Objective:To investigate the clinical efficacy of lenalidomide combined with bortezomib and dexamethasone (RVd) regimen in treatment of newly diagnosed multiple myeloma (NDMM) patients and its effect on the levels of regulatory T cells (Treg cells) and natural killer (NK) cells.Methods:Thirty-eight NDMM patients who were admitted to the Second Affiliated Hospital of Bengbu Medical College from September 2019 to May 2022 were selected for a prospective study, and were divided into control group (18 cases) and observation group (20 cases) according to random number table method. The control group was treated with bortezomib+epirubicin+dexamethasone (VAd) regimen, and the observation group was treated with RVd regimen. The efficacy and safety were compared between the two groups. The levels of Treg cells (CD4 + CD25 + FOXP3 +) and NK cells (CD3 - CD56 + CD16 +) before and after treatment in the two groups were detected by flow cytometry, and the results were compared. Results:After 4 courses of treatment, the objective response rate (ORR) of the observation group was 95.0% (19/20), which was higher than that of the control group [77.8% (14/18)], and the difference was statistically significant ( P = 0.016). Before treatment, there was no statistical difference in the levels of Treg cells and NK cells between the two groups ( P values were 0.381 and 0.650). After treatment, the level of Treg cells in the control group increased from (1.5±0.5)% before treatment to (4.7±1.3)% ( P = 0.008), while the level of Treg cells in the observation group increased from (1.4±0.5)% before treatment to (6.8±1.5)% ( P = 0.001), and the level in the observation group was higher than that in the control group ( P = 0.027); the level of NK cells in the control group increased from (16±6)% before treatment to (20±5)% ( P = 0.004), while the level of NK cells in the observation group increased from (16±6)% before treatment to (24±6)% ( P = 0.006), and the level in the observation group was higher than that in the control group ( P = 0.032). The incidence rates of thrombocytopenia and neutropenia in the observation group were higher than those in the control group, and the differences were statistically significant ( P values were 0.012 and 0.027), which was reversible after active treatment. There was no statistical difference in the incidence rates of other adverse reactions (all P>0.05). Conclusions:RVd regimen for NDMM is clinically effective, safe and reliable, and the patients' levels of Treg cells and NK cells elevate after treatment.

Neuromyelitis optica spectrum disorders (NMOSD) are a severe autoimmune inflammatory demyelinating disease of the central nervous system. NMOSD complicated with immune thrombocytopenia (ITP) is rare. This paper reports a case of NMOSD who was misdiagnosed as multiple sclerosis for many years, and then developed thrombocytopenia. ITP was diagnosed by perfect examination. After immunosuppression and thrombopoiesis therapy, the platelets returned to normal. The review of the case and literatures can help to improve the understanding of this kind of disease, timely diagnose and treat patients, and avoid serious complications.

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

Objective: To investigate the association between etheno-DNA adduct and the promoter of DNA methylation levels of cyclin dependent kinase inhibitor 2A (P16), Ras association domain family 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in workers with occupational exposure to diesel engine exhaust (DEE). Methods: We recruited 124 diesel engine testing workers as DEE exposure group and 112 water pump operator in the same area as control group in Henan province in 2012 using cluster sampling. The demographic data were obtained by questionnaire survey; urine after work and venous blood samples were collected from each subject. The urinary etheno-DNA adducts were detected using UPLC-MS/MS, including 1,N6-etheno-2'-deoxyadenosine (εdA) and 3,N4-etheno-2'-deoxycytidine(εdC). The DNA methylation levels of P16, RASSF1A, and MGMT were evaluated using bisulfite-pyrosequencing assay. The percentage of methylation was expressed as the 5-methylcytosine (5mC) over the sum of cytosines (%5mC). Spearman correlation and multiple linear regression were applied to analyze the association between etheno-DNA adducts and DNA methylation of P16, RASSF1A, and MGMT. Results: The median (P₂₅-P₇₅) of urinary εdA level was 230.00 (98.04-470.91) pmol/g creatinine in DEE exposure group, and 102.10 (49.95-194.48) creatinine in control group. The level of εdA was higher in DEE exposure group than control group (P<0.001). DNA methylation levels of P16, RASSF1A and MGMT were 2.04±0.41, 2.19 (1.94-2.51), 2.22 (1.94-2.46)%5mC in exposure group, and 2.19±0.40, 2.41 (2.11-2.67), 2.44 (2.15-2.91)%5mC in control group. DNA methylation levels were lower in exposure group (P values were 0.005, 0.002 and 0.001, respectively). Spearman correlation analysis showed that DNA methylation levels of P16, RASSF1A, and MGMT were negative associated with urinary εdA level (r values were -0.155, -0.137, and -0.198, respectively, P<0.05). No significant correlation was observed between the εdC level and any measured DNA methylation levels (P>0.05) . Multiple linear regression confirmed the negative correlation between εdA and DNA methylation levels of P16, RASSF1A, and MGMT in non-smoking group (β (95%CI) was -0.068 (-0.132--0.003), -0.082 (-0.159--0.004) and -0.048 (-0.090--0.007), P values were 0.039, 0.039 and 0.024, respectively). Moreover, εdC was negative associated with DNA methylation level of MGMT in non-smoking group (β (95%CI) was -0.094 (-0.179--0.008), P=0.032). Conclusion DEE exposure could induce the increased of εdA and decreased of DNA methylation levels of P16, RASSF1A and MGMT.

