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The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia

  • Lei Yang , YaMing Liu , Qiao Guo and DePeng Jiang EMAIL logo
Published/Copyright: August 30, 2023
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Open Medicine
From the journal Open Medicine Volume 18 Issue 1

Abstract

It is of urgent need to understand the safety and effectiveness of novel coronavirus (COVID-19)-inactivated vaccine in patients with hyperlipidemia (HLD). However, data on the safety and immune response of SARS-CoV-2-inactivated vaccine in HLD patients are limited. In this prospective study, 105 patients with HLD and 74 healthy controls (HCs) were selected. Within 16–168 days after inoculation-inactivated vaccine, the anti-receptor-binding domain (RBD) IgG and SARS-CoV-2 neutralizing antibodies (NAbs) were evaluated, respectively. Flow cytometry was performed to evaluate RBD-specific B cells and memory B cells. There was no significant difference between HLD patients and HCs in adverse events (AEs) within 7 days after vaccination, and no serious AEs occurred. The seropositivity rates and titers of two Abs (anti-RBD IgG and CoV-2 NAbs) were lower in HLD patients than in HCs (all, p < 0.05). HLD showed significantly lower frequencies of RBD-specific B cells than HCs (p = 0.040). However, in high cholesterol, high triglyceride, mixed (MiX), and lipid control (HC) subgroups, there was no significant difference in the seropositivity rates and titers of the both Abs. Through mixed factor analysis shows that days between the second dose and sample collection/antibody measurement were associated with the lower anti-RBD IgG antibody levels. In conclusion, inactivated COVID-19 vaccine is safe and well tolerated for HLD patients, but the humoral immune may be limited.

Keywords: COVID-19 vaccine; safety; effectiveness; hyperlipidemia

1 Introduction

According to the World Health Organization, new coronavirus has wreaked havoc since it first appeared in 2019, causing more than 600 million infections and more than 6 million deaths worldwide as of October 2022. The current novel coronavirus (COVID-19) vaccination remains an effective measure to prevent infection and severe disease, which heavily depends on the production of Abs to SARS-CoV-2 and a sustained immune response. Previous studies have shown that patients with hyperlipidemia (HLD) may increase the incidence of COVID-19 infection and mortality from severe disease [1,2]. The greatest ever study on cholesterol levels was published in the journal Nature in 2020, and it revealed that the Chinese population’s cholesterol levels, which may have increased from the lowest in the world, were the highest in the globe, surpassed a number of high-income Western nations [3]. Along with the country’s expanding economy, rising standard of living, and altering lifestyles, the prevalence of HLD is rising quickly in China [4].

According to previous studies, obesity is one of the most common risk factors for thromboembolic events after COVID-19 vaccination [5]; yet, obese patients are often associated with HLD [6]. For the purpose of evaluating the safety of the inactivated COVID-19 vaccine in patients with HLD, we recorded adverse events (AEs) in these patients within 7 days following the immunization.

Although some research have indicated that obesity is not related with an Ab response [7,8], many prior studies [9,10] have demonstrated that obese patients have a low Ab response to the COVID-19 vaccination and the majority of obese patients have impaired lipid metabolism. It is unknown in China whether patients with HLD can produce a potent immune response following an inactivated COVID-19 immunization. Therefore, after administering the COVID-19 vaccine to HLD patients, we evaluated the seropositivity rates and titers of the Abs that were created.

Following vaccination, B-cell immunity plays a major role in the generation of particular Abs. Memory B cells (MBCs), which quickly proliferate and differentiate into antibody-secreting cells when reinfection occurs, mediate persistent humoral immunity [11,12]; this prevents the onset of serious illness or death. The importance of B-cell levels in HLD after vaccination with the COVID-19 vaccine, however, has not yet been studied in detail.

To evaluate the safety and Abs’ response of COVID-19-inactivated vaccine, 105 patients with HLD and 74 healthy controls (HCs) were enrolled in the study. MBCs and receptor-binding domain (RBD)-specific B cells were found using flow cytometry.

