohort study. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 217 relapsed patients was 5 (3, 7) years. There were 135 males and 82 females. The time from initial diagnosis to relapse of 217 children was 22 (10, 39) months. After relapse, 136 out of 217 children (62.7%) received treatment and the follow-up time was 65 (47, 90) months. The 5-year OS rate and EFS rate of the 136 relapsed children were (37±4) % and (26±4) %, respectively. The predicted 10-year OS rate and EFS rate were (35±5) % and (20±4) %, respectively. Univariate analysis showed that the 5-year OS rate in the group of patients with late relapse (43 cases) was significantly higher than those with very early (54 cases) and early relapse (39 cases) ((72±7)% vs. (16±5)%, (28±8)%, χ2=35.91, P<0.05), 5-year OS rate of the isolated extramedullary relapse group (20 cases) was significantly higher than isolated bone marrow relapse group (102 cases) and combined relapse group (14 cases) ((69±11)% vs. (31±5)%, (29±12)%, χ2=9.14, P<0.05), 5-year OS rate of high-risk group (80 cases) was significantly lower than standard-risk group (10 cases) and intermediate-risk group (46 cases) ((20±5)% vs. (90±10)%, (54±8)%, χ2=32.88, P<0.05). ETV6::RUNX1 was the most common fusion gene (13.2%, 18/136). The predicted 10-year OS rate of relapsed children with positive ETV6::RUNX1 was significantly higher than those without ETV6::RUNX1 (118 cases) ((83±9)% vs. (26±5)%, χ2=14.04, P<0.05). The 5-year OS for those accepted hematopoietic stem cell transplantation (HSCT) after relapse (42 cases) was higher than those without HSCT (94 cases) ((56±8)% vs. (27±5)%, χ2=15.18, P<0.05). Multivariate analysis identified very early/early relapse (HR=3.91, 95%CI 1.96-7.79; HR=4.15, 95%CI 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse (HR=6.50, 95%CI 2.58-16.34; HR=5.19, 95%CI 1.78-15.16), with ETV6::RUNX1 (HR=0.23, 95%CI 0.07-0.74) and HSCT after relapse (HR=0.24, 95%CI 0.14-0.43) as independent prognostic factors for OS (all P<0.05). Conclusions: Relapsed pediatric ALL mainly occurs very early and often affects bone marrow, which confer poor outcome. ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.

[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

[Clinical features and prognostic factors of advanced myelodysplastic syndromes in children].

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 µg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

[Current situation and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023].

Objective: To explore the incidence and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023. Methods: From October 2022 to August 2023, 11 cities including Xishuangbanna in Yunnan Province, Suqian in Jiangsu Province, Chifeng and Hohhot in Inner Mongolia, Tangshan in Hebei Province, Changzhi in Shanxi Province, Yinchuan in Ningxia Province, Lanzhou and Dingxi in Gansu Province, Linyi in Shandong Province, and Tonghua in Jilin Province were selected as research sites to recruit kindergarten children and primary and secondary school adolescents in local urban areas. A total of 21 959 children and adolescents were included in this study. Demographic information, wheezing data (whether wheezing has occurred in the past and whether wheezing attacks have occurred in the past one year), personal history, family history and other information were collected through questionnaires. The multivariate logistic regression model was used to analyze the influencing factors of wheezing attacks in the past one year. Results: The mean age of 21 959 children and adolescents was (12.09±3.65) years old, and 52.3% (11 480) were boys. The incidence of wheezing history was 3.7% (816 cases), and the incidence of wheezing attacks in the past year was 2.5% (556 cases). The multivariate logistic regression model analysis results showed that compared with older age, girls, full-term natural delivery, no allergic rhinitis, no family history of allergic diseases, no passive smoking, partial diet, natural conception and childbirth, the children aged 3-18 years with young age, male, partial diet, passive smoking, family history of allergic diseases, allergic rhinitis, cesarean section, premature birth, and assisted reproduction had a higher risk of wheezing [OR (95%CI): 0.86(0.84-0.88), 1.27(1.07-1.51), 2.31(1.95-2.75), 2.09(1.76-2.47), 3.5(2.80-4.37), 4.05(3.39-4.83), 1.20(1.02-1.43), 2.26(1.66-3.09), and 1.67(1.01-2.78)]. Conclusion: From 2022 to 2023, the incidence of wheezing among children aged 3-18 years in China is not significantly higher than before, and childhood wheezing may be related to factors such as children's age, gender, dietary habits, family and personal history of allergic diseases, passive smoking, and perinatal period.

