OBJECTIVE: To retrospectively analyze the characteristics and influencing factors of COVID-19 infection in patients with multiple myeloma (MM) who underwent autologous hematopoietic stem cell transplantation (AHSCT). METHODS: The clinical data of MM patients who underwent AHSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 26, 2021 to December 26, 2022 were collected. The onset of COVID-19 infection, corresponding symptoms and laboratory tests were followed up in outpatient or by the means of telephone contact and online questionnaires. Related analysis was then performed. RESULTS: This study included 96 patients, and 72 cases among them were infected with COVID-19 while 24 cases were uninfected. Logistic regression analysis showed that vaccination did not significantly reduce the risk of COVID-19 infection, but patients who received two doses of the vaccine had a lower risk of developing moderate and severe disease than those who did not receive or received one dose (OR =0.06, P =0.029). Patients who received daratumumab before had a higher risk of COVID-19 infection (OR =5.78, P =0.039), while those with a history of immunomodulatory drugs (IMiDs) had the opposite effect (OR =0.31, P =0.028). The use of both drugs did not affect the severity of COVID-19 infection. CONCLUSION For MM patients undergoing AHSCT as first-line chemotherapy, COVID-19 vaccination does not significantly reduce the infection rate, but it plays a role in preventing moderate and severe cases. The application of antineoplastic drugs with different mechanisms has a certain impact on the susceptibility to the COVID-19, which should be considered comprehensively when creating treatment plans.
Humans ; Multiple Myeloma/complications* ; COVID-19/epidemiology* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Antibodies, Monoclonal

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Objective:To investigate the feasibility of 3.0 T glutamate chemical exchange saturation transfer (GluCEST) imaging in evaluating renal redox metabolism in renal ischemia-reperfusion injury (IRI).Methods:Rabbits in the IRI group ( n=56) underwent surgery by clamping the left renal artery for 45 min and then releasing to establish IRI. Rabbits in the sham group ( n=8) underwent the same operation without clamping the left renal artery. GluCEST MRI was performed before and at 1 h, 12 h, 1 day, 3 days, 7 days, and 14 days after the operations, with eight rabbits in the IRI group sacrificed immediately after each scanning and eight in the sham group sacrificed at 14 days after scanning. The left kidneys were removed for histopathological examination and reactive oxygen species (ROS) fluorescence staining. Differences in the magnetic resonance ratio asymmetry (MTR asym) of the renal cortex and outer medulla among different groups were compared. Correlations between the MTR asym and ROS were analyzed. Results:The MTR asym of the renal cortex in the sham and IRI subgroups were higher than that of the outer medulla ( t=8.16, P<0.001; t=4.78, P=0.002; t=4.94, P=0.002; t=5.76, P=0.001, t=6.68, P<0.001; t=6.40, P<0.001; t=5.16, P=0.001; t=3.30, P=0.013). The MTR asym of the renal cortex and outer medulla in the IRI-1h, IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups were lower than in the sham and IRI-pre groups (all P<0.05). The MTR asym of the renal cortex and outer medulla in the IRI-1h group were lower than in the IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups (all P<0.05). The MTR asym of the renal cortex in the IRI-12h group was lower than in the IRI-7d and IRI-14d groups (1.84%±0.09% vs.2.42%±0.19%, 2.41%±0.31%, all P<0.05). The MTR asym of the renal cortex in the IRI-1d group was lower than in the IRI-7d group (1.99%±0.17% vs. 2.42%±0.19%, P=0.008). The MTR asym of the outer medulla in the IRI-12h group was lower than in the IRI-3d, IRI-7d, and IRI-14d groups (1.32%±0.27% vs. 1.79%±0.31%, 1.98%±0.18%, 1.66%±0.40%, respectively, all P<0.05]. The MTR asym of the outer medulla in the IRI-7d group was higher than in the IRI-1d and IRI-14d groups (1.98%±0.18% vs. 1.52%±0.31%, 1.66%±0.40%, all P<0.05). The MTR asym of the renal cortex and outer medulla had a strong negative correlation with the mean fluorescence intensity of ROS ( ρ=-0.889, P<0.001; ρ=-0.784, P<0.001). Conclusion:3.0 T GluCEST imaging can indirectly reflect the changes of renal redox metabolism in renal IRI.

