[Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study].

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

[Analysis of the relationship between embryo quality at different developmental stages and secondary sex ratio of single live births].

Objective: To investigate the effect of embryo quality at different developmental stages on the secondary sex ratio (SSR) of single live birth neonates. Methods: Data for patients with singleton live births after embryo transferred between January 2016 and January 2022 were retrospectively analyzed. The effect of embryo quality at different development stages on the SSR of 11 713 singleton live births were investigated. The association of SSR and embryo quality at different development stages was examined in univariate analysis and in a multivariate logistic regression model, after adjustment for confounders, using two models (Ⅰ and Ⅱ). Results: The age of both male and female, body mass index of both male and female, basal follicle stimulating hormone and estradiol, smoking of male, methods of insemination, methods of sperm extraction, types of transfer cycle and the number of embryo transferred were not related with SSR (all P>0.05). After adjustment for confounders, the probability of a male live birth was higher after transfer of good-quality blastula than after transfer of poorer-quality blastula (model Ⅰ: aOR=0.73, 95%CI: 0.65-0.82, P<0.001; model Ⅱ: aOR=0.73, 95%CI: 0.65-0.82, P<0.001). The quality of cleavage stage embryo was not associated with SSR (model Ⅰ: aOR=0.99, 95%CI: 0.87-1.13, P=0.937; model Ⅱ: aOR=0.99, 95%CI: 0.87-1.13, P=0.899). Conclusions: The SSR of singleton live births after embryo transfer is not correlated with the quality of cleavage stage embryo, but is correlated with the quality of blastula. Good-quality blastula transfer is more likely to result in a male live birth.

[Effect of activation of Toll-like receptor signaling pathway of peripheral blood mononuclear cell in recombinant hepatitis B surface antigen immune response].

Objective: To explore the effect and mechanism of activation of peripheral blood mononuclear cell (PBMC) Toll-like receptor (TLR3) signaling pathway in recombinant HBsAg (rHBsAg) immune response. Methods: White blood cells were collected from peripheral blood of 13 healthy donors in the preparation of blood products. PBMC was isolated and treated with Poly I:C (Poly I:C group) and PBS (control group) respectively. 48 h later, some cells were collected and the expressions of TLR3 signaling pathway proteins were detected by flow cytometry. After activating (Poly I:C group)/inactivating (control group) TLR3 signaling pathway, rHBsAg was given to both groups for 72 h, and the proportions of DC, T, B cells and their subsets in PBMC were detected by flow cytometry. Paired t-test, paired samples wilcoxon signed-rank test and canonical correlation analyses were used for statistical analysis. Results: The percentage of TLR3 protein-positive cells (19.21%) and protein expression (8 983.95), NF-κB protein expression (26 193.13), the percentage of pNF-κB protein-positive cells (13.73%) and its proportion in NF-κB (16.03%), and the percentage of pIRF3 protein-positive cells (12.64%) and its proportion in IRF3 (21.80%) in Poly I:C group were higher than those in control group (11.54%, 8 086.00, 22 340.66, 8.72%, 9.71%, 9.57%, 19.12%) (P<0.05), and the percentage of TRIF protein-positive cells (89.75%) and protein expression (304 219.54) were higher in Poly I:C group than in the control group (89.64%, 288 149.72) (P>0.05). After PBMC stimulation by rHBsAg, the proportions of mDC (2.90%), pDC (1.80%), B cell (5.31%) and plasma cell (67.71%) in Poly I:C group were significantly higher than those in the control group (1.83%, 0.81%, 4.23%, 58.82%) (P<0.05). Results of canonical correlation analysis showed that the expression of TLR3 protein was positively correlated with the proportions of plasma cells, the expression of pIRF3 protein was positively correlated with the proportions of plasma cells and mDC, and the percentage of pNF-κB protein-positive cells and the percentage of pIRF3 protein-positive cells were positively correlated with the proportion of CD4+T cells. Conclusions: Poly I:C can activate TLR3/TRIF/NF-κB and TLR3/TRIF/IRF3 signaling pathway, promote the function of downstream signaling molecules, and then promote the maturation of DC, induce the immune responses of CD4+T cell, and promote the maturation and activation of B cells and the immune response of rHBsAg.

[Development status of biliary tract imaging technology].

Structure of biliary system is complex as well as various, making troubles for optimal surgical treatment of biliary disease. Remarkable imaging of biliary system helps surgeon evaluating patients and planning surgeries. There are several methods to obtain accurate anatomical information of biliary system, such as X-ray fluoroscopy, MRI and fluorescence-based imaging. Each has its own advantages and disadvantages. Combination of multi-model imaging technologies may improve visual result of anatomical information of biliary tract. More resolvable, legible, and sequential imaging technology of biliary system remains further study. This article reviews various cholangiography methods widely used in the clinical setting.

[Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants].

Objective: To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants. Methods: A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013. Infants were given three doses of hepatitis B vaccine at hour 24, first month and month 6(t)h respectively and were followed up for one year after birth. HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction. Results: Six HBV infection models were detected in HBsAg-positive mothers, and "HBsAg (+), HBeAg (+), anti-HBc (+)" (model one) and "HBsAg (+), anti-HBe (+), anti-HBc (+)" (model two) accounted for 92.5%(208/225) of all the models. Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two, the differences are statistically significant (χ(2)=4.80, P=0.029). The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (χ(2)=4.86, P=0.028). Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598, 95%CI: 0.378-0.947). The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2%, while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (χ(2)=0.22, P=0.640). Conclusions: "HBsAg (+), HBeAg (+), anti-HBc (+)" and "HBsAg (+), anti-HBe(+), anti-HBc (+)" were the common models seen in HBsAg-positive mothers, and the rate of non/low-response to hepatitis B vaccine was different between the two models. HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear. HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.

[Relationship between HBeAg from HBsAg positive mothers and regulatory T cells in neonates and its influence on HBV intrauterine transmission].

Objective: To explore the relationship between HBeAg in HBsAg positive mothers and CD(4)(+)CD(25)(+)Foxp3(+)regulatory T cells (Treg) in newborns, as well as how they would influence the increasing risk on HBV intrauterine transmission. Methods: We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People's Hospital of Taiyuan. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates. The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry (FCM). Results: Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission (OR=4.08, 95%CI: 1.89-8.82). Rates of Treg in newborns born to HBsAg-positive mothers were higher than that of the negative group (Z=2.29, P=0.022). Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers. Frequencies of both Treg and HBeAg in newborns and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant(χ(2)=18.73, P<0.001; χ(2)=181.60, P<0.001; χ(2)=183.09, P<0.001). Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA, mother's HBeAg titers were positively related to the percentage of Treg in their newborns (r(s)=0.19, P=0.039). In addition, the frequencies of Treg were negatively correlated with pDC and CD(4)(+) T cell in their newborns (r(s)=-0.21, P=0.017; r(s)=-0.23, P=0.009). Conclusion: HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.

[Influencing factors for non/low-response to hepatitis-B vaccine in infants of HBsAg positive mothers].

Objective: To investigate the influencing factors for non/low-response to hepatitis B vaccine in infants of HBsAg-positive mothers. Methods: A total of 286 HBsAg-positive pregnant women and their infants were recruited from the Third People's Hospital of Taiyuan during July 2011 to January 2013. The infants were immunized with hepatitis B vaccine according to the 0-1-6 month vaccination schedule and followed up for 12 months. The serum HBV DNA level of mothers, neonates and infants were detected by electro chemilum inescence immunoassay kits and fluorescene quantiative polymerase chain rection. Results: Among 286 infants, the rate of non/low-response to hepatitis B vaccine was 18.53% (53/286). Non-conditional logistic regression analysis indicated that the mother's HBV DNA level ≥1×10(7) copies/ml (OR=2.592, 95%CI: 1.121-5.996) and natural birth (OR=1.932, 95%CI: 1.021-3.654) were the risk factors for non/low-response to hepatitis B vaccine, the risks were 2.592 times and 1.932 times higher compared with the infants whose mothers were HBV DNA negative and the infants whose mothers had cesarean delivery. There was no multiplicative or additive interaction between high HBV DNA load and natural birth (OR=1.055, 95%CI: 0.209-5.321), (RERI=1.617, 95%CI: -4.038-7.272; AP=0.364, 95%CI: -0.527-1.225; SI=1.195, 95%CI: 0.270-13.135). After stratified analysis of mother's HBV DNA level, delivery mode of mothers was not associated with non/low-response of their infants. Conclusion: The mother's load of HBV DNA≥1×10(7) copies/ml might be the factor for non/low-response to hepatitis B vaccine in infants of HBsAg positive mothers.

[Effect of interleukin-6 and interleukin-12 on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers].