[Comparison of the effects of general anesthesia between remimazolam and propofol in pediatric patients undergoing binocular strabismus day surgery].

Objective: To compare the effects of general anesthesia between remimazolam and propofol in pediatric patients undergoing binocular strabismus day surgery. Methods: Prospectively, 60 pediatric patients, American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ, scheduled to undergo binocular strabismus daytime surgery in Beijing Tongren Hospital under general anesthesia with laryngeal mask airway from December 2021 to May 2022 were selected. They were randomly divided into Remimazolam group and Propofol group with 30 cases in each group, according to the ratio of 1∶1 by SPSS program. Patients in Remimazolam group were induced by remimazolam, remifentanil and micuronium chloride, and maintained by remimazolam and remifentanil. Patients in Propofol group were induced by propofol, remifentanil and micuronium chloride, and maintained by propofol and remifentanil. Patients in Remimazolam group were given 0.1 mg of flumazenil for antagonism 3 minutes after operation, while children in Propofol group waited for natural awakening. The primary outcome was the time from drug withdrawal to laryngeal mask removal after operation. The secondary outcomes included the time for consciousness loss during induction, intraoperative hemodynamic data [mean arterial pressure (MAP) and heart rate], the success rate of sedation, the awareness rate during operation, and the incidence of adverse events after admission to postanesthesia care unit(PACU). Results: The Remimazolam group included 12 males and 18 females, aged (5.0±1.4) years. There were 14 males and 16 females in the Propofol group, aged (5.3±1.3) years. The time from drug withdrawal to laryngeal mask removal in Remimazolam group was (6.5±1.2) min, which was shorter than that in Propofol group of (10.7±1.9) min (P<0.001). The time for consciousness loss during induction was (38.1±4.8) s in Remimazolam group, which was longer than that in Propofol group of (31.6±4.9) s (P<0.001). The variability of MAP and heart rate of patients during operation in Remimazolam group was lower than that in Propofol group (all P<0.05). There was no significant difference in sedation success rate, intraoperative awareness and adverse reactions in PACU between the two groups (all P>0.05). Conclusion: In pediatric patients with binocular strabismus during daytime surgery, general anesthesia with remimazolam can shorten the time from drug withdrawal to laryngeal mask removal after operation without increasing the incidence of postoperative adverse reactions and can provide more stable hemodynamics.

[Effectiveness and safety of multimodal analgesia in open gastrostomy in patients with end-stage head and neck cancer].

