Numerical evaluation of spinal reconstruction using a 3D printed vertebral body replacement implant: effects of material anisotropy.

Background and objective: Artificial vertebral implants have been widely used for functional reconstruction of vertebral defects caused by tumors or trauma. However, the evaluation of their biomechanical properties often neglects the influence of material anisotropy derived from the host bone and implant's microstructures. Hence, this study aims to investigate the effect of material anisotropy on the safety and stability of vertebral reconstruction. Material and methods: Two finite element models were developed to reflect the difference of material properties between linear elastic isotropy and nonlinear anisotropy. Their biomechanical evaluation was carried out under different load conditions including flexion, extension, lateral bending and axial rotation. These performances of two models with respect to safety and stability were analyzed and compared quantitatively based on the predicted von Mises stress, displacement and effective strain. Results: The maximum von Mises stress of each component in both models was lower than the yield strength of respective material, while the predicted results of nonlinear anisotropic model were generally below to those of the linear elastic isotropic model. Furthermore, the maximum von Mises stress of natural vertebra and reconstructed system was decreased by 2-37 MPa and 20-61 MPa, respectively. The maximum reductions for the translation displacement of the artificial vertebral body implant and motion range of whole model were reached to 0.26 mm and 0.77°. The percentage of effective strain elements on the superior and inferior endplates adjacent to implant was diminished by up to 19.7% and 23.1%, respectively. Conclusion: After comprehensive comparison, these results indicated that the finite element model with the assumption of linear elastic isotropy may underestimate the safety of the reconstruction system, while misdiagnose higher stability by overestimating the range of motion and bone growth capability.

[Bone Metabolism of Multiple Myeloma Bone Disease Patients with Different Blood Separation Results].

OBJECTIVE: To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma (MM) bone disease (MBD) patients with different blood separation results. METHODS: A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group [119 cases, serum, colloid and red blood cell (RBC) from top to bottom of sample] and abnormal group (15 cases, serum, mixed layer of RBC and serum, colloid and RBC from top to bottom of sample) according to the results of blood separation. According to the imaging findings, MBD was classified into grade 0-4, grade 0-2 was mild, and grade 3-4 was severe. The MBD grade of patients in the two groups was analyzed. The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated. The correlation between ß2-microglobulin (MG) and bone metabolic indexes was analyzed by Pearson correlation analysis. RESULTS: In the control group, there were 69 cases of grade 0-2 and 50 cases of grade 3-4, while in the abnormal group, there were 5 cases of grade 0-2 and 10 cases of grade 3-4, the difference was statistically significant (P < 0.05). The serum ß2-MG, ß-CTX levels in abnormal group were both significantly higher than those in control group, while the levels of P1NP and osteocalcin (OC) were significantly lower (all P < 0.001). In the control group, there were 95 patients with ≥ partial response (PR) and the blood separation results were not changed, while 24 patients with 0.05). Compared with before treatment, the levels of ß-CTX and ß2-MG in the control group with unchanged blood separation results were significantly decreased (both P < 0.001), while the levels of P1NP and OC were significantly increased (P < 0.01, P < 0.001), and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change (P >0.05); the levels of ß-CTX and ß2-MG in the abnormal group transformed to normal blood separation result were significantly decreased (both P < 0.01), while the levels of P1NP and OC were significantly increased (P < 0.001, P < 0.01), and the level of each index in patients with unchanged blood separation results did not significantly change (P>0.05). Pearson correlation analysis showed that serum ß2-MG was positively correlated with ß-CTX (r =0.709, P < 0.001), and negatively correlated with P1NP and OC (r =-0.410,r =-0.412, both P < 0.001). CONCLUSION: MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis, which is closely related to the significant increase of bone resorption index ß-CTX level and decrease of bone formation index P1NP and OC levels, leading to more serious bone metabolic homeostasis disorder. The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition, efficacy monitoring and prognosis evaluation of MBD patients.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

[The Role of NK Cells in Allogeneic Hematopoietic Stem Cell Micro-Transplantation for Acute Myeloid leukemia].

OBJECTIVE: To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST) in the treatment of patients with acute myeloid leukemia(AML). METHODS: Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed. The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor (GPBSC), followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission (CR). The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated. Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype, including KIR ligand mismatch, 2DS1, haplotype, and HLA-Cw ligands on survival prognosis of patients. RESULTS: Forty-two patients received MST induction therapy, and the CR rate was 57.1% after 1 course and 73.7% after 2 courses. Multivariate analysis showed that, medium and high doses of NK cells was significantly associated with improved disease-free survival (DFS) of patients (HR=0.27, P =0.005; HR=0.21, P =0.001), and high doses of NK cells was significantly associated with improved overall survival (OS) of patients (HR=0.15, P =0.000). Donor 2DS1 positive significantly increases OS of patients (HR=0.25, P =0.011). For high-risk patients under 60 years old, patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group (P =0.036); donor 2DS1 positive significantly prolonged OS of patients (P =0.009). CONCLUSION: NK cell dose, KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST, improve the survival of AML patients.