2 Materials and methods

2.1 Population and study design

From May 2021 to December 2021, all participants were enrolled in the study at the Second Hospital Associated with Chongqing Medical University. Inclusion standards was as follows: (1) hypercholesterolemia, which is defined as an elevated serum total cholesterol level greater than 572 mmol/L and a normal triglyceride level, or triglycerides less than 170 mmol/L; (2) hypertriglyceridemia: elevated blood triglyceride levels over 1.70 mmol/L in the presence of normal total cholesterol levels, or total cholesterol less than 572 mmol/L; (3) increased blood total cholesterol and triglyceride levels, or total cholesterol above 572 mmol/L and triglycerides over 170 mmol/L, are indicative of mixed hyperlipidemia; and (4) lipid control: participants with triglycerides and total cholesterol under 170 and 572 mmol/L, respectively, after lipid-lowering medication or exercise. Exclusion criteria include the following: (1) no more than one dose of the COVID-19 vaccine (BBIBP-CorV or Corona Vac), (2) age <18 years, (3) a history of SARS-CoV-2 infection, (4) the presence of immunosuppression or immunosuppression within 6 months, and (5) the presence of persistent pregnancy.

This study was approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University and conformed with the ethical guidelines of the Declaration of Helsinki. Written informed consent was obtained from all participants prior to their inclusion in the study. This study has been registered at ClinicalTrials.gov (NCT05043246).

2.2 AEs

A questionnaire was used to gauge AEs 7 days following the vaccine. The Chinese Medical and Drug Administration’s scale was then used to classify all AEs (2019 version).

2.3 Abs’ detection

Using the fully automated chemiluminescence assay MAGLUMI 2000, we examined all plasma samples for S-RBD IgG antibody (anti-S-RBD IgG) and SARS-CoV-2 neutralizing antibodies (NAbs) (Snibe, Shenzhen, China). The kit’s instructions state that CoV-2 NAbs and anti-RBD IgG threshold values of >0.15 μg/mL and >1 AU/mL, respectively, are required for seropositivity, while a value of less than or equal to the threshold is required for seronegative status.

2.4 RBD+-specific B-cell assay

Fresh peripheral blood samples were collected and centrifuged through a Ficoll density gradient (Histopaque; Sigma-Aldrich Corporation, St Louis, MO, USA). Brilliant Violet 421™ Streptavidin-conjugated Abs (BioLegend, San Diego, CA, USA) and biotinylated Abs against the RBD of the SARS-CoV-2 spike protein (Sino Biological, Beijing, China) at a molar ratio of 1:4 were used for identification of the MBCs. For flow cytometry (Beckman Coulter, Inc., Brea, CA, USA), the cells were washed with phosphate-buffered saline, suspended staining buffer containing 2% fetal bovine serum, and probed with Abs against IgG, IgM, cluster of differentiation 3 (CD3), CD19, CD21, and CD27 (all, Biolegend). The data were examined using FlowJo software (version 10.0.7; FlowJo, LLC, Ashland, OR, USA). The cell percentages were calculated for just MBCs, include RBD-specific B cell (CD3− CD19+ RBD+), RBD-specific MBCs (CD3− CD19+ RBD+ CD27+), RBD+ atypical MBCs (CD3− CD19+ RBD+ CD21− CD27−), RBD+-activated MBCs (CD3− CD19+ RBD+ CD21− CD27+), RBD+-resting MBC (CD3− CD19+ RBD+ CD21+ CD27+), and RBD+ intermediate MBC (CD3− CD19+ RBD+ CD21 + CD27−).

2.5 Statistical analysis

Chi-square and Fisher’s exact tests were applied to categorical variables, while Mann–Whitney U test was applied to continuous variables with normally distributed or non-normal distribution, respectively. The Kruskal–Wallis test was used to compare three or more groups, and Bonferroni was employed to correct the outcomes of multiple comparisons. Using univariate and multivariate ordinal logistic regression analyses, the variables that significantly affected Abs were found. A statistical study was performed utilizing IBM SPSS (version 26.0). GraphPad Prism (version 9.2.0) was used for the plotting. The threshold for statistical significance was a p value of 0.05.

3 Results

As shown in Table 1, for HLD patients and HCs, no significant differences in median age, percentage of males, mean body mass index (BMI), vaccine type, median number of days after the second vaccination, results of routine blood tests (red blood cell, white blood cells, hemoglobin, and platelets), but mean BMI and lymphocyte were higher in HLD patients than in HCs.

