[Cytoplasmic light-chain immunofluorescence combined with FISH in bone marrow smears to detect cytogenetic abnormalities in multiple myeloma].

Objective: To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) . Methods: 42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ]. Results: In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively (P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively (P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion: The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.

[Analysis of clinical characteristics and causes of death in 38 patients with pneumoconiosis].

Objective: To analyze the clinical characteristics and causes of death of patients with pneumoconiosis, and to provide evidence for the prevention and management of pneumoconiosis. Methods: From June 2022 to July 2023, 38 dead patients with pneumoconiosis confirmed by Shandong Academy of Occupational Health and Occupational Medicine were selected as the research objects. The clinical data of patients were collected through hospital information system (HIS) and laboratory information management system (LIS) to analyze the basic situation of patients with pneumoconiosis who died, the distribution of industry types, the course of disease, the nature of work, the type of reimbursement, complications/comorbidities, and the direct causes of death. Univariate analysis of variance was used to compare the course of pneumoconiosis death in patients with different age of exposure to dust. Results: Among the 38 patients with pneumoconiosis, there were 37 males and 1 female. The age of exposure to dust was 5-37 (19.29±8.17) years, the duration of disease was 5-41 (20.26±8.53) years, and the age of death was 27-86 (70.42±12.26) years old. There were 10 cases of stage Ⅰ pneumoconiosis, 18 cases of stage Ⅱ, 10 cases of stage Ⅲ pneumoconiosis and 32 cases (84.21%) of silicosis. There were 30 (78.95%) people aged ≥65 years and 8 (21.05%) people aged <65 years. The industry was mainly metal products (18 workers, 47.37%), and the distribution of work was mainly excavation workers (11 workers, 28.95%). The death course of pneumoconiosis patients with 10-<30 years of exposure to dust accounted for 76.32% (29/38). The average course of pneumoconiosis patients with 20-<30 years of exposure to dust was the longest[ (24.00±9.39) years], and there was no statistically significant difference in the average course of disease among different age of exposure to dust groups (F=1.81, P=0.165). The working units of the deceased patients were private enterprises or factories, and the hospitalization expenses were borne by individuals for 21 people (55.26%). The working unit was a state-owned enterprise, and 17 people (44.74%) were reimbursed for hospitalization expenses and work-related injuries. The main comorbidities/complications of pneumoconiosis patients were respiratory infection in 18 cases (47.37%) and chronic pulmonary heart disease (47.37%). The top 3 direct causes of death were pneumoconiosis in 13 cases (34.21%), pulmonary infection in 10 cases (26.32%) and lung cancer in 7 cases (18.42%) . Conclusion: Most of 38 cases of pneumoconiosis patients death diseases such as multiple combination of respiratory system, cardiovascular system, respiratory system disease is a major cause of death in pneumoconiosis patients.

[Related factors of acute symptomatic seizures and epilepsy in children with myelin oligodendrocyte glycoprotein antibody-associated disease].

Objective: To investigate the risk factors of acute symptomatic seizures (ASS) and epilepsy in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: A ambispective cohort study was used including 74 children with MOGAD who were admitted to the Department of Pediatrics of Peking University First Hospital from January 2013 to June 2023 and were followed up. Demographic information, clinical information, treatment status, ASS and epilepsy status were collected. The clinical phenotypes were classified. According to the presence or absence of ASS in the course of disease, the children and the course of disease were divided into groups with and without ASS. Chi-square test, Fisher exact test and Mann Whitney U test were used to analyze the correlation between symptoms and auxiliary examination characteristics and the occurrence of ASS in the two groups of children. Multivariate Logistic regression analysis was used for multivariate analysis. Results: The onset age of the 74 children with MOGAD was 6.58 (3.80, 9.67) years, including 38 females (51.4%) and 36 males (48.6%). The duration of the final follow-up was 2.67 (1.10, 4.12) years, with a total of 239 times acute clinical episodes. ASS occurred in 39.2% (29/74) children during the course of disease and in 29.3% (70/239) of attacks. The common phenotypes were ADEM (67 times (28.0%)), optic neuritis (37 times (15.4%)) and cerebral cortical encephalitis (31 times (13.0%)) in 239 times acute clinical episodes. The incidence of ASS in ADEM and cerebral cortical encephalitis phenotype was 28.4%(19/67) and 100.0% (31/31), respectively. Multivariate analysis showed that cortical involvement on magnetic resonance imaging during clinical attacks was an independent risk factor for ASS (ß=-1.49, OR=0.23) after excluding attacks involving only optic nerve or spinal cord (49 episodes). During the follow-up, 5 children (6.8%) had epilepsy, and all children with epilepsy had multiple clinical attacks of MOGAD and previous ASS. Conclusions: Cortical involvement on magnetic resonance imaging during clinical episodes is an independent risk factor for ASS in children with MOGAD. All MOGAD children with epilepsy had ASS and multiple MOGAD clinical episodes in the past.

