[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

[Analysis of incidence and risk factors for postoperative venous thromboembolism in patients with stageâ a non-small-cell lung cancer].

Objective: To analyze the incidence and risk factors for postoperative venous thromboembolism(VTE) in patients with stage Ⅰa non-small-cell lung cancer(NSCLC), so as to find evidence for further research of prophylactic anticoagulation. Methods: A total of 132 patients with stage Ⅰa NSCLC, 42 males and 90 females aged from 26 to 79 years with an average of (57±10) years, were retrospectively included in this study. All of them underwent surgical treatment at the Department of Thoracic Surgery of Beijing Chaoyang Hospital Affiliated with Capital Medical University from January 2017 to October 2020. A lower extremity venous ultrasound was performed before and after the operation. Participants were divided into VTE group (n=11) or non-VTE group (n=121) according to whether or not VTE occurred after operation. The surgical conditions, test indicators, imaging information, pathology information were compared between the two groups. Logistic regression analysis was performed to test the associations of VET with putative risks factors in which significant differences were observed. The independent risk factors of VET were determined by this way. Results: Postoperative VTE occurred in 11 cases (8.3%), including 10 cases (90.9%) of deep vein thrombosis (DVT) of lower limbs and 1 case (9.1%) of DVT complicated with pulmonary embolism (PE). The mean age of Patients in the VTE group was older than that in non-VTE Group ((65±9) years vs (57±10) years, P=0.009). On the fifth day after operation, patients in both groups had significantly higher D-dimer level compared with that before operation (3.18(1.55, 5.15) vs 1.54(1.09, 2.57); 2.66(1.17, 4.65) vs 1.34(0.78, 2.04))(both P<0.05). The value of neuron-specific enolase (NSE) and the number of lymph nodes removed during the operation in the VTE group were significantly higher than those in the non-VTE group ((21.54±12.37) vs (14.72±5.75); (19.7±8.2) vs (13.0±7.9)) (both P<0.05). There was no statistically significant difference in the approach of surgery, imaging features (tumor location, vascular cluster signs, etc.), and pathological information (pathological types, etc.) (all P>0.05). The logistic regression analysis showed that the number of lymph nodes removed during the operation was an independent risk factor related to the occurrence of VTE (OR=1.306, 95%CI:1.000-1.600,P<0.05). Conclusions: The incidence of postoperative VTE in patients with stage Ⅰa NSCLC is approximately 8.3%. The number of lymph nodes removed during the operation may be an independent risk factor for postoperative VTE in patients with stage Ⅰa NSCLC.

[Analysis of the self-conscious health status and influencing factors of greenhouse agricultural workers in Beijing suburb].

Objective: To explore the self-conscious health status and related influencing factors of greenhouse agricultural workers in Beijing suburb, so as to provide scientific basis for developing strategies to improve and promote the occupational health conditions of those workers. Methods: According to the production characteristics and scale of the main agricultural districts or counties in the suburb of Beijing, 182 agricultural production personnel were randomly selected to investigate the general situation, occupational situation and self-conscious health status during June 2018 to December 2019. The relevant factors which may affect the self-conscious health conditions were also analyzed by statistical methods. Results: The detection or reported rate of self-conscious health problems was 51.6% (94/182) , among which 29.1% (53/182) workers reported musculoskeletal disorder diseases and 21.4% (39/182) workers reported nervous system diseases. And the self-conscious health status of greenhouse agricultural workers were statistically different in household registration, gender, marital status, working years, mixing or spraying pesticides, smoking or eating in the greenhouse (P<0.05) . Moreover, gender, mixing or spraying pesticide, eating and smoking behavior in the workplace all had an impact on the risk of self-conscious health status of greenhouse agricultural workers (P< 0.05) . Specifically, male is the protective factor to reduce the occurrence of self-conscious symptoms of greenhouse agricultural workers (OR=0.447, 95%CI: 0.234~0.852) , while mixing or spraying pesticides and smoking or eating behaviors in the workplace are the risk factors (OR=1.055, 2.524; 95%CI: 0.503~2.210, 1.107~5.755) . Conclusion: Reducing pesticide use from the source thus minimize related exposure opportunities, strengthening occupational health education thus foster good hygienic habits and improve individual protection consciousness are of great significance for the health protection of greenhouse agricultural workers in Beijing suburb.

Effect of forkhead box O1 (FOXO1) on beta cell development in the human fetal pancreas.

