Effect of Daratumumab combined with Chemotherapy on Immune Function in Patients with Relapsed/Refractory Multiple Myeloma and Observation of its Clinical Efficacy.

Objective: To evaluate the clinical efficacy and immune function of Daratumumab combined with chemotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Methods: Eighty patients with RRMM treated in Xingtai People's Hospital from January, 2020 to December, 2021 were randomly divided into two groups. Patients in the study group were treated with Daratumumab combined with PAD regimen, while patients in the control group were provided with PAD regimen alone. Further comparison was performed on the therapeutic effects, adverse drug reactions, the levels of T lymphocyte subsets CD3+, CD4+, CD8+ and CD4+/CD8+, the positive expression rate of CD38 and the expression level of Notch-1 on the membrane of plasma cells between the two groups. Results: The overall response rate in the study group (67.50%) was significantly better than that in the control group (45.00%). There was no significant difference in the incidence of adverse reactions between the two groups. After treatment, the reviewed levels of CD3+, CD4+ and CD4+/CD8+ were obviously higher in the study group than those in the control group, while the positive expression rate of CD38 and the expression level of Notch one on the membrane of plasma cells were both lower than those in the control group (p<0.05). Conclusion: Daratumumab combined with a PAD regimen is a safe and effective approach that has a definite curative effect on patients with RRMM, which can improve immune function significantly and result in no significant increase in adverse reactions.

[Role of TGF-ß/Smad signaling pathway in diabetic kidney disease and research progress of traditional Chinese medicine intervention].

Diabetic kidney disease is an important microvascular complication of diabetes and the leading cause of end-stage renal disease. Its pathological characteristics mainly include epithelial mesenchymal transition(EMT) in glomerulus, podocyte apoptosis and autophagy, and damage of glomerular filtration barrier. Transforming growth factor-ß(TGF-ß)/Smad signaling pathway is specifically regulated by a variety of mechanisms, and is a classic pathway involved in physiological activities such as apoptosis, proliferation and differentiation. At present, many studies have found that TGF-ß/Smad signaling pathway plays a key role in the pathogenesis of diabetic kidney disease. Traditional Chinese medicine has significant advantages in the treatment of diabetic kidney disease for its multi-component, multi-target and multi-pathway characteristics, and some traditional Chinese medicine extracts, traditional Chinese medicines and traditional Chinese medicine compound prescription improve the renal injury of diabetic kidney disease by regulating TGF-ß/Smad signaling pathway. This study clarified the mechanism of TGF-ß/Smad signaling pathway in diabetic kidney disease by expounding the relationship between the key targets of the pathway and diabetic kidney disease, and summarized the research progress of traditional Chinese medicine in the treatment of diabetic kidney disease by interfering with TGF-ß/Smad signaling pathway in recent years, to provide reference for drug research and clinical treatment of diabetic kidney disease in the future.

Study of fundamental wave depletion in intracavity second harmonic generation.

In this paper, a novel approach to modelling intracavity second harmonic generation (SHG) in periodically poled MgO-doped lithium niobate (PPLN) is presented and verified against experimental results. This approach involves combining the coupled nonlinear wave equations with a rate equation model for a diode-pumped solid-state Nd:YVO4 laser, taking into account both the depletion of the fundamental wave due to the energy conversion from the fundamental wave to the SHG wave and the reduction of the fundamental wave within a laser cavity due to the loss as a result of the SHG nonlinear process. It was shown that the theoretical simulation matched the experimental results well, while also providing physical insight into the importance of the fundamental wave depletion in the intracavity SHG nonlinear processes. The resulting model is computationally simple and has the potential to generalize to the other nonlinear processes such as three-wave mixing and optical parametric oscillation.

[Research Progress of the Effects of Vitamin D Supplementation on Glycemic Control and Adverse Maternal-neonatal Outcomes in Gestational Diabetes Mellitus Patients].