Objective: To investigate the effectiveness and safety of multimodal analgesia in patients with end-stage head and neck cancer in open gastrostomy surgery. Methods: This was a randomized controlled trial. From June to December 2023, 50 patients with end-stage head and neck cancer who underwent elective open gastrostomy surgery in Beijing Tongren Hospital Affiliated to Capital Medical University were prospectively selected. The patients were divided into multimodal analgesia group and local anesthesia group using the random number table method according to different anesthesia methods, with 25 cases in each group. In multimodal analgesia group, a multimodal analgesia regimen was adopted: ultrasound-guided abdominal wall nerve block (rectus sheath block and transverse abdominis plane block)+intravenous injection of oxycodone+intravenous injection of flurbiprofen axetil and dexamethasone. In local anesthesia group, local infiltration anesthesia with ropivacaine was adopted. The main outcome measure was the incidence of intraoperative pain numeric rating scale (NRS) score>3 points in the two groups. The secondary observation indicators included NRS score and hemodynamic indexes [mean arterial pressure (MAP) and heart rate (HR)] at various time points during surgery [before anesthesia (T0), at the time of incision (T1), 10 minutes after surgery (T2), during gastric body traction (T3), and at the end of surgery (T4)], incidence of adverse reactions, postoperative patient satisfaction score, as well as the NRS scores at rest and activity (coughing) within 24 hours after surgery. Results: The multimodal analgesia group included 21 males and 4 females, aged (61.4±9.9) years. There were 19 males and 6 females in the local anesthesia group, aged (58.6±10.8) years. The incidence of intraoperative NRS score>3 points and the incidence of salvage analgesia in the multimodal analgesia group were both 12.0% (3/25), which were lower than 60.0% (15/25) in the local anesthesia group, and the differences were statistically significant (all P<0.001); The NRS score [M (Q1, Q3)] at T3 in the multimodal analgesia group was 2 (2, 3) points, which were lower than 5 (3, 6) points in the local anesthesia group (P<0.05). There were smaller variabilities in MAP and HR in the multimodal analgesia group than those in the local anesthesia group (all P<0.05). The incidence of intraoperative tachycardia, surgical traction reaction, and nausea in the multimodal analgesia group was lower than that in the local anesthesia group (all P<0.05). The postoperative satisfaction score of patients in the multimodal analgesia group was (9.25±0.71) points, which were higher than (7.33±0.87) points in the local anesthesia group (P<0.001). NRS score during postoperative activity within 24 hours in the multimodal analgesia group were (2.36±0.75) points, which were lower than (3.03±0.81) points of the local anesthesia group (P=0.005). No adverse reactions such as urinary retention, nausea, vomiting and dizziness occurred in both groups. Conclusion: Compared with local anesthesia, the multimodal analgesic strategy could provide better analgesic effect and longer duration, better hemodynamic stability, and fewer intraoperative adverse reactions in patients with end-stage head and neck cancer undergoing open gastrostomy.

[Analysis of clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues].

Objective: To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues. Methods: A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups. Results: There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients (P > 0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant (P = 0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P = 0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ(2)=30.327, P < 0.001 and χ(2)=11.779, P = 0.001). The HBsAg level was higher in group B than that of group A in the second and fourth years, P < 0.05. During the entire treatment process, the HBeAg level was significantly higher in group B than that in group A (P < 0.001). A total of seven cases developed liver cirrhosis or cancer during follow-up, including three cases in group A and four cases in group B (P > 0.05). Conclusion: HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).

[Research progress on the role of hepatitis B virus DNA integration in chronic hepatitis B].

Chronic hepatitis B virus (HBV) infection will greatly contribute to raising the occurrence probability of cirrhosis and hepatocellular carcinoma in patients. Although existing antiviral treatment regimens have a certain effect on delaying disease progression and improving prognosis, it is still not effective in attaining functional cures. Hepatitis B virus DNA integration may be one of the reasons for this phenomenon. Therefore, this paper reviews the possible mechanisms of HBV DNA integration in maintaining chronic inflammation of the liver, evading existing antiviral treatment methods, and inducing hepatocellular carcinoma so as to further deepen the understanding of the role of HBV DNA integration in the occurrence and development of chronic hepatitis B, providing ideas and references for formulating better treatment strategies.

[Clinical features and prognostic analysis of testicular relapse in pediatric acute lymphoblastic leukemia].

Objective: To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis (HR=3.09, 95%CI 1.10-8.72), combined relapse (HR=4.26, 95%CI 1.34-13.52) and CAR-T cell therapy after relapse (HR=0.15,95%CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions: The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

[Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease].

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

[Cryptic COL1A1-PDGFB fusion in dermatofibrosarcoma protuberans: a clinicopathological and genetic analysis].