AIMS/HYPOTHESIS: Recent studies have demonstrated that in adult murine beta cells the forkhead box O1 (FOXO1) transcription factor regulates proliferation and stress resistance. However, the role of FOXO1 during pancreatic development remains largely unknown. The present study aimed to characterise the expression of the FOXO1 transcription factor in the early to mid-gestation human fetal pancreas and to understand its role in islet cell development. METHODS: Human (8-21 week fetal age) pancreases were examined using immunohistological, quantitative RT-PCR and western blotting. Isolated human (18-21 week) fetal islet epithelial cell clusters were treated with insulin or glucose, or transfected with FOXO1 small interfering RNA (siRNA). RESULTS: Nuclear and cytoplasmic FOXO1 were widely produced during human fetal endocrine pancreatic development, co-localising in cells with the transcription factors pancreatic and duodenal homeobox 1 (PDX-1) and neurogenin 3 (NGN3) as well as cytokeratin 19 (CK19), insulin and glucagon. Treatment with exogenous insulin (50 nmol/l) induced the nuclear exclusion of FOXO1 in both cytokeratin 19 (CK19)(+) (p < 0.01) and insulin(+) cells (p < 0.05) in parallel with increased phospho-Akt (p < 0.05) production. siRNA knockdown of FOXO1 significantly increased the number of NGN3(+) (p < 0.01) and NK6 homeobox 1 (NKX6-1)(+) (p < 0.05) cells in parallel with increases in insulin gene expression (p < 0.03) and C-peptide(+) cells (p < 0.05) and reduced levels of hairy and enhancer of split 1 (HES1) (p < 0.01). CONCLUSIONS/INTERPRETATION: Our results indicate that FOXO1 may negatively regulate beta cell differentiation in the human fetal pancreas by controlling critical transcription factors, including NGN3 and NKX6-1. These data suggest that the manipulation of FOXO1 levels may be a useful tool for improving cell-based strategies for the treatment of diabetes.

Effect of microRNA-7 on proliferation, invasion, migration and EMT of hepatoma cell line SMMC-7721.

OBJECTIVE: This study aimed to observe the effect of microRNA-7 on the proliferation and migration of human hepatocellular carcinoma cell line SMMC-7721 and its effect on epithelial-mesenchymal transition (EMT). PATIENTS AND METHODS: Eukaryotic expression vector pcDNA3.1(-)-pri-miR-7(p-miR-7) was used to instantaneously transfect human liver cancer cells of SMMC-7721 cells in vitro. The expression of microRNA-7 was detected by RT-qPCR. Western blot was used to detect the expression of EMT marker proteins E-cadherin, ß-catenin, N-cadherin and Vimentin. The proliferation of SMMC-7721 cells was detected by CCK-8 assay, and the invasion and migration ability of cells was detected by transwell assay. RESULTS: Compared with the normal group, the expressions of E-cadherin and ß-catenin in SMMC-7721 cells transfected with miR-7 were significantly increased (p<0.05), while the expressions of N-cadherin and Vimentin were significantly decreased (p<0.05). Meanwhile, the proliferation, invasion and migration ability of the cells were significantly weakened (p<0.05). CONCLUSIONS: The miR-7 can inhibit the proliferation and invasion of human hepatocellular carcinoma cell line SMMC-7721, and its mechanism may be related to upregulation of E-cadherin, ß-catenin protein, and downregulation of N-cadherin and Vimentin proteins.

Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence.

AIMS: Combined hepatocellular cholangiocarcinoma (CHC) is a rare form of primary liver cancer, showing a mixture of hepatocellular and biliary features. Data suggest that most CHC arise from hepatic progenitor cells (HPCs). The aim was to investigate the origin of CHC. METHODS AND RESULTS: Twelve cases of CHC were studied by immunohistochemistry for hepatocytic (hepPar1, alpha-fetoprotein), cholangiocytic cytokeratin [(CK) 7, CK19], hepatic progenitor cell (OV-6), haematopoietic stem cell (c-kit, CD34), as well as CD45 and chromogranin-A markers. The combination of double-fluorescence immunostaining consisted of HepPar1 with CK19, and c-kit with OV-6. All 12 cases demonstrated more or less transitional areas, with strands/trabeculae of small, uniform, oval-shaped cells including scant cytoplasm and hyperchromatic nuclei embedded within a thick, desmoplastic stroma; however, two cases were found to consist entirely of such transitional areas. Simultaneous co-expression of hepPar1 and CK7, or CK19, was demonstrated in 10/12 (83.3%) cases of CHC. c-kit expression was noted in 10/12 (83.3%) cases, of which 7/10 (70%) showed co-expression of OV-6. CONCLUSIONS: The results suggest that CHC are of HPC origin, supporting the concept that human hepatocarcinogenesis may originate from the transformation of HPCs.

[The influence on the function of parathyroid after different thyroid cancer radical operation].

