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Objective To examine the differences in therapy response and confirm the effective regimen for multiple myeloma (MM) patients with t (11; 14)/CD20- or CD20+, for the selection of transplantation as early treatment. Methods To find the differences in therapy response and to confirm the effective regimen for multiple myeloma (MM) patients with t (11; 14)/CD20- or CD20+, for the selection of transplantation as the early treatment. There were three cytogenetics groups: t(11; 14)/CD20- or CD20+ and low-risk profile including normal or cytogenetics other than t (11; 14). Eligible patients received the bortezomib-based induction and lenalidomide-based consolidation/maintenance regimen. Results Patients with t(11;14) gained adverse therapy response for bortezomib induction regimen than other low-risk arm (OR rate: 11.1% versus 84.0% versus 85.2%, P＜0.01). A prospective found that although the patients with t(11;14)/CD20- showed the poor overall response for the bortezomib-based regimen, lenalidomide-based treatment schedule makes them gain a similar therapy advantage comparing with t(11;14)/ CD20+ and other low-risk group in the study The subgroup analyses of progression-free survival(PFS) and overall survival(OS) by continued lenalidomide-based consolidation/maintenance treatment also showed a benefit for lenalidomide therapy compared with observation regardless of cytogenetic risk profile and response at baseline (PFS at 4 years reached 75.0% versus 77.1% versus 84.2%, OS at 4 years was 75.0% versus 88.5% versus 90.4%, respectively). Moreover, the lenalidomide regimen little induced the incidence of fatal complications and was tolerated. There were only 3.2%, 8.4% and 15.8% patients had agranulocytosis, peripheral neuropathy and infection of 3-4 grade. Conclusions Lenalidomide regimen is more effective for t (11, 14)/ CD20- risk MM and t(11;14)/CD20+ and other cytogenetically low-risk MM are consistent in PFS and OS. In addition, the initial response rate of MM patients with unsatisfactory bortezomib treatment can also be improved.

With the implementation of China’s innovation-driven development strategy, the competition among sci-tech talents has become increasingly fierce. Stimulating the innovative vigor of sci-tech talents has become a hot topic in theoretical research and policy practice. Based on the data from 246 questionnaires collected from sci-tech talents in Hebei province, this study explored the influence mechanism of an inclusive organizational climate on innovation input from technological talents and verified the mediating effects of innovation self-efficacy and intrinsic motivation. The results indicate that an inclusive organizational climate has a significant positive impact on innovation input, innovation self-efficacy, and intrinsic motivation of sci-tech talents. Both innovation self-efficacy and intrinsic motivation play a partial mediating role between an inclusive climate and innovation input. This study verified the important role of an inclusive climate in an organization’s human resource management practices and encouraged managers to emphasize enhancing the innovation self-efficacy and intrinsic motivation of sci-tech talents, thereby continuously improving the level of innovation.

Background: Everolimus is beneficial for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). However, some patients developed drug resistance and the well-established predictor for everolimus efficacy was limited. Objectives: The study was designed to evaluate the efficacy of everolimus in different treatment lines and identify several clinicopathological markers to estimate everolimus efficacy in patients with HR+/HER2− ABC. Design: This was a retrospective and multicenter study. Methods: Between 2014 and 2022, more than 2000 patients with tumors who received everolimus were collected from multiple cancer centers in China (National Cancer Center, Chinese PLA General Hospital, Peking University Cancer Hospital & Institute). A training cohort and two validation cohorts were developed. Results: The training cohort included 338 patients. The median progression-free survival (PFS) for everolimus was 5.6 months, with an objective response rate of 25.1% and a clinical benefit rate of 54.4%. PFS was significantly worse from first-line (1L) to second-line (2L) to third-line (3L), with PFS1L for 13.5 months, PFS2L for 6.1 months, and PFS3L for 4.1 months (p = 2.9e−6, hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.61–0.82). The clinicopathological characteristics, including post-1L everolimus treatment, Ki67 index of more than 40%, more than two metastatic sites at first recurrence, and receiving adjuvant chemotherapy, were independent risk factors for PFS. A predictive model for everolimus efficacy was established using these four factors. In the low-risk group, patients achieved a median PFS of 12.6 months, significantly longer compared to 2.7 months for those in the high-risk group (p = 2.4e−64, HR = 9.41, 95% CI = 7.05–12.56). The area under the curve was 0.96, 0.95, and 0.94 for 6-month, 1-year, and 3-year PFS, respectively. Internal validation cohort (PFS 18.4 vs 3.1 months, p = 3.6e−11, HR = 3.78, 95% CI = 2.49–5.74) and external validation cohort (PFS 13.5 vs 3.1 months, p = 2.9e−10, HR = 11.53, 95% CI = 4.68–28.37) confirmed its power for estimating clinical benefits of everolimus. Conclusion: A predictive model was successfully established to predict survival outcomes for everolimus in patients with HR+/HER2− ABC, which may provide references for the management of everolimus in Chinese patients with HR+/HER2− ABC. [ABSTRACT FROM AUTHOR]