Gestational diabetes mellitus(GDM)can cause blood glucose disorders in pregnant women and result in adverse maternal-neonatal outcomes.Vitamin D(VD)can improve glucose tolerance and insulin sensitivity,and thus theoretically,VD supplementation during pregnancy could improve glycemic control as well as maternal-neonatal outcomes in GDM patients.Although studies have shown that VD deficiency is associated with poor maternal-neonatal outcomes in GDM patients,no solid conclusion has been drawn with regard to the effects of VD supplementation on these patients.Therefore,here we summarized the research progress of the effects of VD supplementation on glycemic control and adverse maternal-neonatal outcomes in GDM patients,in an effort to guide the clinical VD supplementation during pregnancy.

[Metabolomics analysis of Lycium barbarum leaves after Aceria pallida infestation].

Aceria pallida is one of the most common pests in the main production areas of Lycium barbarum in China. The mite mainly feeds on foliage, leading to local tissue deformation and formation of massive galls, which seriously affects the growth and yield of L. barbarum. However, little is known about the influence of galling organisms on plant primary and secondary metabolism. In order to compare the metabolites differences between healthy and the mite infested leaves of wolfberry, and provide a scientific basis for the development and utilization of the galled leaves, L. barbarum seedlings were infested with A. pallida artificially in the laboratory, the metabolites of L. barbarum leaves were determined by LC-MS/MS. Our results showed that the leaves were rich in amino acids and flavonoid compounds. A total of 204 compounds from 16 classes were detected in L. barbarum leaves based on LC-MS/MS. The primary metabolites are mainly amino acids, and the secondary metabolites are mainly organic acids and flavonoids. The content of the metabolite in the leaves of L. barbarum was significantly affected by the mite, 30 metabolites such as flavonoids and phenylpropanoids were significantly changed, 21 metabolites were up-regulated and 9 metabolites were down-regulated significantly. There were 8 compounds which has pharmacological and biological activity, such as eriodictyol, isorhamnetin-3-O-neohesperidoside and scopoletin up-regulated significantly. Based on the above findings, we suggest that the galled leaves of L.barbarum have a potential to be developed in the future.

[Ultrastructure observations on antennal sensilla of Heortia vitessoides the most serious pest of Aquilaria sinensis].

Heortia vitessoides is the most serious pest of Aquilaria sinensis,which is an economically important evergreen tree native to China and is the principal source of Chinese agarwood. In severe infestations,the insects completely eat up the leaves of A. sinensis,causing severe economic losses. In a more recent study,we found that the antennal sensilla of adult play important roles in the host location,mating and oviposition of H. vitessoides. Here,the external morphology of the antennal sensilla of H. vitessoides were examined using scanning electron microscopy. The result showed that the antennae of both sexes of H. vitessoides were filiform in shape,which consist of the scape,pedicel and about 64 segments of flagellomeres. Eight morphological sensilla types were recorded in both sexes,including sensilla trichodea,sensilla chaetica,sensilla basiconica,sensilla coeloconica,sensilla styloconica,sensilla auricillica,sensilla squamiformia and böhm bristle. Major differences were recorded in the distribution and quantity of different sensilla types in each segment of antenna. The sensillas are almost confined to the ventral and lateral surfaces rather than the back side of antennae. Antennal flagella contained the most sensilla while the scape and pedicel segments only contained böhm bristles and sensilla squamiformias. Sensilla trichodea Ⅲ were only found on male antennae. These results are discussed in relation to the possible roles of the sensilla types in the host location,mating and oviposition selection behavior of H. vitessoides.

[Overwintering status and species identification of gall mite in major wolfberry production areas].

To identify the wolfberry gall mite species and their overwintering situation in different wolfberry production areas and to provide a scientific basis for their prevention and control. We investigate the phoresy overwintering situation of gall mite, and identify the species of gall mite. Our results showed that the phoretic gall mite was Aceria pallida in all the production areas. The phoresy of gall mite was a common occurrence in different production areas, and the phoresy probability was above 75%. The phoretic behavior of wolfberry gall mite occurred commonly in the other production areas. The control of this mite in different production areas should pay attention to their phoretic behavior.

[Variance analysis on polysaccharide,total flavonoids and total phenols of Lycium barbarum leaves from different production areas].

To compare the polysaccharides( LBLP),total flavonoids( LBLTF) and total phenols( LBLTP) of Lycium barbarum leaves from 14 production areas from Ningxia,Qinghai and Gansu at different harvesting time. Our results showed that there were significant difference of LBLP,LBLTF and LBLTP among different production areas. The LBLP collected from Xiangride township production area,Dulan,Qinghai was as high as 15. 02%. The LBLTF collected from Dagele township production area,Geermu,Qinghai was as high as28. 63%. The LBLTP collected from Keluke township production area,Delingha,Qinghai was as high as 16. 7%. There were also significant difference of these 3 components between different harvest periods. The average LBLP in May( 10. 20%) was significantly higher than that in June( 8. 49%). However,the average LBLTF( 17. 71%) and LBLTP( 12. 77%) in June was significantly higher than that in May( 14. 15%,11. 19%). The LBLTF and LBLTP have a positive correlation with the altitude of production areas,but there was no significant association between LBLP and altitude. The LBLP,LBLTF and LBLTP in different production areas and harvesting time was significant difference,the results provide some references for furthermore development and utilization of L. barbarum leaves.

Combined Effects of Chronic Obstructive Pulmonary Disease and Depression on Spatial Memory in Old Rats.

Objective To investigate the combined effects of chronic obstructive pulmonary disease (COPD) and depression on spatial memory in old rats, aiming to better understand the comorbidity of the two diseases in geriatric patients. Methods The SD rats were assigned into five groups: adult control group (n=6), elderly control group (n=6), elderly COPD group (n=6), elderly depression group (n=6) and elderly COPD with depression group (n=6). Smoking and chronic unpredictable mild stress (CUMS) with solitary support were used to induce COPD model, depression model, respectively, and the both were applied for the comorbidity model. Learning and memory deficits were assessed by Morris water maze (MWM) test. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum and hippocampus tissue were determined by Xanthinoxidase method and Thiobarbituric acid reaction (TBAR) method, respectively. Results The results of pulmonary histology, lung function, open-field test and sucrose consumption demonstrated the comorbidity models of COPD and depression in elderly rats were successfully established using smoking and CUMS with solitary support. Compared with the elderly control group, the group of COPD with depression had obviously longer time of latency and longer travel distance to reach the platform in MWM test (LSD-t=-10.116, P=0.000; LSD-t=-6.448, P=0.000). The SOD activity in serum and hippocampus decreased significantly (LSD-t=2.629, P=0.014; LSD-t=2.215, P=0.044) and the MDA content in serum and hippocampus increased significantly (LSD-t=-2.140, P=0.042; LSD-t=-2.070, P=0.049) in elderly COPD with depression group. Conclusions COPD in comorbidity of depression could induce spatial memory deficit in old rats. The mechanisms might be related to the overloaded and free radical metabolic imbalance. These results suggest a potential therapeutic target for comorbidity of COPD and depression in geriatric patients.

[Study on membrane type leaf water evaporation inhibitors for improving effect of preventing diseases and pest controlling of Lycium barbarum].

Through indoor and field comparative experiments, the properties of membrane type leaf evaporation inhibitors and its effects on photosynthesis of Lycium barbarum and compatibility and synergistic of pesticide were studied. The evaporation inhibitors and L. barbarum were chosen to investigate the suppression of water evaporation and the compatibility with pesticides. The effect of evaporation inhibitors on photosynthesis of L. barbarum leaves was determined by the chlorophyll fluorescence imaging system. The results showed that water evaporation of L. barbarum leaves of different leaf age were evidently suppressed after treated with evaporation inhibitor. The inhibitor was well compatible with pesticide and effectively improved the pesticide efficacy，and had no significant effect on chlorophyll fluorescence parameters. It is concluded that the evaporation inhibitor has good compatibility with the pesticide, and has remarkable effect of restraining moisture evaporation, which make it can be used for reducing the dosage and improving the efficacy of the pesticide in the field of L. barbarum.