Objective: To explore the effect of interleukin-6 (IL-6) and Interleukin-12 (IL-12) on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers. Methods: A total of 91 neonates whose mothers were HBsAg-positive were included and followed up for 12 months. HBV DNA and HBV serological markers in the peripheral blood of the neonates and infants were detected with fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA), and the levels of IL-6 and IL-12 in the peripheral blood of the neonates and infants were detected with enzyme-linked immunosorbent assay (ELISA). Results: The non-/hypo-response rate to hepatitis B vaccination was 35.16% (32/91) in the 91 infants. In the neonatal period and infantile period, the level of IL-6 in non-/hypo-response group was lower than that in high-response group, while the level of IL-12 was higher than that in high-response group, and there was significant difference (P<0.01). From the neonatal period to the infantile period, the level of IL-6 increased, while the level of IL-12 descended in both groups, and there was significant difference (P<0.01). Furthermore, the level of anti-HBs of infants was positively correlated with the level of IL-6 (r(s)=0.70, 0.79, P<0.01), and was negatively correlated with the level of IL-12 (r(s)=-0.71, -0.72, P<0.01) in the neonatal period and the infantile period. From the neonatal period to the infantile period, the increased level of IL-6 was positively associated with the level of anti-HBs (r(s)= -0.74, P<0.01), while the decreased level of IL-12 was negatively associated with the level of anti-HBs (r(s)=-0.42, P<0.01). The level of IL-6 was negatively correlated with the level of IL-12 in the neonatal period and the infantile period (r(s)=-0.68, -0.70, P<0.01). Conclusions: IL-6 might promote the immune response to hepatitis B vaccination in infants whose mothers were HBsAg-positive, while IL-12 might inhibit the immune response. IL-6 and IL-12 would affect the immune response to hepatitis B vaccination in infants of HBsAg-positive mothers at the same time.

[Effect of telbivudine on infants born to HBsAg-positive mothers with non-/hypo-response to hepatitis B vaccine during their second and third trimesters of pregnancy].

Objective: To explore the effect of telbivudine treatment in a prevention program on infants born to HBsAg-positive mothers with non-/hypo-responsiveness to hepatitis B vaccine. Methods: A retrospective cohort study with a total of 321 HBsAg-positive pregnant women and their infants enrolled, was conducted. The mothers were recruited from the Third People' s Hospital of Taiyuan, from July 2011 to January 2013. According to the situation of telbivudine intake in second and third trimesters of pregnancy, the participants were divided into two groups: with telbivudine-treated or as control. The neonates were followed up till the age of 12 months. Maternal, neonatal and infantile HBV-M together with HBV DNA in serum were measured using the electro-chemiluminescence immuno-assay (ECLIA) kits and fluorescence quantitative polymerase chain reaction (FQ-PCR) assay, respectively. Results: The rate of non-/hypo-response was 17.99%. After adjusting the potential confounding factors, the telbivudine treatment on HBsAg-positive mothers in the second and third trimesters of pregnancy seemed as the protective factor for non-/hypo-response to hepatitis B vaccine in infants (aRR=0.119, 95% CI: 0.014-0.974). Levels of IFN-γ and IL-10 in telbivudine-treated group were higher than those in the controls (aRR=8.684, 95%CI: 1.977-38.140; aRR=5.330, 95% CI: 1.278-22.236). When the serum levels of IFN-γ and IL-10 in neonatal peripheral blood were higher than 228.47 pg/ml and 174.05 pg/ml respectively, the infants were less likely to be non-/hypo-responsive to the hepatitis B vaccine (aRR=0.300, 95%CI: 0.105-0.857) (aRR= 0.104, 95% CI: 0.030-0.354). Conclusion: Telbivudine treatment provided for the HBsAg-positive mothers in second and third trimesters of pregnancy were less likely to develop non-/low-responsive to hepatitis B vaccine in infants since IFN-γ and IL-10 might have played a vital role in this process.

[Application of benchmark dose on renal injury in people chronically exposed to lead].

Objective: To screen sensitive indicators of renal injury in lead workers using benchmark dose method. Methods: Of the 486 subjects,116 did not occupationally contact to lead as a control. The blood lead was considered as exposure biomarker, while Uß2-MG and UNAG as effect biomarkers for renal injury. The BMD and BMDL of blood lead were estimated at the 10% benchmark response using BMDS Version 2.6. Results: There was statistical rise in blood lead between the lead group and control group (P<0.05) ; and the blood lead level was divided into four groups by quarterback spacing method, among which UNAG was statistically different (P<0.05) . There was an increased prevalence of abnormal rates of Uß2-MG and UNAG with increasing blood lead concentration (P<0.05) , after trend chi-square test. BMD and BMDL of UNAG and Uß2-MG were 602.784/431.838 µg/L and 130.398/100.981 µg/L caculated by Log-Probit model, respectively. Conclusions: Occupational lead exposure may cause kidney damage, and UNAG could be as a more sensitive marker for monitoring early renal injury than Uß2-MG.