OBJECTIVE: To establish the cell model using human leukemia cell line HL-60 for exposure of coke oven emissions( COE) in vitro and to explore the mechanism of COE-induced acute toxicity in HL-60 cells. METHODS: HL-60 cells were collected in their logarithmic growth phase and cultured in medium that had final concentrations of COE in 2. 5,5. 0,10. 0 and 20. 0 mg / L for 24 hours. Cell survival rate was examined by CCK-8 assay. The cytotoxicity was evaluated using lactate dehydrogenase release assay. Reactive oxygen species( ROS) production was determined by the 2',7'-dichlorofluorescein diacetate and nitroblue tetrazolium method. The activation of nuclear factor-κB( NF-κB) pathway was evaluated by western blot. RESULTS: With the increasing exposure concentrations of COE,the cytotoxicity of HL-60 cells increased( P < 0. 01),the cell survival rate decreased( P < 0. 01),intracellular ROS decreased( P < 0. 01),whereas extracellular ROS increased( P < 0. 01). These changes had a dose-effect relationship. The levels of phospho-nuclear factor-kappa B p65 and phospho-inhibitor of kappa Bα were higher in all the COE-treated cells compared with untreated cells( P < 0. 05),with no dose-effect relationship. CONCLUSION: COE could cause acute toxicity in HL-60 cells in a doseeffect relationship. The mechanism may be related to the COE-induced in-balanced ROS release and removal,leading to the activation of NF-κB pathway. HL-60 cells can be used as a common cell line for COE hematotoxicity analysis.

Objective To monitor the association between the expression of ve-cadherin and mesentery microcirculation blood flow of sepsis CASP rats,Analysis the relationship of each other.Methods Based on the standard criteria,we established sepsis CASP rats,and the rats were divided into several groups according to the gauge of the vein detained needle in the ascending colon,every group has six rats.The groups consisted of Sepsis A group 22 G(0.9 mm× 25 mm,33 ml/min),sepis B group 20 G(1.1 mm ×32 mm,54 ml/min),sepsis C group 18 G(1.3 mm ×32 mm,80 ml/min),sepsis D group 14 G(2.0 mm ×45 mm,270 ml/min),in addition we established the control group.Real-time observation was performed by microscope on the 6 h's blood velcocity of each sepsis CASP rats group.Then we applied the immunohistochemistry to quantitatively analyze the expression of ve-cadherin of each group.Results The blood velcocity of the mesentery microcirculation in control group was (583.21 ±52.39) μm/s,it was higher compared with the sepsis D group(213.30 ±52.39) μm/s (P ＜0.05),the blood velocity in sepsis A group was (482.71 ± 58.62) μm/s,higher compared with the sepsis D group(P ＜ 0.05).The score of the immunohistochemistry quantitative analysis of mesentery ve-cadherin in control group was 11.17 ±0.34,higher compared with the sepsis D group(5.43 ±0.43)(P ＜0.01).The score of sepsis A group was 10.07 ±0.30,higher compared with the sepsis D group(P＜0.05).Conclusions The expression of ve-cadherin of sepsis CASP rats had positive correlation with the blood velocity of the mesentery microcirculation of sepsis CASP rats,and it can indirectly reflect the degree of the sepsis.

