In recent years, the prevalence of diabetes has continued to rise, with diabetes mellitus type 2 (T2DM) being the most common form. T2DM is characterized by chronic low-grade inflammation and disruptions in insulin metabolism. Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that, upon activation, upregulates pro-inflammatory cytokines via the nuclear factor κB (NF‑κB) pathway, thereby contributing to the pathogenesis of T2DM. Peripheral 5-hydroxytryptamine (5-HT), primarily synthesized by enterochromaffin (EC) cells in the gut, interacts with 5-hydroxytryptamine receptors (5-HTRs) in key insulin-target tissues, including the liver, adipose tissue, and skeletal muscle. This interaction influences hepatic gluconeogenesis, fat mobilization, and the browning of white adipose tissue. Elevated peripheral 5-HT levels may disrupt glucose and lipid metabolism, thereby contributing to the onset and progression of T2DM. Within mitochondria, 5-HT undergoes degradation and inactivation through the enzymatic action of monoamine oxidase A (MAO-A), leading to the generation of reactive oxygen species (ROS). Excessive ROS production and accumulation can induce oxidative stress, which may further contribute to the pathogenesis of T2DM. Platelets serve as the primary reservoir for5-HT in the bloodstream. The activation of the TLR4 signaling pathway on the platelet surface, coupled with reduced expression of the 5-HT transporter on the cell membrane, leads to elevated serum 5-HT levels, potentially accelerating the progression of T2DM. Therefore, inhibition of TLR4 and reduction of peripheral 5-HT levels could represent promising therapeutic strategies for T2DM. This review explores the synthesis, transport, and metabolism of peripheral 5-HT, as well as its role in TLR4-mediated T2DM, with the aim of providing novel insights into the clinical diagnosis, treatment, and evaluation of T2DM.

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.
Humans ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Transplantation ; Heterocyclic Compounds/adverse effects* ; Lymphoma/drug therapy* ; Lymphoma, T-Cell/therapy* ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Transplantation, Autologous

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset, posing a serious threat to human physical and mental health. The cognitive impairments caused by AD are generally diffuse and overlap symptomatically with other neurodegenerative diseases. Moreover, the symptoms of AD are often covert, leading to missed opportunities for optimal treatment after diagnosis. Therefore, early diagnosis of AD is crucial. In vitro diagnostic biomarkers not only contribute to the early clinical diagnosis of AD but also aid in further understanding the disease's pathogenesis, predicting disease progression, and observing the effects of novel candidate therapeutic drugs in clinical trials. Currently, although there are numerous biomarkers associated with AD diagnosis, the complex nature of AD pathogenesis, limitations of individual biomarkers, and constraints of clinical detection methods have hindered the development of efficient, cost-effective, and convenient diagnostic methods and standards. This article provides an overview of the research progress on in vitro diagnostic biomarkers and detection methods related to AD in recent years.
Humans ; Alzheimer Disease/diagnosis* ; Neurodegenerative Diseases ; Early Diagnosis ; Cognitive Dysfunction ; Biomarkers

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*

Objective: To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS), and to analyze the factors related to the outcomes. Methods: The clinical data of 60 children with WAS received HSCT in Shanghai Children's Medical Center from January 2006 to December 2020 were retrospectively analyzed. All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide, and a graft-versus-host disease (GVHD) prevention regimen based on cyclosporine and methotrexate. Implantation, GVHD, transplant-related complications, immune reconstitution and survival rate were observed. Survival analysis was performed by Kaplan-Meier method, and Log-Rank method was used for univariate comparison. Results: The 60 male patients had main clinical features as infection and bleeding. The age at diagnosis was 0.4 (0.3, 0.8) years, and the age at transplantation was 1.1 (0.6, 2.1) years. There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation; 35 patients received peripheral blood HSCT, and 25 cord blood HSCT. All cases were fully implanted. The incidence of acute GVHD (aGVHD) was 48% (29/60) and only 2 (7%) developed aGVHD of grade Ⅲ; the incidence of chronic GVHD (cGVHD) was 23% (13/56), and all cases were limited. The incidence of CMV and EBV infection was 35% (21/60) and 33% (20/60) respectively; and 7 patients developed CMV retinitis. The incidence of sinus obstruction syndrome was 8% (5/60), of whom 2 patients died. There were 7 cases (12%) of autoimmune hemocytopenia after transplantation. Natural killer cells were the earliest to recover after transplantation, and B cells and CD4⁺T cells returned to normal at about 180 days post HSCT. The 5-year overall survival rate (OS) of this group was 93% (95%CI 86%-99%), and the event free survial rate (EFS) was 87% (95%CI 78%-95%). EFS of non-CMV reactivation group is higher than that of CMV reactivation group (95% (37/39) vs.71% (15/21), χ²=5.22, P=0.022). Conclusions: The therapeutic efficacy of HSCT for WAS is satisfying, and the early application of HSCT in typical cases can achieve better outcome. CMV infection is the main factor affecting disease-free survival rate, which can be improved by strengthening the management of complications.
Humans ; Male ; Child ; Retrospective Studies ; Wiskott-Aldrich Syndrome/therapy* ; China ; Hematopoietic Stem Cell Transplantation/methods* ; Graft vs Host Disease/prevention & control* ; Transplantation Conditioning

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.
Child ; Female ; Male ; Humans ; Retrospective Studies ; Cytokine Release Syndrome ; COVID-19/complications* ; SARS-CoV-2 ; Brain Diseases/etiology* ; Prognosis ; Seizures ; Cytokines

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis