Objective:To investigate the protective effects and mechanisms of targeted inhibition of type 3 deiodinase (Dio3) on skeletal muscle mitochondria in sepsis.Methods:① In vivo experiments: adeno-associated virus (AAV) was employed to specifically target Dio3 expression in the anterior tibial muscle of rats, and a septic rat model was generated using cecal ligation and puncture (CLP). The male Sprague-Dawley (SD) rats were divided into shNC+Sham group, shD3+Sham group, shNC+CLP group, and shD3+CLP group by random number table method, with 8 rats in each group. After CLP modeling, tibial samples were collected and Western blotting analysis was conducted to assess the protein levels of Dio3, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), and silence-regulatory protein 1 (SIRT1). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was utilized to examine mRNA expression of genes including thyroid hormone receptors (THRα, THRβ), monocarboxylate transporter 10 (MCT10), mitochondrial DNA (mtDNA), and PGC1α. Transmission electron microscopy was employed to investigate mitochondrial morphology. ② In vitro experiments: involved culturing C2C12 myoblasts, interfering with Dio3 expression using lentivirus, and constructing an endotoxin cell model by treating cells with lipopolysaccharide (LPS). C2C12 cells were divided into shNC group, shD3 group, shNC+LPS group, and shD3+LPS group. Immunofluorescence colocalization analysis was performed to determine the intracellular distribution of PGC1α. Co-immunoprecipitation assay coupled with Western blotting was carried out to evaluate the acetylation level of PGC1α. Results:① In vivo experiments: compared with the shNC+Sham group, the expression of Dio3 protein in skeletal muscle of the shNC+CLP group was significantly increased (Dio3/β-Tubulin: 3.32±0.70 vs. 1.00±0.49, P < 0.05), however, there was no significant difference in the shD3+Sham group. Dio3 expression in the shD3+CLP group was markedly reduced relative to the shNC+CLP group (Dio3/β-Tubulin: 1.42±0.54 vs. 3.32±0.70, P < 0.05). Compared with the shNC+CLP group, the expression of T3-regulated genes in the shD3+CLP group were restored [THRα mRNA (2 -ΔΔCt): 0.67±0.05 vs. 0.33±0.01, THRβ mRNA (2 -ΔΔCt): 0.94±0.05 vs. 0.67±0.02, MCT10 mRNA (2 -ΔΔCt): 0.65±0.03 vs. 0.57±0.02, all P < 0.05]. Morphology analysis by electron microscopy suggested prominent mitochondrial damage in the skeletal muscle of the shNC+CLP group, while the shD3+CLP group exhibited a marked improvement. Compared with the shNC+Sham group, the shNC+CLP group significantly reduced the number of mitochondria (cells/HP: 10.375±1.375 vs. 13.750±2.063, P < 0.05), while the shD3+CLP group significantly increased the number of mitochondria compared to the shNC+CLP group (cells/HP: 11.250±2.063 vs. 10.375±1.375, P < 0.05). The expression of mtDNA in shNC+CLP group was markedly reduced compared with shNC+Sham group (copies: 0.842±0.035 vs. 1.002±0.064, P < 0.05). Although no difference was detected in the mtDNA expression between shD3+CLP group and shNC+CLP group, but significant increase was found when compared with the shD3+Sham group (copies: 0.758±0.035 vs. 0.474±0.050, P < 0.05). In the shD3+CLP group, PGC1α expression was significantly improved at both transcriptional and protein levels relative to the shNC+CLP group [PGC1α mRNA (2 -ΔΔCt): 1.49±0.13 vs. 0.68±0.06, PGC1α/β-Tubulin: 0.76±0.02 vs. 0.62±0.04, both P < 0.05]. ② In vitro experiments: post-24-hour LPS treatment of C2C12 cells, the cellular localization of PGC1α became diffuse; interference with Dio3 expression promoted PGC1α translocation to the perinuclear region and nucleus. Moreover, the acetylated PGC1α level in the shD3+LPS group was significantly lower than that in the shNC+LPS group (acetylated PGC1α/β-Tubulin: 0.59±0.01 vs. 1.24±0.01, P < 0.05), while the expression of the deacetylating agent SIRT1 was substantially elevated following Dio3 inhibition (SIRT1/β-Tubulin: 1.04±0.04 vs. 0.58±0.03, P < 0.05). When SIRT1 activity was inhibited by using EX527, PGC1α protein expression was notably decreased compared to the shD3+LPS group (PGC1α/β-Tubulin: 0.92±0.03 vs. 1.58±0.03, P < 0.05). Conclusion:Inhibition of Dio3 in skeletal muscle reduced the acetylation of PGC1α through activating SIRT1, facilitating nuclear translocation of PGC1α, thereby offering protection against sepsis-induced skeletal muscle mitochondrial damage.