Objective:The aim of this study is to detect the changes of parathyroid hormone and serum calcium levels before and after operation,and evaluate the effect and treatment of parathyroid function after total thyroidectomy.Method:One hundred and seventy-two cases of initial total thyroidectomy were analysed retrospectively,who were divided into simple total thyroidectomy group(A),total thyroidectomy with unilateral central lymph node dissection group(B),and total thyroidectomy with lateral central lymph node dissection group(C).We analyse the preoperative and postoperative serum calcium and parathyroid hormone.Result:In three groups,the serum concentrations of the parathyroid hormone and calcium decreased after operation.The difference was statistically significant between in B group and C group(P<0.05);The hypoparathyroidism had statistical significance between A group and C group(P<0.05).Conclusion:The possibility of hypoparathyroidism and hypocalcemia was increasing with the expansion of the range of operation.Therefore,retain vital recognition of parathyroid gland was very important in the resection of thyroid cancer especially central lymph node dissection.We should reduce the incidence of permanent hypoparathyroidism as far as possible.

[Clinical research and surgical treatment of Hashimoto's disease complicated with papillary thyroid carcinoma].

Objective:To analyze the clinical characteristics of Hashimoto's disease complicated with papillary thyroid carcinoma and research surgical treatment and Hashimoto's disease's effect to papillary thyroid carcinoma. Method:Three hundred and twelve cases of papillary thyroid carcinoma were retrospectively reviewed. Among 70 cases of papillary thyroid carcinoma associated Hashimoto's disease (the observation group), 242 cases of single papillary thyroid carcinoma (the control group). Result:The observation group compared with the control group, there was a significant difference in gender, tumor size, thyroid antibody level and the lymph node metastasis, with statistical significance (P<0.05). Conclusion:Hashimoto's disease is a kind of protective factors of thyroid papillary carcinoma, Hashimoto's disease with coexistent papillary thyroid carcinoma is smaller in tumor diameter and have lower lymph node metastasis. Surgery takes the original operation primary radical and central lymph node dissection, try to avoid the preventive side neck lymph node dissection.

Inhibition of angiogenesis is associated with reduced islet engraftment in diabetic recipient mice.

Rapid reestablishment of a functional microvasculature in transplanted islets is crucial for islet survival and function. To illustrate the importance of angiogenesis in islet engraftment, we took a loss-of-function approach to block angiogenesis in newly transplanted islets and determined the extent of islet engraftment in correlation with islet mass and glycemic control in diabetic recipient mice. Diabetic mice were transplanted with a marginal mass of 200 islets under the renal capsule, followed by once-daily oral administration of saline or 150 mg/kg of C-statin, a potent angiogenic inhibitor, for 14 days. Blood glucose profiles and the amplitude of glucose-stimulated insulin secretion in engrafted islets were determined. At 30 days posttransplant, islet grafts were retrieved for the determination of insulin content and vascular density by immunohistochemistry. When compared to sham-treated controls, diabetic recipient mice receiving a daily oral dose of C-statin exhibited significantly impaired blood glucose profiles and diminished glucose-stimulated insulin secretion in response to glucose challenge, correlating with significantly reduced intragraft insulin content and vascular density. Selective inhibition of angiogenesis was associated with reduced islet mass in diabetic mice. These data extend our view that rapid onset of angiogenesis is crucial for islet survival and engraftment and support the development of therapeutic strategies to stimulate angiogenesis in newly implanted islets for enhancing islet engraftment and improving the outcome of marginal islet transplantation.

[Effects of stimulation of ventromedian area of nucleus hypoglossus on respiratory rhythm in rabbits].

The effects of electrical and chemical stimulation of ventromedian area of nucleus hypoglossus (VMNH) on the electrical activities of diaphragm and genioglossus were studied in 25 urethane-anesthetized, vagotomized rabbits. The experimental results were as follows: (1) A 6 s train of electrical stimulation caused a complete cessation of diaphragmatic activities and an excitation of genioglossal activities. (2) A 0.1 s train of stimulation of the nucleus during the middle or late inspiratory phase could elicit an inspiratory off-switch effect. (3) Microinjection of L-glutamate into VMNH also produced an inhibition of diaphragmatic activities. The above observations suggest that VMNH activity exerts a regulatory effect on respiratory rhythm, and this effect may be involved in the central mechanism of swallowing reflex.

[Modulating effects of nucleus termination nervi trigemini on the activities of genioglossus in rabbits].

The effects of electrical stimulation to the nucleus termination nervi trigemini (NTV) on the activities of genioglossus were studied in 35 rabbits anesthetized with urethane. Electrical stimulation of NTV could cause facilitatory response of genioglossal muscle markedly. Monosodium glutamate microinjected into NTV also produced significant increase of genioglossal activities. The latency of genioglossal response to electrical stimulation of dorsal or ventral part of NTV were respectively 5.9 +/- 0.7 ms and 3.0 +/- 0.4 ms. When the nucleus hypoglossus was stimulated, the latency was 2.2 +/- 0.2 ms. These results suggested that the excitation of NTV could enhance the genioglossal activities so that the resistance of upper airway might be decreased.