Objective: To investigate the clinicopathological and cytogenetic features of cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans (CC-DFSP). Methods: Three cases of CC-DFSP diagnosed in West China Hospital, Sichuan University, Chengdu, China from January 2021 to September 2021 were studied. Immunohistochemistry for CD34 and other markers, fluorescence in situ hybridization (FISH) for PDGFB, COL1A1-PDGFB and COL1A1, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing were performed. Results: There were three cases of CC-DFSP, including two females and one male. The patients were 29, 44 and 32 years old, respectively. The sites were abdominal wall, caruncle and scapula. Microscopically, they were poorly circumscribed. The spindle cells of the tumors infiltrated into the whole dermis or subcutaneous tissues, typically arranging in a storiform pattern. Immunohistochemically, the neoplastic cells exhibited diffuse CD34 expression, but were negative for S-100, SMA, and Myogenin. Loss of H3K27me3 was not observed in the tumor cells. The Ki-67 index was 10%-15%. The 3 cases were all negative for PDGFB rearrangement and COL1A1-PDGFB fusion, whereas showing unbalanced rearrangement for COL1A1. Case 1 showed a COL1A1 (exon 31)-PDGFB (exon 2) fusion using NGS, which was further validated through RT-PCR and Sanger sequencing. All patients underwent extended surgical resection. Except for case 3 with recurrence 2 years after surgical resection, the other 2 cases showed no recurrence or metastasis during the follow-up. Conclusions: FISH has shown its validity for detecting PDGFB rearrangement and COL1A1-PDGFB fusion and widely applied in clinical detection. However, for cases with negative routine FISH screening that were highly suspicious for DFSPs, supplementary NGS or at least COL1A1 break-apart FISH screening could be helpful to identify cryptic COL1A1-PDGFB fusions or other variant fusions.

[Effect of gender factor on the effective dose of oxycodone for inhibiting responses to laryngeal mask airway insertion in elderly patients undergoing ophthalmic surgery].

Objective: To evaluate the effect of gender factor on the effective dose of oxycodone for inhibiting responses to laryngeal mask airway (LMA) insertion in elderly patients undergoing ophthalmic surgery. Methods: From June to October 2021, 56 elderly patients, including 26 females and 30 males, aged from 65 to 80 (72±5) years, with a body mass index (BMI) of 18.5-24.9 kg/m2 and American Society of Anesthesiologists (ASA) physical status of Ⅰ or Ⅱ, who underwent elective ophthalmic surgery requiring LMA insertion in the Beijing Tongren Hospital affiliated to Capital Medical University were selected. Patients were divided into two groups according to gender: elderly female group and elderly male group. The modified Dixon sequential method was used. Oxycodone 0.10 mg/kg was injected intravenously in the first patient. Etomidate 0.2 mg/kg and cisatracurium 0.1 mg/kg were administrated 5 min later. After 3 min, the laryngeal mask was placed when the bispectral index (BIS) ≤60. The positive response to LMA insertion was defined as an increase in the maximum mean arterial pressure or the maximum heart rate>20% of the baseline value within 2 min after insertion. When the response to LMA insertion was positive, the dose of oxycodone was increased in the next patient, otherwise the dose was decreased, and the ratio of adjacent dose was 1.1. This process was repeated until the 7th turning point occurred. The half-maximal effective doses (ED50) and 95% confidence intervals (CI) of oxycodone for inhibiting laryngeal mask insertion were calculated and compared between the two groups. Meanwhile, the adverse reactions during anesthesia induction were observed. Results: All 26 patients in the elderly female group completed the test, but one patient in the elderly male group withdrew due to poor alignment of laryngeal mask, and finally 29 patients completed the study. There were 13 cases and 14 cases who had positive response to LMA insertion in the elderly female and male groups, respectively. The ED50 (95%CI) of oxycodone for inhibiting laryngeal mask insertion in the elderly male group was 0.096 (0.083-0.112) mg/kg, which was higher than that in the elderly female group [0.081 (0.073-0.098) mg/kg, P=0.008]. No adverse reactions such as choking cough, muscle tremor, hypoxemia, nausea, vomiting, reflux and aspiration occurred in 55 patients, except that one patient in the elderly female group had transient hypotension after induction, which improved after symptomatic treatment. Conclusion: The ED50 of oxycodone for inhibiting laryngeal mask insertion reaction in ophthalmic surgery is different in patients with different genders, which is 0.096 (0.083-0.112) mg/kg in the elderly male group and 0.081 (0.073-0.098) mg/kg in the elderly female group.