[Epidemiological characteristics and drug resistance of diarrheagenic Escherichia coli infection in diarrhea patients in Shanghai, 2016-2022].

Objective: To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods: The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results: In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions: Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.

[Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia].

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

A novel role for endoplasmic reticulum protein ERp72 in the pathogenesis of autoantibody-induced arthritis.

OBJECTIVE: The family of protein disulphide isomerases (PDIs) is a group of oxidoreductases that catalyze the oxidation, reduction and isomerization of disulphide bonds. Recent studies have shown that overexpression of one of the family enzymes, ERp46, potentiates arthritis severity, suggesting that the PDI family participates in arthritis pathogenesis. This study investigated the role of another PDI member, ERp72, in autoantibody-induced arthritis. METHODS: Using the Cre-LoxP method, a mouse strain lacking ERp72 (ERp72-/- mice) was generated. Autoantibody-induced arthritis was induced in both ERp72-/- and ERp72+/+ control mice by injecting serum from K/BxN mice. The synovial inflammation severity was evaluated by joint diameter measurements and histological analysis. Proinflammatory cytokines expression in joint tissue and plasma was assessed by quantitative real-time PCR and ELISA. RESULTS: : The absence of ERp72 in the joints, white blood cells, spleen, thymus, and bone marrow of ERp72-/- mice was confirmed. In the K/BxN serum transfer-induced arthritis (STIA) model, ERp72-/- mice exhibited exacerbated arthritis compared to ERp72+/+ mice, with greater joint swelling, bone and cartilage erosion, and synovial inflammation. Furthermore, ERp72-/- mice exhibited increased expression of IL-1ß, IL-6 and TNF-α in inflamed joint tissues and higher IL-6 levels in plasma. Conversely, IL-10 levels were lower in ERp72-/- mice inflamed joints than in ERp72+/+ mice. Notably, the basal TNF-α level in the blood of ERp72-/- mice was significantly higher than in ERp72+/+ mice. CONCLUSION: ERp72 plays a key role in the negative regulation of autoantibody-induced arthritis.

Analysis of postoperative recurrence-free survival in non-small cell lung cancer patients based on consensus clustering.

AIMS: This study aims to assess whether consensus clustering, based on computed tomography (CT) radiomics from both intratumoral and peritumoral regions, can effectively stratify the risk of non-small cell lung cancer (NSCLC) patients and predict their postoperative recurrence-free survival (RFS). MATERIALS AND METHODS: A retrospective analysis was conducted on the data of surgical patients diagnosed with NSCLC between December 2014 and April 2020. After preprocessing CT images, radiomic features were extracted from a 9-mm region encompassing both the tumor and its peritumoral area. Consensus clustering was utilized to analyze the radiomics features and categorize patients into distinct clusters. A comparison of the differences in clinical pathological characteristics was conducted among the clusters. Kaplan-Meier survival analysis was employed to investigate differences in survival among the clusters. RESULTS: A total of 266 patients were included in this study, and consensus clustering identified three clusters (Cluster 1: n=111, Cluster 2: n=61, Cluster 3: n=94). Multiple clinical risk factors, including pathological TNM staging, programmed cell death ligand 1 (PD-L1), and epidermal growth factor receptor (EGFR) expression status exhibit significant differences among the three clusters. Kaplan-Meier survival analysis demonstrated significant variations in RFS across the clusters (P<0.001). The 3-year cumulative recurrence-free survival rates were 76.5% (95% CI: 68.6-84.4) for Cluster 1, 45.9% (95% CI: 33.4-58.4) for Cluster 2, and 41.5% (95% CI: 31.6-51.5) for Cluster 3. CONCLUSIONS: Consensus clustering of CT radiomics based on intratumoral and peritumoral regions can stratify the risk of postoperative recurrence in patients with NSCLC.

[Investigation of the inhibitory potential of caffeic acid phenethyl ester on prion replication, amplification, and fibril formation in vitro].