Association between ambient particulate matter exposure and mitochondrial DNA copy number: A systematic review and meta-analysis.

BACKGROUND: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results. METHODS: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated. RESULTS: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM2.5 (ß = -0.084, 95 % CI: -0.521, 0.353; I2 = 93 %) and PM10 (ß = 0.035, 95 % CI: -0.129, 0.199; I2 = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM2.5 (ß = 0.023, 95 % CI: -0.087, 0.133; I2 = 0 %) and PM10 (ß = 0.006, 95 % CI: -0.135; 0.147; I2 = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate." CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings.

Effect of Methyl Hydro-Silicone Oil Content and Aging Time on Compression Modulus and Breakdown Strength of Additional Liquid Silicone Rubber Gel.

The performance of silicone rubber gel elastomers is affected by the composition and structure of the crosslinker. In this work, a two-component addition liquid silicone rubber gel material was developed, and the effects of the contents of two methyl hydro-silicone oils on the compression modulus and breakdown strength of the silicone rubber gel insulating material, as well as the performance change after hot air aging at different times (24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h), were studied. The results showed that the breakdown strength and compression modulus exhibited an upward trend with the increase in the hydrogen silicone oil content. The best performance was achieved in the silicone rubber gel with Si-H:Si-Vi = 1.4:1. Moreover, with the increase in aging time, the breakdown strength decreased and the compression modulus increased.

Exposure to pesticides and risk of colorectal cancer: A systematic review and meta-analysis.

Colorectal cancer (CRC) is a widespread malignancy worldwide, and its relationship with pesticide exposure remains inconclusive. This study aims to elucidate the relationship between pesticide exposure and the risk of colon, rectal, or CRC, focusing on specific pesticide groups. We conducted an extensive literature search for peer-reviewed studies published up to March 31, 2023. Summary risk ratios (RR) and their corresponding 95% confidence intervals (CI) were calculated using stratified random-effects meta-analyses, taking into account different types of exposure and outcomes, and various exposed populations and pesticide subgroups. This approach aimed to address the substantial heterogeneity observed across the literature. We also assessed heterogeneity and potential small-study effects to ensure the robustness of our findings. From the 50 studies included in this review, 33 contributed to the meta-analysis. Our results indicate a significant association between herbicide exposure and colon cancer in both lifetime-days (LDs) (RR = 1.20; 95% CI = 1.01-1.42) and intensity-weighted lifetime-days (IWLDs) (RR = 1.29, 95% CI = 1.12-1.49) exposure. Similarly, insecticide exposure was associated with an increased risk of colon cancer in IWLDs (RR = 1.32; 95% CI = 1.02-1.70) exposure, and rectal cancer in any versus never exposure (RR = 1.21; 95% CI = 1.07-1.36), IDs (RR = 1.86; 95% CI = 1.30-2.67) and IWLDs (RR = 1.70; 95% CI = 1.03-2.83) exposure. While these findings suggest significant associations of herbicide and insecticide exposure with colon and rectal cancer, respectively, further research is needed to explore the impact of other pesticide groups and deepen our understanding of pesticide exposure. These results have important implications for policymakers and regulators, underscoring the need for stricter supervision and regulation of pesticide use to mitigate CRC risk.

Calcium silicate/gelatin composite scaffolds with controllable degradation behavior: Fabrication and evaluation.

Calcium silicate can be used as an excellent material for biodegradable bone scaffolds because it can provide bioactive ions to promote bone regeneration. However, the brittleness and rapid degradation of calcium silicate scaffolds have significantly limited their clinical application. In this work, the calcium silicate scaffolds printed by DLP technology were immersed in a gelatin solution under high vacuum condition to obtain calcium silicate/gelatin composite scaffolds with good mechanical and biological properties. Then, genipin was used as a cross-linker for gelatin to control the degradation properties of the composite scaffolds. The initial compressive strength and toughness of the composite scaffolds were 5.0 times and one order of magnitude higher than those of the pure calcium silicate scaffolds, respectively. The gelatin on the surface of the scaffolds could effectively act as a protective layer to regulate the degradation behaviors of the calcium silicate substrate through controlling the crosslinking degree of the gelatin. After degrading for 14 days, the composite scaffolds at 1.0 % genipin concentration exhibited the highest compressive strength of 8.6 ± 0.8 MPa, much higher than that of the pure ceramic scaffold (1.5 ± 0.3 MPa). It can be found that the toughness of the composite scaffolds were almost over 13.2 times higher than that of the pure ceramic scaffold during degradation, despite the higher toughness loss for the former. Furthermore, the composite scaffolds showed enhanced cell biocompatibility and viability. These results demonstrate that the calcium silicate/gelatin composite scaffolds can be a promising candidate in bone tissue regeneration.