[A real world study on the relationship between drug resistance of targeted therapy and prognosis of HER-2-positive advanced breast cancer].

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.

[The effect and mechanism of exosomes derived from human amniotic epithelial cells on the proliferation and migration of HaCaT in high glucose environment].

Objective: To investigate the effect and mechanism of exosomes derived from human amniotic epithelial cells (hAEC-Exos) on the proliferation and migration of HaCaT in high glucose environment. Methods: The experimental research method was adopted. The amniotic membrane tissue was collected from 10 healthy pregnant women at full term delivery in the Department of Obstetrics and Gynecology of Fujian Medical University Union Hospital from January to June 2019, and the primary human amniotic epithelial cells (hAECs) were isolated. The growth status and morphological changes of the primary hAECs on the 2nd, 4th, and 7th day of culture were observed, and the expressions of the cells surface markers of CD73, CD90, CD29, CD34, and human leukocyte antigen DR (HLA-DR). The 2nd to 4th passages of hAECs were used in the following experiments. The hAEC-Exos were separated by ultracentrifugation method. The HaCaT and hAEC-Exos were co-cultured for 3 h, and the uptake of hAEC-Exos by HaCaT was observed by inverted fluorescence microscopy. The HaCaT were divided into phosphate buffer solution (PBS) group and hAEC-Exos group or dimethyl sulfoxide (DMSO)+PBS group, DMSO+hAEC-Exos group, and LY294002+hAEC-Exos group, which were dealt correspondingly, with 3 wells in each group. Cell counting kit 8 (CCK-8) method was used to detect cell proliferation activity after 0 (immediately), 12, 24, 36, 48, and 60 h of culture. The scratch test was conducted to detect the scratch healing at 0, 24, 48, and 72 h after the scratch, and the scratch healing rate was calculated, respectively. The Transwell experiment was conducted to detect the number of transmembrane cells after 48 h of culture. The Western blotting was used to detect the protein expressions of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), protein kinase B (Akt), and phosphorylated Akt (p-Akt) related to phosphatidylinositol 3-kinase-Akt-mTOR (PI3K-Akt-mTOR) pathway after 24 h of culture. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and independent sample t test. Results: Most of the primary hAECs were oval and uniform in size on the 2nd day of culture. The hAECs were arranged in a typical cobblestone-like monolayer on the 4th and 7th day of culture. The primary hAECs highly expressed CD73, CD90, and CD29 of mesenchymal stem cell related surface markers, and were with no or low expressions of CD34 and HLA-DR of hematopoietic stem cell related surface markers. After 3 h of culture, hAEC-Exos were successfully endocytosed by HaCaT into the cytoplasm and gathered around the nucleus. After 12, 24, 36, 48, and 60 h of culture, the proliferation activity of HaCaT in hAEC-Exos group was significantly higher than that in PBS group (t=3.691, 10.861, 12.121, 10.531, 14.931, P<0.01). At 24, 48, and 72 h after scratch, the scratch healing rates of HaCaT in PBS group were significantly lower than those in hAEC-Exos group (t=3.342, 6.427, 5.485, P<0.05 or P<0.01). After 48 h of culture, the number of transmembrane HaCaT in hAEC-Exos group was significantly more than that in PBS group (t=5.385, P<0.01). After 24 h of culture, the protein expressions of p-mTOR and p-Akt in HaCaT of hAEC-Exos group were significantly higher than those in PBS group (t=4.240, 5.586, P<0.01), while the protein expressions of mTOR and Akt in HaCaT of the two groups were similar (P>0.05). After 24 h of culture, the protein expressions of p-mTOR and p-Akt in HaCaT of DMSO+hAEC-Exos group were significantly higher than those in DMSO+PBS group (t=6.155, 8.338, P<0.01) and LY294002+hAEC-Exos group (t=5.030, 3.960, P<0.01), while the protein expressions of mTOR and Akt in HaCaT of the three groups were similar (P>0.05). The proliferation activity of HaCaT in DMSO+hAEC-Exos group at 12, 24, 36, 48, and 60 h of culture was 0.78±0.05, 1.23±0.07, 1.60±0.09, 1.86±0.09, and 2.03±0.08, which was significantly higher than 0.46±0.04, 0.69±0.07, 0.98±0.08, 1.16±0.08, and 1.26±0.11 in DMSO+PBS group (t=4.376, 7.398, 8.488, 9.766, 10.730, P<0.01). The proliferation activity of HaCaT in DMSO+hAEC-Exos group at 24, 36, 48, and 60 h was significantly higher than 0.96±0.09, 1.20±0.08, 1.39±0.08, and 1.55±0.10 in LY294002+hAEC-Exos group (t=3.639, 5.447, 6.605, 6.693, P<0.05 or P<0.01). The scratch healing rates of HaCaT in DMSO+hAEC-Exos group at 24, 48, and 72 h after scratch were significantly higher than those in DMSO+PBS group (t=4.003, 6.349, 7.714, P<0.01) and LY294002+hAEC-Exos group (t=3.805, 4.676, 4.067, P<0.05 or P<0.01). After 48 h of culture, the number of transmembrane HaCaT in DMSO+hAEC-Exos group was significantly more than that in DMSO+PBS group and LY294002+hAEC-Exos group, respectively (t=7.464, 1.232, P<0.01). Conclusions: PI3K-Akt-mTOR pathway can promote the proliferation and migration of HaCaT in high glucose environment by mediating hAEC-Exos.