Objective To summarize the clinical outcomes of pectoralis major myocutaneous flap for repairing large defects in oral and maxillofacial area after resection of malignant tumor. Methods The clinical data of 27 patients underwent resection of malignant tumor in oral and maxillofacial area and reconstructed with pectoralis major myocutaneous flap were collected in our hospital from August 1998 to January 2015. The pectoralis major myocutaneous flaps were harvested with sizes ranging from 6 cm × 4 cm to 11 cm × 9 cm. The major myocutaneous flaps were used to reconstruct the defects of oral mucosa in 26 cases, and flap was used to reconstruct the defect of facial skin in 1 case. Seventeen major myocutaneous flaps reached the neck via the subclavicular tunnel, the other 10 were transferred over the clavicle. Results After surgery, 20 flaps (74.1%) were survived completely, 6 were partial necrosis (22.2%) and one was total necrosis (3.7%). Thirteen cases showed postoperative complications (48.1%), in which 10 cases were wound infection (37.0%), including 8 patients with infection at the recipient site and 2 patients with infection at the donor site. The wound infection was found in all of 7 patients with flap necrosis. The other complications included wound dehiscence in 1 patient (3.7%), neck hematoma in 1 patient (3.7%), and lung infection in 1 patient (3.7%). Conclusion In order to avoid the flap necrosis and reduce wound infection at the recipient site, the major myocutaneous flap should be designed based on the characteristics of blood supply, and the vascular pedicle should be protected carefully in the operation.

Objective To investigate the effects of chronic exposure to monochloroacetic acid on the lung function and whole blood counts in occupational exposed workers,and provide new markers for occupational health surveillance.Methods We conducted a cross-sectional molecular epidemiology study of 121 workers who were occupationally exposed to monochloroacetic acid and 69 unexposed workers frequencymatched by age and smoking status from the same geographic region.The lung function was measured by portable lung function instrument,and the lymphocyte subsets were measured by flow eytometry.Linear regression was used to test for differences in the levels of each marker between exposed and control workers.Results FEV1.0/FVC was significantly decreased in both male and female workers exposed to monochloroacetic acid compared to unexposed workers (P＜0.01) after adjusting for potential confounders,which were highly consisteut when stratified by smoking status.Among male workers,monochloroacetic acid exposure was associated with significant decrease in the levels of CD8+ T cells (P＜0.05) and monocytes (P＜0.05),and these statistically significant differences were observed between exposure and control workers only among smokers,not among non-smokers.However,there were no significant differences in the levels of whule blood cells and lymphocyte subsets between two groups anong female workers.Conclusion The chronic monochloroacetic acid exposure was associated with pulmonary dysfunction and immunosuppression,which mainly occurred among nale workers and smokers.

Objective To investigate the effects of chronic exposure to monochloroacetic acid on the lung function and whole blood counts in occupational exposed workers,and provide new markers for occupational health surveillance.Methods We conducted a cross-sectional molecular epidemiology study of 121 workers who were occupationally exposed to monochloroacetic acid and 69 unexposed workers frequencymatched by age and smoking status from the same geographic region.The lung function was measured by portable lung function instrument,and the lymphocyte subsets were measured by flow eytometry.Linear regression was used to test for differences in the levels of each marker between exposed and control workers.Results FEV1.0/FVC was significantly decreased in both male and female workers exposed to monochloroacetic acid compared to unexposed workers (P＜0.01) after adjusting for potential confounders,which were highly consisteut when stratified by smoking status.Among male workers,monochloroacetic acid exposure was associated with significant decrease in the levels of CD8+ T cells (P＜0.05) and monocytes (P＜0.05),and these statistically significant differences were observed between exposure and control workers only among smokers,not among non-smokers.However,there were no significant differences in the levels of whule blood cells and lymphocyte subsets between two groups anong female workers.Conclusion The chronic monochloroacetic acid exposure was associated with pulmonary dysfunction and immunosuppression,which mainly occurred among nale workers and smokers.