Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Objective To investigate the effect of spleen on hepatic macrophages mediated activation of hepatic stellate cells(HSCs)in mice with liver fibrosis.Methods Eighteen male C57BL/6 mice were randomly divided into three groups.Mice in Group A and Group B were injected intraperitoneally with CCl4 to establish liver fibrosis mouse model,while those in Group C were injected with corn oil as normal control.Four weeks later,mice with liver fibrosis received splenectomy(Spx)or sham operation(Sham),respectively.After continuous injection for 2 weeks,liver homogenates(L-Homo)were prepared and liver cells were isolated from the three groups.Expressions of IL-1β,IL-13,TGF-β,TNF-α,PDGF-β and VEGF in the liver homogenates of the three groups were detected by Luminex multifactor analysis.The expressions of these cytokines in liver macrophages(L-Mψ)and other non-parenchymal cells of Sham and Spx mice were analyzed by Real-time quantitative PCR(RT-qPCR)and flow cytometry.Macrophage cell line RAW264.7 or bone marrow-derived macrophages(BMDMs)were treated with liver homogenates from the Sham and Spx groups.Then the differently treated RAW264.7 cells were analyzed for mRNA expressions of cytokines and glutamine metabolism-related molecules by RT-qPCR,or transwell co-cultured with hepatic stellate cell line JS1.After co-culture,the survival and extracellular matrix expression of JS1 cells were analyzed.For comparison,Student's t test(between two groups)or one-way analysis of variance(among multiple groups)were used.Results Compared with normal control group,the concentrations of IL-1β,IL-13,TGF-β and TNF-α in the L-Homo of model group were significantly increased and showed higher levels in Sham group than in Spx group.Moreover,the hepatic macrophages were indicated as the major source of these cytokines.Consistently,macrophages treated with liver homogenate of Sham mice had increased expressions of IL-1β,TGF-β and TNF-α and glutaminase(GLS).After co-culture with macrophages treated with liver homogenate of Sham group rather than Spx group,JS1 expressed higher expressions of α-SMA and collagens.Conclusion The spleen is involved in regulating the secretion of cytokines by hepatic macrophages and enhancing their ability to activate hepatic stellate cells.

Background Previous studies have shown that bisphenol A exposure is associated with the risk of hypertension; however, most of them are cross-sectional and the conclusions are not consistent. Objective To evaluate the association between bisphenol A exposure and the incident risk of hypertension. Methods Based on a nested case-control design involving 1990 subjects derived from the Dongfeng-Tongji cohort, a total of 1080 subjects were included in this study after excluding 887 hypertensive cases at baseline and 23 subjects with missing blood pressure data in follow-up visits. Epidemiological information was collected through questionnaire survey, and serum bisphenol A concentration was detected by high performance liquid chromatography tandem mass spectrometry. Logistic regression model was used to analyze the potential association between serum bisphenol A level and the risk of hypertension incidence, and linear regression model was used to analyze the association between serum bisphenol A level and blood pressure changes between baseline and follow-up. Results The average age of the 1 080 participants was (62.03±7.45) years, of which 41.1% were male. During the follow-up period, a total of 477 (44.2%) developed hypertension. The median serum concentration of bisphenol A in the total population was 3.15 μg·L⁻¹, and the baseline bisphenol A concentration in the new case group (3.24 μg·L⁻¹) was higher than that in the control group (2.98 μg·L⁻¹) (P<0.05). After adjustment for selected covariates, the risk of hypertension increased by 12% (OR=1.12, 95%CI: 1.02, 1.22) for each unit increase in naturally log-transformed bisphenol A; the systolic blood pressure and diastolic blood pressure increased by 1.88 (95%CI: 1.08, 2.69) mmHg and 1.14 (95%CI: 0.68, 1.61) mmHg, respectively. Compared with the low bisphenol A tertile group, the risk of hypertension in the middle tertile and high tertile groups increased by 39% (OR=1.39, 95%CI: 1.01, 1.91) and 40% (OR=1.40, 95%CI: 1.02, 1.93) respectively; the systolic blood pressure increased by 5.91 (95%CI: 3.06, 8.76) mmHg and 5.71 (95%CI: 2.82, 8.59) mmHg, and the diastolic blood pressure increased by 3.09 (95%CI: 3.06, 8.59) mmHg and 2.89 (95%CI: 1.22, 4.57) mmHg, respectively (P_trend<0.001). A positive association between serum bisphenol A level and hypertension was found among those who were female, never/former smokers, never/former drinkers, without family history of hypertension, with physical exercise, and with prehypertension at baseline (P_trend<0.05). There was no interaction between selected stratified variables and bisphenol A levels on hypertension (P_interaction>0.05). Conclusion Bisphenol A exposure is positively associated with the risk of hypertension.