Usefulness of magnetic resonance imaging characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in spinal cord.

AIM: The aim of this study was to determine the usefulness of magnetic resonance imaging (MRI) characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in the spinal cord. MATERIALS AND METHODS: Fifty-eight patients with spinal cord gliomas were enrolled in this study. The H3 K27 gene status was identified by Sanger sequencing or immunohistochemistry test of resection tumor specimens. The MR imaging characteristics were evaluated and compared between H3 K27M-mutant and wildtype gliomas using the χ2 test and the Mann-Whitney U test. RESULTS: Of 58 recruited patients, 23 (39.7%) were diagnosed with H3 K27M-mutant glioma. The H3 K27M-mutant gliomas were found to more likely occur in men compared with wildtype gliomas (87.0% vs. 42.9%, p = 0.001). On T2-weighted MR images, the signal-to-noise ratio (SNR) of H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (103.9 ± 72.0 vs. 168.9 ± 86.8, p < 0.001). Of 35 wildtype tumors, 60% showed well-defined margin but this feature was not found in all mutant tumors (p < 0.001). The SNR of tumors on contrast-enhanced T1-weighted images of the H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (187.7 ± 160.4 vs. 295.1 ± 207.8, p = 0.006). Receiver operating-characteristic analysis revealed that area under curve (AUC) of combination of 1/SNR on T2-weighted images, 1/SNR on contrast-enhanced T1-weighted images, ill-defined margin, and sex reached 0.937 (95% CI, 0.873-1.000) in discriminating H3 K27M-mutant gliomas. CONCLUSIONS: The MR imaging characteristics are valuable in discriminating H3 K27M-mutant from wildtype gliomas in the spinal cord and the combination of these imaging features with sex had a high strength in this discrimination.

Effects of Traditional Chinese Medicine Five-Element Music Therapy Combined with Mirtazapine on Depression and Limb Function Recovery After Ischemic Stroke.

Objective: To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic stroke. Methods: A total of 110 patients treated in the Departments of Geriatrics, Cardiology, and Psychology of three hospitals in Qinhuangdao City, Hebei Province, China from October 2022 to August 2023 were selected. Based on the scores of 24-item Hamilton Depression Scale (HAMD-24), Barthel (BL) index, and National Institute of Health Stroke Scale (NIHSS) before enrollment, the patients were randomly divided into control group (n = 58) and experimental group (n = 52). The patients in control group were treated with limb rehabilitation, while those in experimental group underwent limb rehabilitation combined with five-element music therapy and mirtazapine. Results: After 12 weeks of treatment and observation, 11 patients in control group and 9 patients in experimental group withdrew from this trail. As for the proportions of score changes, experimental group had higher decline proportions of HAMD-24 score and NIHSS score as well as an increased proportion of BL index score than control group, which were 43.97%, 69.32%, and 44.12%, respectively. Conclusion: TCM five-element music therapy combined with mirtazapine significantly improves depression and limb function recovery after ischemic stroke.

[Efficacy and Prognostic Factors of Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia].

OBJECTIVE: To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors. METHODS: Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed. RESULTS: The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024). CONCLUSION: Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.

Short-term effect of meteorological factors and extreme weather events on daily outpatient visits for dry eye disease between 2013 and 2020: a time-series study in Urumqi, China.