Objective To study the evaluation value of lung injury score(LIS)and advanced glycation end products(AGEs)expression levels on the prognosis of elderly patients with sepsis-related acute lung injury/acute respiratory distress syndrome(ALI/ARDS).Methods A total of 98 elderly patients with sepsis-related ALI/ARDS admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University from March 2019 to April 2021 were selected as the research group,and the patients were divided into two sub-groups according to their survival within 30 d after admission:the survival group(55 cases)and the death group(43 cases).Another 51 elderly patients with non-ALI/ARDS sepsis admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University in the same period were selected as the control group.After admission,the clinical data of patients were recorded,and the levels of serum creatinine,troponin I,B-type brain natriuretic peptide(BNP),serum C-reactive protein(CRP)and procalcitonin(PCT)were de-tected.Enzyme-linked immunosorbent assay was used to determine the levels of AGEs in patients'serum.The LIS score was evaluated by LIS scale.With clinical factors as independent variables and prognosis as dependent variables,Logistic regression curve was used to analyze the death factors of elderly sepsis-related ALI/ARDS patients.Results AGEs levels,LIS scores,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores decreased sequentially in the death group,survival group,and control group(all P<0.05).The levels of lactic acid,blood glucose,troponin I,PCT,BNP and CRP in arterial blood of patients in the death group were significantly higher than those in the survival group and the control group(P<0.05).The results showed that arterial lactate,blood glucose,troponin I,PCT,BNP,CRP,AGEs,APACHE Ⅱ score,and LIS score were all independent risk factors for mortality in elderly sepsis-related ALI/ARDS patients(P<0.05).The area under the curve(AUC)of LIS score predicting prognosis in elderly sepsis-related ALI/ARDS pa-tients was 0.857(95%CI:0.821-0.911),and AUC of serum AGEs was 0.861(95%CI:0.809-0.908).LIS score and AGEs level had certain predictive value for the prognosis of elderly sepsis-related ALI/ARDS pa-tients.Conclusion The LIS score and AGEs level of the elderly patients with sepsis-related ALI/ARDS are independent risk factors of death,which have important predictive value for prognosis.

Objective:To explore the feasibility of chemical exchange saturation transfer (CEST) imaging at 3.0 T MRI in quantifying renal redox metabolism in vitro models and experimental animals.Methods:Redox metabolites in vitro models with physiological concentrations were prepared, including reduced metabolites (glutamate, alanine, glutathione) and oxidized metabolites (2-ketoglutarate, pyruvate, glutathione disulfide, ammonium hydroxide). CEST examinations were performed at 3.0 T MRI. The imaging parameters were as follows: CEST images with different saturation pulse intensity (B 1) (1, 2, 3, 4 μT) and a fixed radio frequency (RF) duration of 2 000 ms; CEST images with different RF durations (1 500 and 2 000 ms) were acquired with a fixed B 1 value of 2 μT to obtain the optimal scanning parameters. CEST examinations with optimized parameters were performed on the left kidneys of seven healthy rabbits, and the differences in magnetic resonance ratio asymmetry (MTR asym) between rabbit renal cortex and outer medulla were measured. A paired t-test was used to compare the differences. Results:The optimal B 1 for CEST examination of redox metabolites was 2 μT, and the optimal RF duration was 2 000 ms. The MTR asym peaks of glutathione disulfide, glutathione, glutamic acid, and alanine were at 3.75, 3.5, 3, and 1.5 ppm, respectively. The MTR asym peaks of pyruvate, 2-ketoglutarate, and ammonium hydroxide were at 1 ppm. The MTR asym peak values of reduced metabolites were higher than those of oxidized metabolites. When the B 1 value was 2 μT and the RF duration was 2 000 ms, the MTR asym signal of the renal cortex was (2.60±1.10) %, (2.86±1.32) %, (3.04±1.06) %, and (2.98±0.91) % at 1, 3, 3.5, and 3.75 ppm, respectively. The MTR asym signal of the outer medulla was (1.00±0.56) %, (2.43±0.94) %, (2.29±0.88) % and (1.98±0.58) %, respectively. The MTR asym signal of the renal cortex was higher than that of the outer medulla, and the differences were statistically significant ( t=3.04, P=0.023; t=2.56, P=0.043; t=3.50, P=0.013; t=3.45, P=0.014). Conclusion:CEST imaging at 3.0 T MRI can be used to quantitatively evaluate redox metabolism of healthy rabbit kidneys in vitro model and normal experimental rabbits.

To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6％(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4％in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.