[Threshold temperature and effective accumulative temperature of Periplaneta Americana].

Periplaneta americana is an important medicinal insect. A series of new drugs developed from it have remarkable clinical effects and are in great demand in the market. Because of unclear biology, the quality and yield of P. americana are affected. Understanding the developmental threshold temperature and effective accumulated temperature of P. americana can provide theoretical basis for standardized culture of P.americana. Under climate chamber, the threshold temperature and effective accumulated temperature for egg development of P. americana to were determined through effective accumulated temperature law. The threshold temperature was （15.8±0.71）°C, the effective accumulated temperature was 415.8±38.05 degree days. A model of the relationship between temperature and developmental rates was established.

Analysis of laser speckle reduction utilizing microlens-array-based projection screen.

This paper focuses on the theoretical analyzation of laser speckle reduction by utilizing a microlens array (MLA). A theoretical model was established to describe the screen effect on speckle reduction, taking into account MLA cell size and on-screen projection/detection resolution area size. The relationship between the speckle contrast ratio (SCR) of a projection system and the cell size of an MLA was studied and investigated. A guideline for choosing an MLA that is able to suppress SCR below the threshold of human perception is proposed from the obtained results.

Peptide-Conjugated Quantum Dots Act as the Target Marker for Human Pancreatic Carcinoma Cells.

BACKGROUND/AIMS: In the present study, we describe a novel and straightforward approach to produce a cyclic- arginine-glycine-aspartic (RGD)-peptide-conjugated quantum dot (QD) probe as an ideal target tumor biomarker. Due to its specific structure, the probe can be used for targeted imaging of pancreatic carcinoma cells. METHODS: Pancreatic carcinoma cells were routinely cultured and marked with QD-RGD probe. The QD-RGD probe on the fluorescence-labeled cancer cell was observed by fluorescence microscopy and laser confocal microscopy. Cancer cell viability was detected by MTT assay after culturing with QD-RGD probe. RESULTS: Fluorescence microscopy and laser confocal microscopy displayed that 10nmol/L QD-RGD probe was able to effectively mark pancreatic carcinoma cells. In comparison with organic dyes and fluorescent proteins, the quantum dot-RGD probe had unique optical and electronic properties. CONCLUSION: QD-RGD probe has a low cytotoxicity with an excellent optical property and biocompatibility. These findings support further evaluation of QD-RGD probes for the early detection of pancreatic cancer.

[Evaluation of efficiency of traps baited with frequency trembler grid lamps and trap plants for control Heortia vitessoides infectwed in Aquilaria sinensis].

Heortia vitessoides has been a serious defoliating pest of Aquilaria sinensis forests in recent years.The adults displayed strong tropism to the frequency trembler grid lamps and the nectar source plants.The favorite nectar source plants of H.vitessoides adults as the trap plants and the frequency trembler grid lamps in the integrated management of H.vitessoides were studied in the adult eclosion period through both the laboratory and field.The results showed that Kuhnia rosmarnifolia and Santalum album plants showed strong attraction to the H.vitessoides adults, with significant differences among the different nectar source plants.K.rosmarnifolia and S.album as trap plants with board type of planting area to total planting area of 5%-10%, and the frequency trembler grid lamps trapped significantly more adults of H.vitessoides. These results suggested that the frequency trembler grid lamps and trap plants could play an important role in the integrated management of the pest H.vitessoides of A.sinensis.

[Residue degradation dynamics of spinetoram in wolfberry].