Background Arsenic, cobalt, barium, and other individual metal exposure have been confirmed to be associated with the incidence of kidney stones. However, there are few studies on the association between mixed metal exposure and kidney stones, especially in occupational groups. Objective To investigate the association between mixed metal exposure and kidney stones in an occupational population from a metal smelting plant. Methods A questionnaire survey was conducted to collect sociodemographic characteristics, medical history, and lifestyle information of 1158 mixed metal-exposed workers in a metal smelting plant in Guangdong Province from July 2021 to January 2022. Midstream morning urine samples were collected from the workers, the concentrations of 18 metals including lithium, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, molybdenum, cadmium, cesium, barium, tungsten, titanium, and lead were measured by inductively coupled plasma mass spectrometry, and the urinary mercury levels were measured by cold atomic absorption spectroscopy. Based on predetermined inclusion criteria, a total of 919 mixed metal-exposed workers were included in the study, including 117 workers in the kidney stone group and 802 workers in the non-kidney stone group. With a detection rate of urinary metals greater than 80% as entry criterion, 16 eligible metals were finally included for further analysis. Parametric or non-parametric methods were used to compare the differences between continuous or categorical variables of the non-kidney stone group and the kidney stone group. Logistic regression models were constructed to explore the association between individual metal exposures and kidney stones. Weighted quantile sum (WQS) regression models were used to evaluate the association between mixed metal exposure and kidney stones, as well as the weights of each metal on kidney stones. Then Bayesian kernel machine regression (BKMR) models were used to explore the overall effect of mixed metal exposure on renal calculi and the potential interactions between metals. Results We found that there were significant differences in sex, age, length of service, and body mass Index (BMI) between the non-kidney stone group and the kidney stone group (P<0.05). The urinary concentrations of molybdenum and barium in the kidney stone group were higher than those in the non-kidney stone group, and the differences were statistically significant (P<0.05). The logistic regression models demonstrated that urinary cobalt, arsenic, molybdenum, and barium were positively correlated with the risk of kidney stones (P_trend<0.05). The WQS regression models showed that the mixed exposure to vanadium, cobalt, arsenic, molybdenum, and barium was positively associated with the risk of kidney stones (P<0.05). Among them, molybdenum, arsenic, and barium accounted for 0.391, 0.337, and 0.154, respectively. The BKMR results revealed a positive association between metal mixture exposure and the risk of kidney stones (P<0.05). When other metals were fixed at the 25th, 50th, or 75th percentile, arsenic, molybdenum, cobalt, and barium exhibited significant positive effects on the risk of kidney stones (P<0.05), while vanadium showed a significant negative effect (P<0.05). The interaction analysis demonstrated interactions between barium and cobalt, as well as between vanadium and cobalt (P<0.05). Conclusion In the occupational population of this smelter, occupational mixed metal exposure could increase the risk of kidney stones, and the main metals are molybdenum, arsenic, barium, and cobalt.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

Background Occupational exposure to lead, cadmium, or arsenic is a potential risk factor for blood pressure elevation. Current studies mainly focus on the relationship between a single metal and blood pressure. However, mixed metal exposure often exists in the actual working environment, and the interactive effects of polymetallic interactions on blood pressure and the dose-effect relationship remain unclear yet. Objective To explore the influence proportion of occupational exposure to lead, cadmium, or arsenic on blood pressure and their interactive effects. Methods From January to December 2021, workers from a smelter in southern China were selected. Demographic characteristics, height, weight, and blood pressure of workers were collected through questionnaire and physical examination. At the same time, their urine samples were collected and the levels of urinary lead, urinary cadmium, and urinary arsenic were detected by inductively coupled plasma mass spectrometry, and corrected by urinary creatinine (Cr). Linear regression and logistic regression were used to analyze the relationship between urinary lead, cadmium, and arsenic and blood pressure. Weighted quantile sum (WQS) regression was applied to evaluate the dose-effect relationship between urinary lead, cadmium, and arsenic exposures and blood pressure and the effect weight of each metal on blood pressure. Generalized linear regression and additive/multiplicative scaling were used to identify interactive effects of the three metals on blood pressure. Results A total of 1075 workers were included in this study, with a mean age of (44.68±5.11) years and mean working seniority of (24.66±5.23) years. There were 891 males (88.9%) and 184 were females (17.1%); 24.7% workers were drinkers and 45.7% workers were smokers; 302 workers (28.1%) reported hypertension and 37 of them were taking antihypertensive drugs. The P₅₀ (P₂₅, P₇₅) levels of urinary lead, urinary cadmium, and urinary arsenic were 6.11 (3.71, 11.08), 3.88 (2.68, 5.44), and 26.04 (19.99, 35.11) μg·g⁻¹, respectively. After adjusting for gender, age, working seniority, body mass index, smoking, drinking, and the usage of antihypertensive drugs, systolic and diastolic blood pressure increased by 0.772 and 0.418 mmHg respectively for 10% increase in lead, cadmium, and arsenic mixed exposure. Urinary cadmium, among the three single exposures, had the greatest effect on systolic and diastolic blood pressure, weight (w)=0.523 and 0.551 respectively. The interaction of urinary lead and urinary cadmium was positively correlated with the occurrence of hypertension, multiplicative interaction OR (OR_int)=1.88 (95%CI: 1.09, 3.63), attributable proportion due to interaction (AP)=1.19 (95%CI: 0.40, 8.18). Conclusion This study shows that mixed exposure to lead, cadmium, and arsenic has a positive relationship with blood pressure, in which cadmium plays a major role. Co-exposure to lead and cadmium has a positive interactive effect on hypertension development and systolic blood pressure elevation.