[Quality assessment of guidelines on upper gastrointestinal cancer screening].

Objective: To systematically evaluate the methodological quality of screening guidelines for upper gastrointestinal cancer (including esophageal cancer and gastric cancer) both at home and abroad, and provide reference for the update of upper gastrointestinal cancer screening guidelines in China. Methods: Original articles and grey literature published as of 31th Aug 2020 were retrieved using Chinese databases (CNKI, Wanfang, China Biomedical Literature Database and China Guideline Clearinghouse), PubMed, The Cochrane Library and Embase, as well as those from International Agency for Research on Cancer and the International Guide Collaboration Network. The inclusion criteria were being independent guidelines/recommendation documents for upper gastrointestinal cancer screening and meeting the definition of the institute of Medicine, USA. The exclusion criteria were being guideline abstracts, interpretation and evaluation literature, duplicate publications, updated original guidelines, and clinical treatment or practice guidelines for esophageal or gastric cancer. Appraisal of Guidelines for Research and Evaluation (AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) were used to compare and evaluate the quality and reporting standard of esophageal or gastric cancer screening guidelines. Results: A total of 6 esophageal cancer screening guidelines and 5 gastric cancer screening guidelines were included. The results of the AGREE Ⅱ quality evaluation showed that the overall quality of eleven guidelines varied, including two guidelines recommended for "A", one for "B", five for "C" and three for "D". The guidelines had higher scores in the areas of scope and purpose, and clarity. The esophageal cancer screening guidelines had different scores in the areas of rigor and independence. The gastric cancer screening guidelines generally had low scores in the areas of participants and application. The RIGHT evaluation results showed that the quality of eleven guidelines should be improved. The six items with poor report quality were background, evidence, recommendations, review and quality assurance, funding and conflict of interest statement and management and others. Conclusion: The quality of the included upper gastrointestinal cancer screening guidelines is general, and the standardization needs to be strengthened.