The safety interval period and residue dynamics of two main components (XDE-175-J and XDE-175-L) of spinetoram in wolfberry were measured. Field experiment design and sampling method were carried out according to the "Guideline on pesticide residue trials". The wolfberry samples were extracted with acetonitrile by ultrasonic, and analyzed by UPLC-MS/MS. The wolfberry was sprayed with 6% spinetoram suspension concentrate (SC) at recommended dosage (1 500 times) and doubling dosage (750 times) (one time) at fructescence of wolfberry. The half-lives of spinetoram residue under recommended dosage treatment was 3.65-4.25 d, and all the fresh and dried fruits conform to first order kinetics equation. The dissipation rate was over 95% in fresh and dried fruits at 14 d after application. In conclusion, spinetoram belongs to the easily degradable pesticide type.

[Dissipation dynamics of spirodiclofen in wolfberry fruit].

The dissipation of spirodiclofen in fresh fruit and dry fruit of wolfberry was detected in this study to provide a reference for its safe application.According to Pesticide Residue Test Criteria of China, the open-field experiment was conducted in Zhongning courty of Ningxia province, and the dissipation of spirodiclofen was studied by acetonitrile extraction and HPLC-MS/MS detection. The results showed that the half-lives of spirodiclofen in fresh wolfberry fruit and dry wolfberry fruit were 6.9-11.2 days and 8.5-10.4 days, respectively. Spirodiclofen belongs to the easily degradable pesticide type. According to the maximum residue limits (0.5 mg•kg⁻¹) of spirodiclofen of EU for wolfberry, after recommended dosage being sprayed for once, fresh wolfberry fruit was safe to eat after 5 days, and dry wolfberry fruit was safe to eat after 21 days.

[Preliminary studies on critical control point of traceability system in wolfberry].

As a traditional Chinese medicine, wolfberry (Lycium barbarum) has a long cultivation history and a good industrial development foundation. With the development of wolfberry production, the expansion of cultivation area and the increased attention of governments and consumers on food safety, the quality and safety requirement of wolfberry is higher demanded. The quality tracing and traceability system of production entire processes is the important technology tools to protect the wolfberry safety, and to maintain sustained and healthy development of the wolfberry industry. Thus, this article analyzed the wolfberry quality management from the actual situation, the safety hazard sources were discussed according to the HACCP (hazard analysis and critical control point) and GAP (good agricultural practice for Chinese crude drugs), and to provide a reference for the traceability system of wolfberry.

Calcium sensing receptor promotes cardiac fibroblast proliferation and extracellular matrix secretion.

AIMS: Calcium-sensing receptor (CaR) acts as a G protein coupled receptor that mediates the increase of the intracellular Ca(2+) concentration. The expression of CaR has been confirmed in various cell types, including cardiomyocytes, smooth muscle cells, neurons and vascular endothelial cells. However, whether CaR is expressed and functions in cardiac fibroblasts has remained unknown. The present study investigated whether CaR played a role in cardiac fibroblast proliferation and extracellular matrix (ECM) secretion, both in cultured rat neonatal cardiac fibroblasts and in a model of cardiac hypertrophy induced by isoproterenol (ISO). METHODS AND RESULTS: Immunofluorescence, immunohistochemistry and Western blot analysis revealed the presence of CaR in cardiac fibroblasts. Calcium and calindol, a specific activator of CaR, elevated the intracellular calcium concentration in cardiac fibroblasts. Pretreatment of cardiac fibroblasts with calhex231, a specific inhibitor of CaR, U73122 and 2-APB attenuated the calindol- and extracellular calcium-induced increase in intracellular calcium ([Ca(2+)]i). Cardiac fibroblast proliferation and migration were assessed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), cell count and the cell scratch assay. ECM production was detected by expression of matrix metalloproteinase-3 and -9 (MMP-3 and -9). Activation of CaR promoted cardiac fibroblast proliferation and migration and ECM secretion. More importantly, calhex231, suppressed cardiac fibroblast proliferation and migration and MMP-3 and -9 expression. To further investigate the effect of CaR on cardiac fibrosis, a model of ISO-induced cardiac hypertrophy was established. Pretreatment with calhex231 prevented cardiac fibrosis and decreased the expression of MMP-3 and -9 expression. CONCLUSIONS: Our results are the first report that CaR plays an important role in Ca(2+) signaling involved in cardiac fibrosis through the phospholipase C- inositol 3,4,5 phosphate (PLC-IP3) pathway.