Table 1

Characteristics of participants after two-dose vaccination

HLD patients (n = 105) HCs (n = 74) P
Age (years) 59 (19–89) 61 (19–87) 0.814
Gender
Male, n (%) 50.5% (53/105) 55.4% (41/74) 0.515
Female, n (%) 49.5% (52/105) 44.6% (33/74)
BMI# (kg/m2) 24.72 (19.28–48.83) 23.20 (13.60–33.98) 0.027
Vaccine type
Corona 68.6% (72/105) 66.2% (49/74) 0.740
BBIBP-CorV 31.4% (33/105) 33.8% (25/74)
Days between second dose and sample collection/antibody measurement, median (range) 50 (16–159) 41 (20–168) 0.239
Red blood cell# (1012/L) 4.47 (2.37–5.66) 4.46 (2.46–6.50) 0.789
Hemoglobin# (g/L) 137 (71–171) 137 (73–179) 0.924
White blood cell# (109/L) 6.37 (2.67–15.44) 6.09 (3.11–11.47) 0.101
Lymphocyte# (109/L) 1.69 (0.45–5.91) 1.55 (0.21–2.70) 0.029
Platelet# (109/L) 199 (101–366) 205 (94–420) 0.846

Lists the participant characteristics after the full vaccination cycle. Fisher’s exact test and the Chi-Square statistic test were applied to categorical variables, while the Mann-Whitney U test was applied to continuous variables. At p < 0.05, statistics were deemed significant.

#Shown as the median (range).

As can be shown in Table 2, there were no appreciable differences in the AEs that occurred 7 days following COVID-19 vaccination between HLD patients and HCs.

Table 2

AEs of COVID-19 vaccination in participants

Variable HLD patients (n = 105) HCs (n = 74) P
Overall AEs within 7 days 13.3% (14/105) 9.5% (7/74) 0.428
Local AEs 7.6% (8/105) 4.1% (3/74) 0.508
Systemic AEs 5.7% (6/105) 5.4% (4/74) 1.000
Grade 3 and 4 AEs / / /

Data are expressed as n (%) and the chi-square test was used to compare the statistical differences between the two groups.

3.1 Humoral immune response to inactivated SARS-CoV-2 vaccines in HLD patients

As shown in Figure 1, seropositivity rates (68.9% vs 91.9%, p < 0.001, 64.2% vs 85.1%, p = 0.002) and titers (median [interquartile range (IQR)]: 2.24 [0.67–5.30] vs 3.35 [1.83–6.05], p = 0.026, 0.19 [0.12–0.32] vs 0.24 [0.19–0.43], p = 0.002) for the both Abs (anti-RBD IgG and CoV-2 NAbs) were lower in HLD patients than in HCs.

Figure 1 Antibodies response to inactivated SARS-CoV-2 vaccines in HLD patients. (a and b) The seropositivity rates and titers of anti-RBD IgG in HLD patients. (c and d) The seropositivity rates and titers of CoV-2 NAbs in HLD patients. The Chi-square test and Mann–Whitney U test were used for comparison.
Figure 1

Antibodies response to inactivated SARS-CoV-2 vaccines in HLD patients. (a and b) The seropositivity rates and titers of anti-RBD IgG in HLD patients. (c and d) The seropositivity rates and titers of CoV-2 NAbs in HLD patients. The Chi-square test and Mann–Whitney U test were used for comparison.

In contrast to HCs, HLD patients had reduced frequencies of RBD-specific B cells (mean [95% confidence interval (CI)]: 18.88 [17.79–19.94] vs 20.63 [17.31–23.35], p = 0.040), as shown in Figure 2. The frequencies of RBD+-resting MBCs, RBD+-activated MBCs, RBD+ atypical MBCs, RBD+ intermediate MBCs, and RBD+-specific MBCs were similar in HLD patients and HCs.

Figure 2 MBC response to inactivated SARS-CoV-2 vaccines in HLD patients. (a–f) The frequencies of RBD-specific B cells, RBD+-resting MBCs, RBD+-activated MBCs, RBD+ atypical MBCs, RBD+ intermediate MBCs, and RBD+-specific MBCs in HLD patients, and the Mann–Whitney U test was used for comparison.
Figure 2

MBC response to inactivated SARS-CoV-2 vaccines in HLD patients. (a–f) The frequencies of RBD-specific B cells, RBD+-resting MBCs, RBD+-activated MBCs, RBD+ atypical MBCs, RBD+ intermediate MBCs, and RBD+-specific MBCs in HLD patients, and the Mann–Whitney U test was used for comparison.