[Analysis of bloodstream infections in children with acute myeloid leukemia during induction chemotherapies].

Objective: To explore the clinical features of bloodstream infections (BSI) in children with acute myeloid leukemia (AML) during the first induction chemotherapy. Methods: The clinical data, pathogen of BSI, antibiotic susceptibility in vitro, complications and prognosis of 204 newly diagnosed AML children admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2009 to December 2015 were analyzed retrospectively. χ2 test was used for the comparison between groups and Logistic regression was used for BSI risk factor analysis. Results: Among 204 patients, 116 were males and 88 were females. The age was 8 (ranged from 1 to 14) years. Among them, 170 patients received MAE chemotherapies (etoposide, mitoxantrone and cytarabine) and 25 received IAE chemotherapies (etoposide, idarubicin and cytarabine). The other 9 patients used granulocyte colony stimulating factor (G-CSF)-priming regimen (aclacinomycin or homoharringtonine, cytarabine and G-CSF) for induction treatments. A total of 28 patients experienced BSI and the incidence rate was 13.7% (28/204), 26 of them developed BSI once and 2 patients developed twice. Gram-positive bacteria were predominant pathogens accounting for 53.3% (16/30) while gram-negative bacteria accounting for 40.0% (12/30) and fungal accounted for 6.7% (2/30). The most common detected pathogens were Coagulase negative Staphylococcus (CoNS, 26.7% (8/30)), followed by Streptococcus spp. (13.3% (4/30)) and Escherichia coli (13.3% (4/30)). Among Gram-negative bacteria (GNB), 3 cases showed carbapenem resistance and 2 cases were Stenotrophomonas maltophilia. BSI-related mortality was 28.6% (8/28). Infections caused by drug-resistant GNB or fungi resulted in 6 fatal cases. The incidence rate of BSI in group with severe neutropenia was higher than in group without it (16.6% (25/151) vs. 5.7% (3/53), χ²=3.933, P=0.047). Multivariable analysis showed severe neutropenia at the onset of fever was independent risk factor of BSI (OR=4.258,95%CI 1.097-16.524,P=0.036). Conclusions: During the first induction chemotherapy courses, Gram-positive bacteria cause most of the BSI. Drug-resistant bacteria related infection often result in fatal outcomes. Severe neutropenia is a significant risk factor.

[Analysis of the feasibility and prognostic value of circulating tumor DNA in detecting gene mutations in small cell lung cancer].

Objective: To investigate the feasibility of circulating tumor DNA (ctDNA) in detecting small cell lung cancer (SCLC) gene mutations and its prognostic value in chemotherapy and/or radiotherapy for SCLC patients. Methods: A total of 77 SCLC patients who were admitted to the Department of Thoracic Medical Oncology and the Department of Thoracic Radiation Oncology of Zhejiang Cancer Hospital from July 2016 to November 2019 were included. There were 66 males and 11 females, with a median age of 60 years. Among them, 42 cases were in limited stage (LS) and 35 cases were in extensive stage (ES). Next-generation sequencing (NGS) of patients' plasma ctDNA was performed before treatment. The differences of mutated genes and signaling pathways between LS and ES patients were analyzed and compared. Blood-based tumor mutation burden (bTMB) was calculated according to detected somatic cell mutations. Patients were divided into the high bTMB and the low bTMB groups according to the optimal threshold calculated by R software. Log-rank tests were used to compare progression-free survival (PFS) between the high bTMB and the low bTMB groups. Results: Among the 77 patients, 76 patients had gene mutations detected in their plasma, and the positive rate of ctDNA test was 98%. Among the 76 patients, the genes with the highest mutation frequency were TP53 (89%), RB1 (70%), LRP1B (34%), CREBBP (21%), MLL3 (21%), MLL2 (16%), NOTCH1 (13%), ROS1 (13%), BRCA2 (12%), and PTPRD (12%). The most common mutated genes in LS patients were TP53 (90%), RB1 (68%), LRP1B (24%), MLL2 (22%), and BRCA2 (17%); the most common mutated genes in ES patients were TP53 (89%), RB1 (71%), LRP1B (46%), CREBBP (31%), and MLL3 (29%). The mutation rates of NOTCH1 and CREBBP genes were significantly higher in ES patients (31.4% and 22.9%) than those in LS patients (11.9% and 4.8%) (both P<0.05). Signaling pathway analysis showed that there were more NOTCH pathway gene variations in ES patients. Among LS patients, patients in the high bTMB group (≥ 6.96 mutations/Mb) had a longer PFS than that in the low bTMB group (<6.96 mutations/Mb) (P=0.033); but no such difference was noted in ES patients. Conclusion: Plasma ctDNA sequencing detected SCLC gene mutation profiles similar to those reported in previous literature, thus ctDNA could be used as a tool to study SCLC genomics; the mutation spectra of ES-SCLC and LS-SCLC were different. bTMB has potential prognostic value in LS-SCLCs treated with chemoradiotherapy.