Dry eye disease (DED) is a common disorder of tear secretion on the ocular surface caused by multiple factors with dry eyes as the main symptom, but until now studies focusing on relationship between local meteorological factors and ocular surface diseases in Urumqi are very limited. Besides, the effects of long-term and extreme meteorological factors on DED and the lag effect have not been fully evaluated. Electronic case information of 9970 DED outpatients from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China) between January 1, 2013, and December 31, 2020, was screened and analyzed. We used a time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) to fit the effects of exposure to different meteorological factors and extreme weather on DED outpatient visits. Subgroup analyses were further performed for gender, age, and season. The results showed that exposure to extremely low mean temperature (P1:RR = 1.18), atmospheric pressure (P1:RR = 1.11), and extremely high relative humidity (P99:RR = 1.35) were the risk factors, while extremely high atmospheric pressure (P90:RR = 0.883) and extremely low humidity (P10:RR = 0.856) appeared to have a positive effect on reduced risk of DED. Relative humidity exhibited a 1-day lag effect (RR = 1.06). Increased mean temperature positively affected female DED patients (RR = 0.761) with similar effects in the cold season (RR = 0.926). However, elevated relative humidity had a negative effect on female patients (RR = 1.14). We conducted the first large sample size time-series analysis study in this major city at the farthest distance from the ocean in the world and in northwest China, confirming the association of DED outpatient visits with the remaining three meteorological factors except wind speed in Urumqi, and a larger sample size multi-center epidemiological study with a longer duration is still needed.

Association of retinopathy with risk of all-cause and specific-cause mortality in the National Health and Nutrition Examination Survey, 2005 to 2008.

Objective: This study aimed to elucidate the relationship between retinopathy status or severity and the all-cause and specific-cause mortality risk based on the updated National Health and Nutrition Examination Survey (NHANES) database and 2019 Public Access Link mortality file. Methods: In this prospective cohort study, a total of 6,797 participants aged over 40 years based on NHANES 2005-2008 were analyzed. The severity of retinopathy was classified into 4 grades-no retinopathy, mild non-proliferative retinopathy (NPR), moderate to severe NPR, and proliferative retinopathy (PR). Multiple covariate-adjusted Cox proportional hazards regression models and Fine and Gray competing risk regression models were used to assess the all-cause and cause-specific mortality risks, respectively. The propensity score matching (PSM) approach was also applied additionally to adequately balance between-group covariates to validate our findings. Results: A final total of 4,808 participants representing 18,282,772 United States (US) non-hospitalized participants were included for analysis, 50.27% were male (n = 2,417), 55.32% were non-hispanic white (n = 2,660), and mean [SE] age, 56.10 [0.40] years. After a median follow-up of 12.24 years (interquartile range, 11.16-13.49 years), 1,164 participants died of all-cause mortality, of which 941 (80.84%) died without retinopathy and 223 (19.16%) died with retinopathy at baseline. The presence of retinopathy was associated with increased all-cause mortality, cardiovascular disease (CVD), and diabetes mellitus (DM)-specific mortality, and the results remain consistent after PSM. Severity analysis showed that only mild NPR was associated with an increased all-cause mortality risk (hazard ratio (HR) = 2.01; 95% confidence interval (CI), 1.00-4.03), while increased CVD and DM-specific mortality risk were associated with all grades of retinopathy and were exponentially greater with increasing retinopathy severity, and the trend test was also significant (P for trend 0.004 and 0.04, respectively). Discussion: Our findings suggest that the diagnosis of retinopathy is an independent risk factor for all-cause mortality in people over 40 years old. Retinopathy grading is significantly associated with the survival risk of patients with CVD or DM, it can be a valuable predictor in the stratified management and risk warning of CVD or DM patients, as well as in the monitoring of systemic vasculopathy status.

Monkeypox presenting as a chancre-like rash: A case report.

BACKGROUND: Since May 2022, outbreaks of monkeypox have occurred in many countries around the world, and several cases have been reported in China. CASE SUMMARY: A 38-year-old man presented with a small, painless, shallow ulcer on the coronary groove for 8 d. One day after the rash appeared, the patient developed inguinal lymphadenopathy with fever. The patient had a history of male-male sexual activity and denied a recent history of travel abroad. Monkeypox virus was detected by quantitative polymerase chain reaction from the rash site and throat swab. Based on the epidemiological history, clinical manifestations and nucleic acid test results, the patient was diagnosed with monkeypox. CONCLUSION: Monkeypox is an emerging infectious disease in China. Monkeypox presenting as a chancre-like rash is easily misdiagnosed. Diagnosis can be made based on exposure history, clinical manifestations and nucleic acid test results.

[Analysis on Cellular Immune Function Recovery after HLA Mismatched Allogeneic Hematopoietic Stem Cell Micro-Transp- lantation in Elderly AML Patients].