3.2 Humoral immune response to inactivated SARS-CoV-2 vaccines in HLD subgroups

Figure 3 illustrates the seropositivity rates and titers of the both Abs among in H-CL, H-TG, MiX, and HC. Seropositivity rates (66.7% vs 60.0% vs 73.3% vs 82.4%, p = 0.361, 61.1% vs 57.5% vs 63.3% vs 82.4%, p = 0.350) and titers (2.99 [0.80–9.68] vs 1.66 [0.57–4.56] vs 2.45 [0.85–6.13] vs 3.45 [2.01–4.60], p = 0.244, 0.24 [0.18–0.40] vs 0.17 [0.11–0.30] vs 0.20 [0.12–0.35] vs 0.25 [0.18–0.31], p = 0.360) of the both Abs were not significantly different among these groups.

Figure 3 Antibodies response to inactivated SARS-CoV-2 vaccines in HLD subgroups. (a and b) The seropositivity rates and titers of anti-RBD IgG in the hyperlipidemic group (H-CL), high triglyceride group (H-TG), mixed group (MiX), and lipid control group (HC). (c and d) The seropositivity rates and titers of CoV-2 NAbs in the hyperlipidemic group (H-CL), high triglyceride group (H-TG), mixed group (MiX), and lipid control group (HC). The Chi-square test and Kruskal–Wallis test were used for comparison.
Figure 3

Antibodies response to inactivated SARS-CoV-2 vaccines in HLD subgroups. (a and b) The seropositivity rates and titers of anti-RBD IgG in the hyperlipidemic group (H-CL), high triglyceride group (H-TG), mixed group (MiX), and lipid control group (HC). (c and d) The seropositivity rates and titers of CoV-2 NAbs in the hyperlipidemic group (H-CL), high triglyceride group (H-TG), mixed group (MiX), and lipid control group (HC). The Chi-square test and Kruskal–Wallis test were used for comparison.

As shown in Figure 4, the frequencies of RBD-specific B cells, RBD+-resting MBCs, RBD+ atypical MBCs, RBD+ intermediate MBCs, and RBD+-specific MBCs were not significantly different among the H-CL, H-TG, MiX, and HC. Only RBD+-activated MBC (20.30 [14.73–32.38] vs 24.75 [18.00–37.03] vs 17.90 [13.83–26.03] vs 16.00 [11.05–24.96], p = 0.037) differed among the four groups.

Figure 4 MBCs’ response to inactivated SARS-CoV-2 vaccines in HLD subgroups. (a–f) The frequencies of RBD-specific B cells, RBD+-resting MBCs, RBD+-activated MBCs, RBD+ atypical MBCs, RBD+ intermediate MBCs, and RBD+-specific MBCs in the high cholesterol group (H-CL), high triglyceride group (H-TG), mixed group (MiX), and lipid control (HC). The Kruskal–Wallis test was used for comparison, and the Bonferroni test was used to rectify it.
Figure 4

MBCs’ response to inactivated SARS-CoV-2 vaccines in HLD subgroups. (a–f) The frequencies of RBD-specific B cells, RBD+-resting MBCs, RBD+-activated MBCs, RBD+ atypical MBCs, RBD+ intermediate MBCs, and RBD+-specific MBCs in the high cholesterol group (H-CL), high triglyceride group (H-TG), mixed group (MiX), and lipid control (HC). The Kruskal–Wallis test was used for comparison, and the Bonferroni test was used to rectify it.

3.3 Humoral immune response to inactivated SARS-CoV-2 vaccines in HLD patients aged ≥65 or <65 years

According to Figure 5, there were no significant differences in seropositivity rates (71.4% vs 66.7%, p = 0.607, 69% vs 60.3%, p = 0.362) and titers (median [IQR]: 2.46 [0.84–6.82] vs 2.24 [0.60–4.63], p = 0.282, 0.21 [0.11–0.34] vs 0.18 [0.12–0.32], p = 0.598) for both Abs in HLD patients aged ≥65 or <65 years.