Objective To investigate the treatment results for different regions of posterior cruciate ligament ganglion cyst by surgery.Methods From January 2011 to September 2016,17 patients with posterior cruciate ligament ganglion cysts of the knee were involved in this study.5 cases were located on the femoral side of the ligament (upper 1/3),8 cases were in the middle,and 4 cases were located in the tibia side (lower 1/3),15 cases were operated and 2 were not.A total of 13 cases in the upper 2/3 of the ligament were resected by the anterior two approaches through arthroscopy.two of which were resected by the posterior capsule.2 cases of the tibial lateral cysts were resected by posterior approach.Lysholm scoring system was used to evaluate the knee function before and after operation,and Glasgow curative effect system was used to evaluate the final follow-up results.Results A follow-up 6-24 months in an average of (12.6 ± 3.2) months shows no sign of recurrence at the last follow-up,all patients had no complications such as infection,ligament relaxation,et al.Lysholm score was improved from 57.5 ± 5.2 preoperatively to 92.5 ± 3.6 postoperatively,and the statistical difference is very significant (P ＜ 0.05).And curative effect was evaluated well by Glasgow system.Conclusions Arthroscopic surgery is an effective measure in the treatment of postior cruciate ligament (PCL) ganglion cysts.The upper part of the ligament can be resolved through the anterior approach,and the lower part should be followed by the posterior approach,and if necessary,open the way to handle the external part of the joint.

In order to improve students' overall quality,Biomedical Engineering College of Chongqing Medical University has carried out quality development training in the 6 session of the 450 students.The content includes development projects,the queue training,humanities lectures,inspirational film etc.; the objective is to develop the students' mind,develop their team spirit and interpersonal communication skills.College has recruited and assisted professional instructors in the whole training.The centralized training in specific situations gives students a strong spiritual shock and strong positive energy.Before and after the training we use the same questionnaire to students,the results of which have shown that their comprehensive ability,EQ,and cohesion of the class have been improved.

Infectious disease hospitals are obliged to cope with public health emergencies such as outbreak of infectious diseases.Such hospitals are required to make early detection,early containment,proper management,reasonable preplans,timely training,targeted drills,reasonable deployment of hospital resources,appropriate protection for hospital staff.General hospitals should also cope with prevention and control of infectious diseases to some extent,and work with infectious disease hospitals hand in hand to better cope with such outbreaks.

Objective To explore the method and management of pre-hospital care and raise the level of traffic injuries in pre-hospital care by summarizing the clinical features of death patients with severe tragic accident trauma Methods The basic data of 62 death patients with severe traffic accident trauma was analyzed according to death report statistics of severe traffic accident trauma from January 1st,2005 to December 31th,2008 Results Brain injury death accounted for most of traffic accident trauma death.The mortality rate of brain injury in the wounded wag 8.28%(13/157),but of asphyxia and hemorrhagic shock was 2.55%(4/157),3.18%(5/157)respectively in 2005.With the development of treatment and rescued in time, the mortality rate reduced to 6.11%(11/180),0,0.56%(1/180)in 2008.Conclesions It should be trying to shorten the time of pre-hospital care for pafients with trsffic accident trauma,especially in patients combined with hemorrhagic shock,asphyxia,severe brain injury.It is concluded that rapid and effective pre-hospital care can significantly reduce death rate and self-help or each other rescue training would also be effective to reduce mortality.