OBJECTIVE: To investigate the recovery of cellular immunity in elderly patients with acute myeloid leukemia (AML) after micro-transplantation (MST) and the changes of cellular immunity during relapse, as well as their clinical significance. METHODS: A total of 41 elderly AML patients who received MST treatment in a single center and 25 healthy elderly people were included. Immune function among different age groups in normal population was compared. Furthermore, immune fuction was compared between elderly AML patients of different age groups who achieved continuous complete remission (CR) after MST treatment and normal controls, between high risk group and medium-low risk group, as well as among before diagnosis, after CR, and relapse. Peripheral blood of patients and normal controls was collected, and the percentage of lymphocyte subsets was detected by multi-color flow cytometry. RESULTS: Thirty-five patients achieved CR after MST treatment while six patients did not. After MST treatment, CD3+ T cells, CD8+T cells and activated T cells in all age groups were higher than normal. Significant recovery of CD3+ and CD8+T cells was observed in both high risk and medium-low risk groups, and the overall recovery of immune cells in medium-low risk group was better. It was also observed that B lymphocytes and NK cells could not return to normal levels within 1 year after MST treatment. The proportion of CD3+ T cells, CD4+ T cells, and CD4/CD8 ratio were significantly decreased during relapse compared with continuous CR after MST (P<0.05). CONCLUSION: MST treatment can promote the recovery of CD3+T cells, CD8+T cells and other killer cells, so as to improve the cellular immune function of elderly patients, which provides a new immune cell therapy for elderly AML.

Hematopoietic stem cell microtransplantation in patients aged over 70 with acute myeloid leukemia: a multicenter study.

In the era of molecular targeted drugs, elderly patients with acute myeloid leukemia (AML) are still very difficult to treat, especially those older than 70 years. The decline in immune function leads to serious infection and disease recurrence. The microtransplant treatment regimen (MST) chemotherapy combined with allogeneic hematopoietic stem cell infusion is a new cell therapy regimen. The aim of this MST study was to improve the survival of elderly patients by graft versus leukemia action and improving T-cell immune function. From May 2012 to July 2020, one hundred and eleven patients aged 70 to 88 years with de novo AML were analyzed retrospectively. After induction chemotherapy, patients whom complete remission (CR) was achieved were given another 2 cycles of postremission therapy. The MST groups were given allogeneic stem cell infusion after each chemotherapy cycle. CR, leukemia-free survival, and overall survival (OS) were compared between groups. Additionally, the immune function and the T cell receptor (TCR) library of T cells were detected and analyzed. The MST group exhibited an encouragingly high CR rate (63.8%), even in high-risk patients (54%), and this rate was significantly higher than that in the chemotherapy alone group. The 1-year OS of MST patients was 57.7%, and it was 55.9% in the high-risk group. It was only 37.3% in the chemotherapy alone group. Higher numbers of naive T cells were found in the MST population than in the chemotherapy alone group. More updated T-cell clones were observed in MST patients by T-cell receptor repertoire analysis with a next-generation sequencing methodology. These results suggest that MST is a safe and practical regimen conducive to longer-term survival in patients of a highly advanced age with AML. Furthermore, it has broad clinical value in the recovery of immune function in elderly patients.

Perfluoroalkyl and polyfluoroalkyl substances and hypertensive disorders of pregnancy: A systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDP), including gestational hypertension (GH) and preeclampsia (PE), cause significant morbidity and mortality among pregnant women. Several environmental toxins, particularly those that affect the normal function of the placenta and the endothelium, are emerging as potential risk factors for HDP. Among them, per- and polyfluoroalkyl substances (PFAS), widely used in a variety of commercial products, have been related to a variety of adverse health effects including HDP. This study was conducted by searching three databases for observational studies reporting associations between PFAS and HDP, all of which were published before December 2022. We used random-effects meta-analysis to calculate pooled risk estimates, and assessing each combination of exposure and outcome for quality and level of evidence. In total, 15 studies were included in the systematic review and meta-analysis. The results from meta-analyses showed that risk of PE was increased with exposure to PFOA (perfluorooctanoic acid) (RR = 1.39, 95% CI = 1.05, 1.85; N = 6 studies; exposure = 1 ln-unit increment; low certainty), PFOS (perfluorooctane sulfonate) (RR = 1.51, 95% CI = 1.23, 1.86; N = 6 studies; exposure = 1 ln-unit increment; moderate certainty), and PFHxS (perfluorohexane sulfonate) (RR = 1.39, 95% CI = 1.10, 1.76; N = 6 studies; exposure = 1 ln-unit increment; low certainty). PFOS was also associated with an increased risk of HDP (RR = 1.39, 95% CI = 1.10, 1.76; exposure = 1 ln-unit increment; low certainty). Exposure to legacy PFAS (PFOA, PFOS, PFHxS) is associated with an increased risk of PE, and PFOS is further associated with HDP. In view of the limitations of meta-analysis and quality of evidence, these findings should be interpreted with caution. Further research is required that assesses exposure to multiple PFAS in diverse and well-powered cohorts.