Figure 5 Antibodies’ response to inactivated SARS-CoV-2 vaccines in HLD patients aged ≥65 or <65 years. (a and b) The seropositivity rates and titers of anti-RBD IgG for HLD patients aged ≥65 or <65 years. (c and d) The seropositivity rates and titers of CoV-2 NAbs for those aged ≥65 or <65 years. The Chi-square test and Mann–Whitney U test were used for comparison.
Figure 5

Antibodies’ response to inactivated SARS-CoV-2 vaccines in HLD patients aged ≥65 or <65 years. (a and b) The seropositivity rates and titers of anti-RBD IgG for HLD patients aged ≥65 or <65 years. (c and d) The seropositivity rates and titers of CoV-2 NAbs for those aged ≥65 or <65 years. The Chi-square test and Mann–Whitney U test were used for comparison.

As shown in Figure 6, the frequencies of RBD+-resting MBCs and RBD+ intermediate MBCs were lower in HLD patients aged ≥65 years than in <60 years (median [IQR]: 17.00 [11.33–20.43] vs 11.27 [1.21–18.60], p = 0.011, 32.40 [20.48–38.38] vs 20.00 [1.72–33.90], p = 0.009). In contrast, there were no significant differences in RBD-specific B cells, RBD+ atypical MBCs, RBD+-activated MBCs, and RBD+-specific MBCs.

Figure 6 MBCs’ response to inactivated SARS-CoV-2 vaccines in HLD patients aged ≥65 or <65 years. (a–f) The frequencies of RBD-specific B cells, RBD+-resting MBCs, RBD+-activated MBCs, RBD+ atypical MBCs, RBD+ intermediate MBCs, and RBD+-specific MBCs in HLD patients aged ≥65 or <65 years, and the Mann–Whitney U test was used for comparison.
Figure 6

MBCs’ response to inactivated SARS-CoV-2 vaccines in HLD patients aged ≥65 or <65 years. (a–f) The frequencies of RBD-specific B cells, RBD+-resting MBCs, RBD+-activated MBCs, RBD+ atypical MBCs, RBD+ intermediate MBCs, and RBD+-specific MBCs in HLD patients aged ≥65 or <65 years, and the Mann–Whitney U test was used for comparison.

As shown in Tables 3 and 4, we found that days between the second dose and sample collection/antibody measurement were associated with lower anti-RBD IgG Ab levels through univariate and multivariate linear regression analyses.

Table 3

Univariate and multifactorial analyses of anti-RBD IgG in HLD patients

Univariate OR (95% CI) P Multivariate OR (95% CI) P
Gender (female) 0.659 (0.283, 1.507) 0.326 1.198 (0.224, 0.698) 0.833
Age (years) 1.015 (0.987, 1.044) 0.308 1.022 (0.954, 1.072) 0.704
BMI (kg/m2) 0.993 (0.889, 1.120) 0.900 0.967 (0.824, 1.146) 0.663
Vaccine tape (Corona Vac) 1.690 (0.703, 4.029) 0.236 1.536 (0.346, 6.881) 0.567
Days between second dose and sample collection/antibody measurement 0.969 (0.954, 0.983) <0.001 0.975 (0.950, 0.996) 0.032
Red blood cell (1012/L) 0.879 (0.393, 1.913) 0.746
White blood cell (109/L) 0.937 (0.753, 1.168) 0.551
Hemoglobin (g/L) 1.006 (0.980, 1.033) 0.638
Lymphocyte (109/L) 1.129 (0.623, 2.244) 0.704
Platelet (109/L) 1.000 (0.992, 1.008) 0.985
Cholesterol (mmol/L) 1.115 (0.745, 1.705) 0.601 1.161 (0.684, 2.008) 0.572
Triglyceride (mmol/L) 1.132 (0.818, 1.659) 0.481 1.022 (0.590, 1.967) 0.940
RBD-specific B cells (%) 1.008 (0.936, 1.088) 0.832 1.032 (0.896, 1.192) 0.654
RBD+-resting MBC (%) 1.033 (0.993, 1.080) 0.123 0.517 (1.187, 1.723) 0.930
RBD+-activated MBC (%) 0.983 (0.954, 1.012) 0.241 0.475 (0.106, 1.587) 0.921
RBD+ atypical MBC (%) 0.987 (0.965, 1.009) 0.246 0.103 (0.028, 2.879) 0.760
RBD+ intermediate MBC (%) 1.015 (0.991, 1.040) 0.230 0.101 (0.027, 2.853) 0.759
RBD-specific MBC (%) 1.000 (0.972, 1.030) 0.999 0.214 (0.088, 3.729) 0.300

CI, confidence interval, OR, odds ratio, RBD, receptor-binding domain, MBC, memory B cell.