Objective:To investigate the effect of sodium tanshinone ⅡA sulfonate (STS) on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by H 2O 2 and its possible mechanism. Methods:From November 2021 to September 2022, HUVECs were used as the research subjects at Wuxi Ninth People’s Hospital. The experiment was divided into four groups: the blank control group (normal condition), blank + STS group, H 2O 2 group and H 2O 2 + STS group. When the cells reached 80% fusion, 500.00 μmol/L of H 2O 2 was added to H 2O 2 group and H 2O 2 + STS group for 3 hours, and then the medium containing 500.00 μmol/L H 2O 2 was removed. After that, the blank+ STS group and the H 2O 2+ STS group were each supplemented with 5.00 μg/ml of STS and co-cultured with HUVECs for 24 hours. CCK-8 was used to assess the impact of STS at various concentrations (0.00, 0.05, 0.50, 5.00, 50.00, 500.00 μg/ml) on the proliferation of HUVECs. DNA damage-positive cells were detected with TUNEL staining. The expression of NOD-like receptor protein 3 (NLRP3) was detected using real-time PCR (RT-PCR) to investigate the optimal concentration of pyroptosis induced by H 2O 2. A detection kit was used to measure the expression of reactive oxygen species (ROS) induced by H 2O 2. The effect of STS on the migration and tube formation of HUVECs during pyroptosis was examined using a cell scratch test and a matrix gel tube formation test. The expressions of NLRP3, caspase-1, interleukin-18, and interleukin-1β were detected using RT-PCR and Western blotting. Repeated measures ANOVA was used to compare the concentrations at different time points, t-tests were used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. P<0.05 was considered statistically significant. Results:STS below 50.00 μg/ml had no effect on the proliferation of HUVECs, while 500.00 μmol/L H 2O 2 had the most significant effect on inducing pyroptosis in HUVECs. TUNEL staining showed that compared with the control group, the number of TUNEL-positive cells in H 2O 2 group was significantly increased, and the difference was statistically significant ( P<0.01). However, there was no significant difference in the number of TUNEL-positive cells in the H 2O 2+ STS group ( P>0.05). The results of ROS detection showed that compared with the H 2O 2 group, intracellular ROS levels in the H 2O 2+ STS group was significantly decreased, and the difference was statistically significant ( P<0.01). Cell scratch and tube formation in vitro experiments showed that compared with the control group, cell mobility and tube formation ability were significantly decreased in the H 2O 2 group (all P<0.01), and there was no statistical significance in the H 2O 2+ STS group (all P>0.05). RT-PCR and Western blotting results showed that, compared with the H 2O 2 group, the expression of pyroptosis-related factors in the H 2O 2+ STS group was significantly decreased (all P<0.05). Conclusion:STS can inhibit the excessive production of ROS, promote the cell migration and tubular formation of HUVECs after pyroptosis induction, and alleviate H 2O 2-induced pyroptosis of HUVECs, thereby promoting angiogenesis.

Objective:To investigate the effect of sodium tanshinone ⅡA sulfonate (STS) on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by H 2O 2 and its possible mechanism. Methods:From November 2021 to September 2022, HUVECs were used as the research subjects at Wuxi Ninth People’s Hospital. The experiment was divided into four groups: the blank control group (normal condition), blank + STS group, H 2O 2 group and H 2O 2 + STS group. When the cells reached 80% fusion, 500.00 μmol/L of H 2O 2 was added to H 2O 2 group and H 2O 2 + STS group for 3 hours, and then the medium containing 500.00 μmol/L H 2O 2 was removed. After that, the blank+ STS group and the H 2O 2+ STS group were each supplemented with 5.00 μg/ml of STS and co-cultured with HUVECs for 24 hours. CCK-8 was used to assess the impact of STS at various concentrations (0.00, 0.05, 0.50, 5.00, 50.00, 500.00 μg/ml) on the proliferation of HUVECs. DNA damage-positive cells were detected with TUNEL staining. The expression of NOD-like receptor protein 3 (NLRP3) was detected using real-time PCR (RT-PCR) to investigate the optimal concentration of pyroptosis induced by H 2O 2. A detection kit was used to measure the expression of reactive oxygen species (ROS) induced by H 2O 2. The effect of STS on the migration and tube formation of HUVECs during pyroptosis was examined using a cell scratch test and a matrix gel tube formation test. The expressions of NLRP3, caspase-1, interleukin-18, and interleukin-1β were detected using RT-PCR and Western blotting. Repeated measures ANOVA was used to compare the concentrations at different time points, t-tests were used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. P<0.05 was considered statistically significant. Results:STS below 50.00 μg/ml had no effect on the proliferation of HUVECs, while 500.00 μmol/L H 2O 2 had the most significant effect on inducing pyroptosis in HUVECs. TUNEL staining showed that compared with the control group, the number of TUNEL-positive cells in H 2O 2 group was significantly increased, and the difference was statistically significant ( P<0.01). However, there was no significant difference in the number of TUNEL-positive cells in the H 2O 2+ STS group ( P>0.05). The results of ROS detection showed that compared with the H 2O 2 group, intracellular ROS levels in the H 2O 2+ STS group was significantly decreased, and the difference was statistically significant ( P<0.01). Cell scratch and tube formation in vitro experiments showed that compared with the control group, cell mobility and tube formation ability were significantly decreased in the H 2O 2 group (all P<0.01), and there was no statistical significance in the H 2O 2+ STS group (all P>0.05). RT-PCR and Western blotting results showed that, compared with the H 2O 2 group, the expression of pyroptosis-related factors in the H 2O 2+ STS group was significantly decreased (all P<0.05). Conclusion:STS can inhibit the excessive production of ROS, promote the cell migration and tubular formation of HUVECs after pyroptosis induction, and alleviate H 2O 2-induced pyroptosis of HUVECs, thereby promoting angiogenesis.