[Research progress of hepatocyte transplantation treatment for alpha-1 antitrypsin deficiency].

Alpha-1 antitrypsin deficiency is an autosomal codominant genetic disease characterized by low levels of alpha-1 antitrypsin in the blood. Clinically, in young patients, it mainly manifests as emphysema, acute/chronic liver injury and liver cancer. The treatment methods include symptomatic treatment and alpha -1 antitrypsin supplementation. However, the existing treatment cannot prevent the liver fibrosis progression. At present, more than ten cases of the disease have been reported in China, but the understanding of this disease is still indecisive. Moreover, there exists no biotherapy drug for this disorder. This article introduces the research progress of hepatocyte transplantation treatment for this disorder.

[Analysis of pathogens and clinical characteristics of bloodstream infection in neutropenic children with hematological malignancies from 2014 to 2018].

Objective: To investigate the microbiologic and clinical characteristics of bloodstream infection in neutropenic pediatric patients with hematological malignancies and provide data support for the rational use of antimicrobial agents in these patients. Methods: A retrospective analysis was performed on the clinical data, pathogen species distribution, and drug sensitivity data of bloodstream infection in neutropenic pediatric patients with hematological malignancies from the Institute of Hematology & Blood Diseases Hospital from January 2014 to December 2018. Results: Total 537 episodes of bloodstream infections occurred in 427 neutropenic children with hematological malignancies; the 30-day all-cause mortality rate was 3.7%. The clinical feature of 44.7% patients with bloodstream infection was only fever, and the pathogenic bacteria were mainly enterobacteriaceae bacteria. Bloodstream infection was usually accompanied by oral mucosa (20.7%) , respiratory tract (20.5%) , and digestive tract (14.3%) symptoms. The distribution of pathogens in patients with different symptoms of bloodstream infection varied (χ(2)=40.561, P=0.001) . Total 550 strains of pathogens were isolated, and the top 5 bacteria were Streptococcus aureus (109 strains, 19.8%) , Escherichia coli (99 strains, 18.0%) , Staphylococcus epidermidis (75 strains, 13.6%) , Klebsiella pneumoniae (67 strains, 12.2%) , and Staphylococcus aureus (32 strains, 5.8%) . The resistance rates of Enterobacteriaceae and Pseudomonas aeruginosa to piperacillin/tazobactam and carbapenems were <5%. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) in Staphylococcus aureus was 9.7%. Conclusion: The proportion of pathogenic bacteria gram-positive cocci and gram-negative bacilli in the bloodstream infection of neutropenic children with hematological malignancies was approximately the same, suggesting that the use of antimicrobial agents should be broad-spectrum. Carbapenems, glycopeptides, and enzyme inhibitor complexes still have good effects.