4 Discussion

In this prospective trial, we assessed the inactivated SARS-CoV-2 vaccine’s safety, Ab responses, RBD-specific B cells, and MBCs in HLD patients and HCs. Our findings demonstrate that the inactivated vaccination is safe and well tolerated in HLD patients but reduced the titers of Abs and the frequencies of RBD-specific B cell.

Table 4

Univariate and multifactorial analysis of CoV-2 NAbs in HLD patients

Univariate OR (95% CI) P Multivariate OR (95% CI) P
Gender (female) 0.626 (0.278, 1.392) 0.254 0.720 (0.156, 3.330) 0.669
Age (years) 1.015 (0.987, 1.043) 0.296 0.994 (0.942, 1.046) 0.807
BMI (kg/m2) 1.006 (0.903, 1.133) 0.913 1.029 (0.887, 1.205) 0.694
Vaccine tape (Corona Vac) 1.775 (0.759, 4.154) 0.183 1.515 (0.395, 5.827) 0.540
Days between second dose and sample collection/antibody measurement 0.977 (0.963, 0.989) <0.001 0.984 (0.962, 1.004) 0.136
Red blood cell (1012/L) 1.213 (0.570, 2.608) 0.614
White blood cell (109/L) 0.940 (0.759, 1.164) 0.566
Hemoglobin (g/L) 1.015 (0.990, 1.043) 0.242
Lymphocyte (109/L) 0.895 (0.498, 1.624) 0.702
Platelet (109/L) 1.001 (0.994, 1.009) 0.768
Cholesterol (mmol/L) 1.138 (0.780, 1.696) 0.507 1.141 (0.702, 1.906) 0.594
Triglyceride (mmol/L) 1.012 (0.743, 1.409) 0.939 1.276 (0.742, 2.587) 0.432
RBD-specific B cells (%) 1.007 (0.937, 1.083) 0.857 1.046 (0.925, 1.193) 0.475
RBD+-resting MBC (%) 1.042 (1.002, 1.089) 0.051 0.485 (0.117, 1.550) 0.910
RBD+-activated MBC (%) 0.978 (0.948, 1.006) 0.125 0.452 (0.106, 1.455) 0.902
RBD+ atypical MBC (%) 0.977 (0.955, 0.999) 0.043 0.536 (0.156, 1.652) 0.922
RBD+ intermediate MBC (%) 1.027 (1.003, 1.052) 0.031 0.540 (0.157, 1.684) 0.923
RBD-specific MBC (%) 0.999 (0.972, 1.028) 0.971 1.173 (0.074, 1.919) 0.907

CI, confidence interval, OR, odds ratio, RBD, receptor-binding domain, MBC, memory B cell.

COVID-19 patients with dyslipidemia may worsen mortality and severity [1,2,13], hence prompt administration of the inactivated vaccine may be advantageous in this population of patients. Limited registration trials have been conducted, nonetheless, on the humoral immune response and safety of the inactivated SARS-CoV-2 vaccination in individuals with HCs. The overall incidence of AEs within 7 days of vaccination with the COVID-19 vaccine in HLD patients was reported to be 13.3%, comparable to HCs (9.5%), when we initially evaluated the safety of inactivated vaccine in HLD patients, but lower than in phase 3 trials of the Turkish [14] Corona vaccine (18.9%) and phase 1/2 studies of the Chinese [15] BBIBP-CorV (23–29%). The HLD patients and HCs experienced similar local AEs (7.6% vs 4.1%) and overall AEs (5.7% vs 5.4%), and no significant AEs (grade 3/4 AEs) occurred in any of the participants.