Objective To observe the effects of electroacupuncture on the learning and memory abilities of Alzheimer disease(AD)rats;To explore its potential mechanism based on proteomics.Methods Totally 36 SD male rats were randomly divided into sham-operation group,model group and heart meridian acupoints group,with 12 rats in each group.Aβ1-42 were injected into the bilateral hippocampus to establish AD rat model,the sham-operation group was injected with an equal volume of normal saline.The heart meridian acupoints group received electroacupuncture treatment,accompanied by a stimulation time of 20 minutes,rest for 1 day after 6 days of electroacupuncture for 7 consecutive weeks.The Morris water maze experiment was used to evaluate the learning and memory abilities of AD rats,tandem mass tag(TMT)labeling technology and bioinformatics analysis were used to screen core differentially expressed proteins in important typical pathways,and key differentially expressed protein was verified by parallel reaction monitoring(PRM).Results There was no statistically significant difference in swimming speed between each group of rats(P>0.05).Compared with the sham-operation group,the escape latency of Morris water maze experiment in the model group increased significantly(P<0.01);compared with the model group,the escape latency of heart meridian acupoints group was significantly shortened on the 2-4th day(P<0.01).A total of 209 differentially expressed proteins were identified in different groups using TMT labeling quantification,among which 12 proteins showed significant changes among the 3 groups.GO annotation involved biological processes such as metal ion transport,sodium ion transport,and sodium ion transmembrane transport,as well as cellular components such as synapses,presynapse,and synaptic vesicle,involving solute:sodium symporter activity,organic acid:sodium symporter activity,amino acid:cation symporter activity,amino acid:sodium symporter activity,and other molecular functions;KEGG analysis significantly enriched the synaptic vesicle pathway.The PRM validation results indicated that electroacupuncture at the heart meridian acupoints could reduce the expressions of sodium and chloride dependent GABA transporter protein 3(GAT3),which was consistent with the quantitative detection results of TMT labeling quantification.Conclusion Electroacupuncture at the heart meridian acupoints can improve the learning and memory abilities of AD rats,possibly by regulating the expression of synaptic transporter GAT3 on the synaptic vesicle pathway to exert neuroprotective effects.

Objective: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with lightchain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. Materials and Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49–63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At followup after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Results: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%–1.1%] vs. 1.7% [-5.5%–7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%–1.3%] vs. 2.0% [-3.0%–5.0%]; P = 0.01) compared with those with inferior response. Conclusion Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.
Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China/epidemiology* ; Diseases in Twins/genetics* ; Hyperlipidemias/genetics* ; Metabolic Diseases ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

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

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Objective: To analyze the clinical characteristics of the neonates infected with SARS-CoV-2 during the Omicron outbreak in Shanghai 2022. Methods: In this retrospective case series study, all the 16 neonates with SARS-CoV-2 Omicron infection who were admitted to the neonatal unit in Shanghai Public Health Clinical Center from March 1^st to May 31^st, 2022 were enrolled. Their epidemiological history, clinical manifestations, nucleic acid cycle threshold (Ct) value and outcomes were analyzed. Based on maternal vaccination, they were divided into vaccinated group and unvaccinated group. Rank sum test and Chi-square test were used for the comparison between the groups. Results: Among the 16 neonates, 10 were male, and 6 were female. All the infants were full-term. The infection was confirmed at the age of 12.5 (8.0, 20.5) days. All the neonates had a history of exposure to infected family members, and thus horizontal transmission was the primary mode. Four infants were asymptomatic, 12 were symptomatic, and there were no severe or critical cases. The most common clinical manifestation was fever (11 cases), with the highest temperature of 38.1 (37.9, 38.3) ℃ and a course of 1-5 days. Other clinical manifestations included nasal obstruction (3 cases), runny nose (2 cases), cough (2 cases), poor feeding (2 cases), vomiting (1 case), and mild tachypnea (1 case). The complete blood counts of all neonates were within the normal range, and the C-reactive protein increased slightly in 1 infant. Chest imaging was performed in 2 infants, showing mild focal exudative changes. Nucleic acid turned negative (Ct value ≥35) within 7-15 days after diagnosis. All neonates fully recovered after supportive treatment, and the length of hospitalization was 13 (10, 14) days. In the telephone follow-up 2 weeks after discharge for all 16 cases, no infant showed reoccurrence of clinical manifestations or nucleic acid reactivation. Maternal vaccination was not significantly correlated with symptomatic infection or the persistence of positive nucleic acid result in neonates (all P>0.05). Conclusions: Horizontal transmission is the primary mode for neonatal SARS-CoV-2 Omicron infection. Neonatal infections are usually mild or asymptomatic, with good short-term outcomes. And their clinical manifestations and laboratory examinations are nonspecific.
Infant, Newborn ; Male ; Female ; Humans ; SARS-CoV-2 ; COVID-19 ; Retrospective Studies ; China/epidemiology* ; Fever ; Disease Outbreaks ; Nucleic Acids