Objective: To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrPSc). Methods: The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrPSc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrPSc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results: CCK8 cell viability assay results demonstrated that treatment with 1 µmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 µmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 µmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrPSc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrPSc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10-6 mol/L. Conclusions: CAPE inhibits PrPSc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

[Analysis of myopia status and related factors among primary school students in a certain district of Beijing City in 2022].

Objective: To analyze the current situation of myopia and its related factors among primary school students in a certain district of Beijing City in 2022, and provide a basis for the risk assessment of myopia among primary school students. Method: In June 2022, a cluster sampling method was used to include 376 third-grade students from a primary school in a certain district of Beijing. A questionnaire survey was conducted to collect basic information about students, including eye usage habits, reading and writing postures, and parents' myopia conditions. The examination of students' distant visual acuity and refractive status was performed. A multivariate logistic regression model was used to analyze the related factors of myopia occurrence. Results: The age of 376 primary school students was (8.87±0.417) years old, with 48.40% (182) being male. A total of 196 myopia cases were identified, with a myopia rate of 52.13%. The results of the multivariate logistic regression model analysis showed that students who sometimes read while lying down (OR=2.003, 95%CI: 1.128-3.555), often read while lying down (OR=18.853, 95%CI: 4.512-78.778), had outdoor activity time less than 120 minutes per day (OR=4.937, 95%CI: 2.4464-9.892), were engaged in indoor break activities (OR=4.995, 95%CI: 2.773-8.996), performed eye exercises less than once per day (OR=8.710, 95%CI: 4.464-16.995), had a reading distance from the book less than 30 cm (OR=5.098, 95%CI: 2.410-10.787), occasionally maintained a fist distance from the edge of the desk (OR=1.918, 95%CI: 1.086-3.385), and had high school desks and tables (OR=5.325, 95%CI: 1.465-19.359) could have a higher risk of myopia occurrence, compared with those who never read while lying down, had outdoor activity time more than 120 minutes per day, maintained outdoor break activities, performed eye exercises more than once per day, had a reading distance from the book more than 30 cm, always maintained a fist distance from the edge of the desk, and had short school desks and tables. Conclusion: The incidence rate of myopia among primary school students in a certain district of Beijing City. in 2022 is relatively high. The occurrence of myopia is related to insufficient outdoor activity time and poor eye usage habits.

[Effect of peri-implant soft-tissue phenotype on peri-implant health].

Dental implant is a commonly used therapeutic option for reconstruction of edentulous space. Adequate peri-implant soft tissue is crucial for preventing biological and esthetic complications. Peri-implant soft-tissue phenotypes including supracrestal tissue height, mucosa thickness and keratinized mucosa width could reflect the quality and quantity of peri-implant soft tissue. Different soft-tissue phenotypes might impact the stability of implant restoration through altering the tissue remodeling or inflammatory response. This review will discuss the influence of peri-implant soft-tissue phenotypes on tissue remodeling and inflammatory response after implant placement.

[Clinical management of thrombocytopenia in cirrhosis].

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

[Clinical characteristics and prognostic analysis of 34 patients with primary thyroid lymphoma].

Objective: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) . Methods: A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors. Results: All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis (P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion: PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in the mobilization of autologous peripheral blood stem cells in patients with multiple myeloma].

Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.

[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

A targetable secreted neural protein drives pancreatic cancer metastatic colonization and HIF1a nuclear retention.

Pancreatic ductal adenocarcinoma (PDAC) is an increasingly diagnosed cancer that kills 90% of afflicted patients, with most patients receiving palliative chemotherapy. We identified neuronal pentraxin 1 (NPTX1) as a cancer secreted protein that becomes over-expressed in human and murine PDAC cells during metastatic progression and identified adhesion molecule with Ig like domain 2 (AMIGO2) as its receptor. Molecular, genetic, biochemical and pharmacologic experiments revealed that secreted NPTX1 acts cell-autonomously on the AMIGO2 receptor to drive PDAC metastatic colonization of the liver-the primary site of PDAC metastasis. NPTX1-AMIGO2 signaling enhanced hypoxic growth and was critically required for hypoxia induced factor-1a (HIF1a) nuclear retention and function. NPTX1 is over-expressed in human PDAC tumors and upregulated in liver metastases. Therapeutic targeting of NPTX1 with a high-affinity monoclonal antibody substantially reduced PDAC liver metastatic colonization. We thus identify NPTX1-AMIGO2 as druggable critical upstream regulators of the HIF1a hypoxic response in PDAC.