[The relationship of vitamin D receptor gene and blood lead: a meta-analysis].

OBJECTIVE: The correlation of vitamin D receptor (VDR) gene polymorphism and blood lead level had been in doult, which allowed us to write this article. METHODS: Relevant studies about the blood lead and VDR B/b gene polymorphism which published from 1979-2015, were searched in multiple bibliographic databases, such as: CNKI, Wanfang Database, PUBMED. Of the ten references selceted, three were divided into two groups which were classified as different researches, so there were thirteen studies in the meta-analysis. According to the level of blood lead, the studies were analyzed by three groups: normal group, low dose grou and high dose group. The analysis was performed by stata 12.0 software. RESULTS: The blood lead level of VDR B/b genotype was significantly difference in all the three groups (P<0.05) , but there were apparent heterogeneity between normal group and low dose group (P<0.05, I(2)=84.2%; P<0.05, I(2)=88.9%) , except the high dose group (P>0.05, I(2)=12.7%) ; after adjusted, all showed no heterogeneity, and the results were still the same. CONCLUSION: The genotype of VDR may be correlated with blood lead, and the levels of blood lead varied with different genetypes.

[Effect of occupational lead exposure on the blood pressure of lead-exposed workers].

Objective: To investigate the effect of occupational lead exposure on blood pressure and pro-vide supportive evidence of health protection on lead - exposed workers. Methods: 612 workers (452 lead - ex-posed workers, 160 workers as control) were recruited in the battery factory. The blood lead concentration and blood pressure were detected by occupational health examination and biological monitoring. The relationship of blood lead concentration and blood pressure wasanalyzed. Results: The blood lead concentration in the exposed group (249.84±137.74) µg/L was higher than that of the control group (117.25±70.15) µg/L, and the differ-ence was statistically significant (P<0.01) . The difference of abnormal blood pressure and diastolic pressure among the exposed and the control group was statistically significant (P<0.05) . The abnormal blood pressure rate, systolic pressure rate and diastolic pressure rate in the 400~726 µg/L group was higher than that of the 6~199 µg/L and 200~399 µg/L group, and the difference was statistically significant (P<0.01) . Multiple lin-ear regression analysis showed that the influencing factors of the systolic pressure followed by sex, age, length of service and blood lead concentration, diastolic pressure followed by sex, age, smoke and blood lead concen-tration. Conclusion: These findings suggest that long - term occupational lead exposure may result in the in-crease of blood lead concentration.

Microwires fabricated by glass-coated melt spinning.

The glass-coated melt spinning method offers a route for the manufacture of metal filaments with a few micrometers in diameter in a single operation directly from the melt. Cobalt-based amorphous wires, Cu-15.0 atomic percent (at. %) Sn shape-memory wires, and Ni2MnGa (atomic percent) ferromagnetic wires were successfully produced by this method. The cobalt-based amorphous wire is flexible, and Cu-15.0 at. % Sn shape-memory wires have the tensile elongation of 14%. However, because of chemical reaction with glass and oxidation, it is hard to make Cu-Al-Ni shape-memory wires and Ni-Nb-Sn amorphous wires. Conditions for preparing these materials were summarized, and the differences of the solidification processes among glass-coated amorphous cobalt-based wires, Cu-15.0 at. % Sn shape-memory wires, and Ni2MnGa wires were analyzed and discussed.

Morphological and physiological characteristics of transgenic cherry tomato mutant with HBsAg gene.

HBsAg gene was previously introduced into cherry tomato (Lycopersicum esculentum var. cerasiforme) by Agrobacterium-mediated transformation. To investigate the side effect of HBsAg gene in cherry tomato, we analyzed morphological and physiological characteristics of the transgenic mutant N244. The process was performed under field conditions. The results suggested that the mutant N244 exhibited morphological, cytological and physiological variation. First of all, compared with the wild plants NK, N244 had fleshy and dark green leaves, the fewer notches of leaf edge, more adventitious roots and barren seeds. Moreover, the chromosome of N244 were found to be triploid (n = 36) by flow cytometric analysis. Furthermore, N244 has obvious physiological alterations, as compared to NK. It was speculated that transformation of the genes probably led to ploidy variation, and further caused phenotype and physiological changes of plants. Our study will reveal side effects of the mutants, and promote cultivation of transgenic plants in the field.