Scattering detection using a photonic-microfluidic integrated device with on-chip collection capabilities.

SU-8-based photonic-microfluidic integrated devices with on-chip beam shaping and collection capabilities were demonstrated in a scattering detection and counting application. Through the proper deployment of the tailored beam geometries via the on-chip excitation optics, excellent CV values were measured for 1, 2, and 5 µm blank beads, 16.4, 11.0, and 12.5%, respectively, coupled with a simple free-space optical detection scheme. The performance of these devices was found dependent on the combination of on-chip, lens-shaped beam geometry and bead size. While very low CVs were obtained when the combination was ideal, a nonideal combination could still result in acceptable CVs for flow cytometry; the reliability was confirmed via devices being able to resolve separate populations of 2.0 and 5.0 µm beads from their mixture with low CV values of 15.9 and 18.5%, respectively. On-chip collection using integrated on-chip optical waveguides was shown to be very reliable in comparison with a free-space collection scheme, yielding a coincident rate of 94.2%. A CV as low as 19.2% was obtained from the on-chip excitation and collection of 5 µm beads when the on-chip lens-shaped beam had a 6.0-µm beam waist.

Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling and pulmonary hypertension by promoting phenotypic modulation of small pulmonary arteries.

Phenotype modulation of pulmonary artery smooth muscle cells (PASMCs) plays an important role during hypoxia-induced vascular remodeling and pulmonary hypertension (PAH). We had previously shown that calcium-sensing receptor (CaSR) is expressed in rat PASMCs. However, little is known about the role of CaSR in phenotypic modulation of PASMCs in hypoxia-induced PAH as well as the underlying mechanisms. In this study, we investigated whether CaSR induces the proliferation of PASMCs in small pulmonary arteries from both rats and human with PAH. PAH was induced by exposing rats to hypoxia for 7-21 days. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVI), the percentage of medial wall thickness to the external diameter (WT %), and cross-sectional total vessel wall area to the total area (WA %) of small pulmonary arteries were determined by hematoxylin and eosin (HE), masson trichrome and Weigert's staining. The protein expressions of matrix metalloproteinase (MMP)-2 and MMP-9, the tissue inhibitors of metalloproteinase (TIMP)-3, CaSR, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated kinase (p-ERK), and smooth muscle cell (SMC) phenotype marker proteins in rat small pulmonary arteries, including calponin, SMα-actin (SMAα), and osteopontin (OPN), were analyzed by immunohistochemistry and Western blotting, respectively. In addition, immunohistochemistry was applied to paraffin-embedded human tissues from lungs of normal human and PAH patients with chronic heart failure (PAH/CHF). Compared with the control group, mPAP, RVI, WT % and WA % in PAH rats were gradually increased with the prolonged hypoxia. At the same time, the expressions of CaSR, MMP-2, MMP-9, TIMP-3, PCNA, OPN, and p-ERK were markedly increased, while the expressions of SMAα and calponin were significantly reduced in lung tissues or small pulmonary arteries of PAH rats. Neomycin (an agonist of CaSR) enhanced but NPS2390 (an antagonist of CaSR) weakened these hypoxic effects. We further found that the expression change of CaSR, PCNA, and SMC phenotypic marker proteins in PAH/CHF lungs was similar to those in PAH rats. Our data suggest that CaSR is involved in the pulmonary vascular remodeling and PAH by promoting phenotypic modulation of small pulmonary arteries.