Multiple myeloma (MM) is a malignant disease caused by the abnormal clonal proliferation of plasma cells, accounting for 10% of all hematologic cancers. In recent years, with the development and application of targeted drugs, a significant progress has been observed in the treatment methods of MM, but patients still face the challenges of relapse and drug resistance. Moreover, G protein-coupled receptor class C Group 5 member D (GPRC5D) is highly expressed in MM cells independently of B cell maturation antigen (BCMA) and is a highly promising target following BCMA. Aside from emphasizing the therapeutic efficacy and safety of targeting GPRC5D for the treatment of MM, this study also provides a prospective view on the mechanisms of drug resistance and relapse associated with GPRC5D-targeted therapies, as well as the timing of sequential or combined treatment strategies involving the dual targeting of both GPRC5D and BCMA.

Background There is a lack of research evidence on the association between sugar-sweetened beverage (SSB) consumption and gestational diabetes mellitus (GDM) in China. Objective To explore the association between frequency of SSB consumption before pregnancy and risk of GDM in pregnant women in Shaanxi Province, and to provide a scientific basis for targeted interventions to control maternal blood glucose. Methods The recruitment to the China Birth Cohort study started in October 2020. Pregnant women at 6-16 weeks who had their first prenatal examination at five hospitals in Shaanxi Province were recruited. A maternal health questionnaire was used to collect basic information about pregnant women. A semi-quantitative food frequency questionnaire was used to collect the consumption of carbonated beverages, fruit and vegetable juice beverages, coffee beverages, and milk tea beverages in one year before pregnancy, which were summed to obtain the SSB consumption. Pregnant women were divided into three groups according to SSB consumption, namely <1 serving·week⁻¹, 1-4 servings·week⁻¹, and ≥5 servings·week⁻¹. GDM was confirmed by oral glucose tolerance test (OGTT) between 24-28 weeks of gestation. A binary logistic regression model was applied to explore the association between SSB consumption and risk of GDM. Multiple linear regression was applied to investigate the associations between SSB consumption (per 1-serving·d⁻¹ increase) and OGTT fasting plasma glucose, 1-hour glucose, and 2-hour glucose. Results A total of 3811 pregnant women were finally enrolled in this study, of which 752 developed GDM, with an incidence rate of 19.7%. The incidence rates of GDM in pregnant women with SSB consumption frequency of <1 serving·week⁻¹, 1-4 servings·week⁻¹, and ≥5 servings·week⁻¹ were 18.0%, 21.1%, and 26.8%, respectively. After adjusting for maternal age, pre-pregnancy body mass index (BMI), education, number of children born, family history of diabetes, smoking, alcohol consumption, physical activity level, and total energy intake, the risk of GDM increased by 26% (OR=1.26, 95%CI: 1.05, 1.50) in the 1-4 servings·week⁻¹ group and by 76% (OR=1.76, 95%CI: 1.31, 2.38) in the ≥5 servings·week⁻¹ group compared to the <1 serving·week⁻¹ SSB consumption group, respectively. Further stratified analysis revealed no interaction effect (P_interaction>0.05) between SSB consumption and maternal age, pre-pregnancy BMI, or first labor or not. For each additional SSB consumption per day, the risk of GDM increased by 94% (OR=1.94, 95%CI: 1.37, 2.75); and the maternal OGTT 1-hour glucose and 2-hour glucose increased by 0.33 mmol·L⁻¹ and 0.18 mmol·L⁻¹, respectively (P<0.05), and no significant increase in fasting plasma glucose was found (P>0.05). Conclusion Higher SSB consumption before pregnancy increases the risk of GDM in pregnant women.