Objective: To summarize the management and short-term outcomes of neonates delivered by mothers infected with SARS-CoV-2 Omicron variant. Methods: A retrospective study was performed on 158 neonates born to mothers infected with SARS-CoV-2 Omicron variant admitted to the isolation ward of Children's Hospital of Fudan University from March 15^th, 2022 to May 30^th, 2022. The postnatal infection control measures for these neonates, and their clinical characteristics and short-term outcomes were analyzed. They were divided into maternal symptomatic group and maternal asymptomatic group according to whether their mothers had SARS-CoV-2 symptoms. The clinical outcomes were compared between the 2 groups using Rank sum test and Chi-square test. Results: All neonates were under strict infection control measures at birth and after birth. Of the 158 neonates, 75 (47.5%) were male. The gestational age was (38⁺³±1⁺³) weeks and the birth weight was (3 201±463)g. Of the neonates included, ten were preterm (6.3%) and the minimum gestational age was 30⁺¹ weeks. Six neonates (3.8%) had respiratory difficulty and 4 of them were premature and required mechanical ventilation. All 158 neonates were tested negative for SARS-COV-2 nucleic acid by daily nasal swabs for the first 7 days. A total of 156 mothers (2 cases of twin pregnancy) infected with SARS-CoV-2 Omicron variant, the time from confirmed SARS-CoV-2 infection to delivery was 7 (3, 12) days. Among them, 88 cases (56.4%) showed clinical symptoms, but none needed intensive care treatment. The peripheral white blood cell count of the neonates in maternal symptomatic group was significantly higher than that in maternal symptomatic group (23.0 (18.7, 28.0) × 10⁹ vs. 19.6 (15.4, 36.6) × 10⁹/L, Z=2.44, P<0.05). Conclusions: Neonates of mothers infected with SARS-CoV-2 Omicron variant during third trimester have benign short-term outcomes, without intrauterine infection through vertical transmission. Strict infection control measures at birth and after birth can effectively protect these neonates from SARS-CoV-2 infection.
Female ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; COVID-19 ; Mothers ; Pregnancy Complications, Infectious/prevention & control* ; Retrospective Studies ; SARS-CoV-2

Objective: To describe the distribution characteristics of type 2 diabetes in twins in Chinese National Twin Registry (CNTR), provide clues and evidence for revealing the influence of genetic and environmental factors for type 2 diabetes. Methods: Of all twins registered in the CNTR during 2010-2018, a total 18 855 twin pairs aged ≥30 years with complete registration information were included in the analysis. The random effect model was used to describe the population and area distribution characteristics and concordance of type 2 diabetes in twin pairs. Results: The mean age of the subjects was (42.8±10.2) years, the study subjects included 10 339 monozygotic (MZ) twin pairs and 8 516 dizygotic (DZ) twin pairs. The self-reported prevalence rate of type 2 diabetes was 2.2% in total population and there was no sighificant difference between MZ and DZ. Intra-twin pairs analysis showed that the concordance rate of type 2 diabetes was 38.2% in MZ twin pairs, and 16.0% in DZ twin pairs, the difference was statistically significant (P<0.001). The concordance rate of type 2 diabetes in MZ twin parts was higher than that in DZ twin pairs in both men and women, in different age groups and in different areas (P<0.05). Further stratified analysis showed that in northern China, only MZ twin pairs less than 60 years old were found to have a higher concordance rate of type 2 diabetes compared with DZ twin pairs (P<0.05). In southern China, the co-prevalence rate in male MZ twin pairs aged ≥60 years was still higher than that in DZ twin pairs (P<0.05). Conclusion: The twin pairs in this study had a lower self-reported prevalence of type 2 diabetes than the general population. The study results suggested that genetic factors play a role in type 2 diabetes prevalence in both men and women, in different age groups and in different areas, however, the effect might vary.
Adult ; China/epidemiology* ; Diabetes Mellitus, Type 2/genetics* ; Diseases in Twins/genetics* ; Female ; Humans ; Male ; Middle Aged ; Registries ; Twins, Dizygotic ; Twins, Monozygotic/genetics*