Our results showed that the titers of both Abs were lower in HLD patients than in HCs 16–168 days after vaccination; previous study has demonstrated that Ab levels are lower in obese patients than in healthy groups after vaccination [7,8,16], and this study’s HLD patients’ BMI was also higher than that of HCs. Obesity is strongly associated with HLD. Patients with HLD also had reduced seroconversion rates for both Abs, at 68.6 and 63.5%, respectively. However, by mixed factors analysis, no correlation was found between Ab titers and lipid or cholesterol concentrations. The reason may be that the overall vaccination time of this patient cohort is longer or immunogenicity itself is lower.

Our findings revealed that the frequencies of RBD-specific B cells were lower in HLD patients than in HCs, and prior research revealed that the frequencies of RBD-specific B cells were significantly lower in some patients with chronic disease 1 month after receiving the inactivated COVID-19 vaccine [17]. These findings suggested that humoral immunity in HLD patients may be compromised after receiving the SARS-CoV-2 vaccine.

In our result that we found the frequencies of RBD+-activated MBCs were lower in lipid control group than in high triglyceride group, but not for other MBCs, may be due to the MBCs were resting or intermediate status in lipid control group.

Similar to the findings of some earlier studies [18,19,20], we used mixed factor analysis to again identify days between the second dose and sample collection/antibody measurement as a risk factor for anti-RBD IgG Abs’ responses. This suggests the need for monitoring the Ab levels and booster dose in time. Contrary to the findings of earlier research [21,22,23], etc., age and gender were not related to Ab levels in our investigation. This analysis may have been necessary because of the study’s limited sample size, which has to be further confirmed by further trials with a larger sample size.

There are some flaws in the current study. First of all, this study was conducted in a single center with a modestly sized sample. Second, the T cells were not analyzed in the study. Third, there were no longitudinal analyses; only cross-sectional comparisons were made. But this research has certain advantages as well: For the first time, the safety and immunogenicity of COVID-19 vaccine for patients with hyperlipemia have been clarified and helped doctors respond to patient concerns. As for safety, Ab response, RBD-specific B cells, and MBCs, this study gives an adequate evaluation of all of these factors. Third, days between the second dose and sample collection/antibody measurement were found to be a risk factor for anti-RBD IgG Ab levels, meaning that Ab levels dropped with time.

In conclusion, patients with HLD tolerated the SARS-CoV-2-inactivated vaccine well and without any severe AEs, but the humoral immune may be limited.

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  1. Funding information: This work is supported by the National Science and Technology Major Project of China (2017ZX10202203-007, 2017ZX10202203-008, 2018ZX10302206-003) and a pilot project of clinical cooperation between traditional Chinese and western medicine for significant and complicated diseases of National Administration of Traditional Chinese Medicine: hepatic fibrosis. We also acknowledge the support of the National Natural Science Foundation of China (81772198), the Natural Science Foundation of Chongqing, China (cstc2020jcyj-msxmX0389), and the Kuanren Talents Program of the second affiliated Hospital of Chongqing Medical University.

  2. Author contributions: Concept and design: DePeng Jiang; funding acquisition: Hong Ren and DePeng Jiang; participant recruitment and characterization: Lei Yang, DePeng Jiang; experiment execution: Lei Yang; acquisition, analysis or interpretation of data: Lei Yang, DePeng Jiang; supervision: DePeng Jiang; administrative support: Hong Ren; drafting and critical revi-sion of manuscript: LeiYang, YaMing Liu, Qiao Guo, DePeng Jiang. All authors contributed to the article and approved the submitted version.

  3. Conflict of interest: The authors declare no conflict of interest.

  4. Data availability statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Appendix

Figure A1 Full gating strategy of flow cytometry for target cell population.
Figure A1

Full gating strategy of flow cytometry for target cell population.

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Received: 2023-01-06
Revised: 2023-07-27
Accepted: 2023-07-31
Published Online: 2023-08-30

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0780
Keywords for this article
COVID-19 vaccine; safety; effectiveness; hyperlipidemia
Creative Commons
BY 4.0

Articles in the same Issue

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  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
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  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
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  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
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  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
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  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
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  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
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  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
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  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
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  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
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  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
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  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
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  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
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  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
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  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
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  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
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  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
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  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
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  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
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  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
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  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
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  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
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  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
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  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
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  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
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  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
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  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
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  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
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  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
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  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
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  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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