Purpose: Persistent human papillomavirus infection is thought to be the main cause of the cervical cancer development along with inflammation. However, the potential mechanisms of action of the inflammatory factors in cervical cancer remain unclear. Therefore, this study aimed to assess the relationship between inflammatory factor levels and cervical cancer risk using a two-sample bidirectional Mendelian randomization (MR). Patients and Methods: MR utilizes single nucleotide polymorphisms as a tool to infer potential causal relationships between exposure factors and outcomes. Datasets for 91 inflammatory factors and cervical cancer were obtained from publicly available pooled data. The inverse variance weighted method was used as the main method and MR-Egger, weighted median, simple mode, and weighted mode were used as auxiliary analyses. Results were tested for robustness using sensitivity tests. In addition, we assessed the possibility of reverse causality between cervical cancer and the derived inflammatory factors by performing a reverse MR analysis. Finally, a preliminary experimental validation was performed. Results: We found that artemin and monocyte chemoattractant protein-4 levels were significantly correlated with elevated cervical cancer risk (β: 0.0024, P = 0.002 and β: 0.0010, P = 0.016, respectively. In contrast, interleukin-18 and interleukin-22 receptor subunit alpha-1 levels were associated with reduced risk of cervical cancer (β: − 0.0010, P = 0.029 and β: − 0.0021, P = 0.046, respectively). Sensitivity analyses were more robust as no significant heterogeneity or horizontal pleiotropy was observed. Conclusion: A significant causal relationship was found between the four inflammatory factors and the risk of cervical cancer, providing new evidence of their clinical implications in cervical cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

BackgroundAutoimmune neutropenia (AIN) is a common chronic neutropenia in children, but it in children has been rarely reported.ObjectiveTo analyse clinical characteristics, diagnosis, treatment, and follow-up of children with AIN, aiming at providing support for clinicians.MethodsA retrospective design was used. Participants were 22 children with AIN recruited from Department of Pediatrics, Peking University First Hospital from 2012 to 2020. Their clinical and follow-up data were collected and analyzed.ResultsOf the 22 cases, 15 were male and 7 were female; with 6 months as the median initial diagnosis age. Among the results of 82 routine blood tests performed for all cases, severe, moderate and mild neutropenia accounted for 62.2% (51/82) , 30.5% (25/82) , and 7.3% (6/82) , respectively. Two cases (9.1%) were diagnosed with moderate neutropenia and other 20 (90.1%) were diagnosed with severe neutropenia by the lowest absolute neutrophil count (ANC) . Six children (27.3%) also had other clinical manifestations besides neutropenia. Twelve cases (54.5%) underwent the examination of bone marrow cell morphologies. Six cases (27.3%) underwent gene test. 95.5% of the cases had infections, and 54.5% of them had severe infections, but no life-threatening infections. The leading pathogen of infections was virus. The upper respiratory tract was the most common infected area. By the end of September 2021, the ANC of 11 cases returned to the normal level, and the median of AIN of them was 25 (range: 7-42) months.ConclusionMost AIN children had moderate to severe neutropenia, and they were prone to infections mostly caused by virus, and the most usually were upper respiratory tract infections, but rarely life-threatening. The median duration of AIN, a self-limited disease, for our reported cases was 25 months.

BackgroundShwachman-Diamond syndrome (SDS) is a rare autosomal recessive genetic disease that has complex and various clinical presentations. With the increase in application and clinical sensitivity of genome sequencing, the diagnoses of SDS in children and adults using genome sequencing have increased significantly, but most Chinese SDS patients have not received systematic and standardized treatment after diagnosis.ObjectiveTo analyze the clinical characteristics, diagnosis and treatment of three children with SDS, expecting to improve clinicians' recognition of this disease, reduce the possibilities of missed diagnosis and misdiagnosis, and standardize the treatment of diagnosed children.MethodsData of three children with SDS were collected from Department of Pediatrics, Peking University First Hospital from October 2018 to October 2020, including clinical manifestations, laboratory examination, gene analysis, treatment and follow-up, and were analyzed. In combination with the review of other relevant literature, the diagnosis and treatment of pediatric cases of SDS were summarized.ResultsAmong the three cases encountered and treated by us, two were female and one was male. All of them had recurrent infection, fatty diarrhea, short stature and malnutrition. Case 2 also had syndactyly. Auxiliary tests suggested that all these cases had neutropenia and abnormal liver function. Besides that, case 1 also had severe anemia, and case 2 had thrombocytopenia. Two compound heterozygous mutations of SBDS gene, that is, c.258 + 2T>C and c.184A>T, were found in all three cases. For treatment, all three patients were given pancreatic enzyme replacement therapy, nutritional support, and hepatoprotective treatment. The anemia of case 1, which was dependent on suspended red blood cell transfusion, was obviously improved after low-dose prednisone treatment.ConclusionSDS is a disease with multiple systems involved. Gene detection is helpful to the early diagnosis of SDS. Comprehensive, multidisciplinary treatment is needed. Hematopoietic stem cell transplantation with reduced dose pretreatment can improve some clinical manifestations, but the transplantation indications should be strictly controlled. Low dose and short course of glucocorticoid could be used to reduce the dependence on blood products for those with low erythropoiesis and no hematopoietic stem cell transplantation conditions.