This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To study the changes of volume and cognitive function in hypothalamic subregions based on automated MRI segmentation at various stages of adult life and the correlation between them.Methods Totally 314 healthy subjects aged 20-89 years old were selected from the public database of Dallas Lifespan Brain Study(DLBS),and then divided into a youth group(20-35 years old),an early-middle age group(36-50 years old),a late-middle age group(51-65 years old)and an elderly age group(66-89 years old).The structural magnetic resonance imaging(sMRI)images of the 314 subjects were treated with Freesurfer software to determine the volumes of the anterosuperior,anterior-inferior,middle-superior,middle-inferior and posterior subregions of the right and left sides of the hypothalamus.Differences in hypothalamic subregion volumes between the 4 groups were compared using analysis of covariance,and multiple comparisons between the 4 groups were performed using Bonferroni correction.Pearson's correlation coefficients were used to analyze the correlations of the hypothalamic subregion volumes with the scores of mini mental state examination(MMSE),digit comparison(DC)test,digit symbol(DS)test,and Hopkins verbal learning test(HVLT).Results The volumes of all the hypothalamic subregions except the right anterior inferior part decreased significantly with age(P＜0.05).All the hypothalamic subregions except the right anterior inferior part had the volumes correlated with MMSE scores positively(P＜0.05);the DC test scores were correlated positively with all the hypothalamic subregion volumes(P＜0.05);the DS test scores were correlated positively with the volumes of the hypothalamic subregions except the bilateral anterior-inferior part(P＜0.05);the scores of HVLT immediate memory test were positively correlated with the anterior-superior,middle-superior and posterior subregion volumes of the right and left sides of the hypothalamus(P＜0.05);the scores of HVLT delayed memory test were correlated positively with the volumes of the bilat-eral anterior-superior and left-middle-superior subregions(P＜0.05);the scores of HVLT delayed recognition test did not cor-relate with all the hypothalamic subregions(P＞0.05);the volumes of the bilateral hypothalamus were positively correlated with the scores of MMSE,DC test,DS test and HVLT immediate memory test(P＜0.05).Conclusion Volume changes in some hy-pothalamic subregions are associated with age-related memory decline during adult aging,which can be used to assess the risk of memory loss throughout adulthood.[Chinese Medical Equipment Journal,2024,45(5):8-15]

Hashimoto's thyroiditis(HT)is a common endocrine disease,which can be classified into the category of goiter disease in traditional Chinese medicine.Professor LIU Min believes that the pathogenesis of HT is closely related to the heart and gallbladder,and its pathogenesis is due to the gallbladder constraint failing to descend and the disturbance of pivot,together with insufficient heart-qi and the disharmony between the nutritive qi and the defensive qi.For the treatment of HT,the modified Chaihu Guizhi Decoction is often used,which is mainly composed of Bupleuri Radix,Cinnamomi Ramulus,Scutellariae Radix,Pinelliae Rhizoma Praeparatum,Ginseng Radix et Rhizoma Rubra,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Jujubae Fructus,Paeoniae Radix Alba,Os Draconis,Ostreae Concha,and Zingiberis Rhizoma Recens.Chaihu Guizhi Decoction has the actions of soothing gallbladder and relieving depression,restoring the function of shaoyang pivot,regulating nutritive qi and the defensive qi,and benefiting heart spirit,which exactly accords with the HT's pathogenesis of gallbladder constraint failing to descend and insufficient heart-qi.In the clinical treatment of HT,the modification of the drugs should be performed according to the concurrent syndromes of the patients,and the dosage of the drugs should also be adjusted.In addition to drug treatment,the attention should also be addressed to the adjustment of patients'lifestyle and dietary habits and to the emotional counseling,thus to achieve significant effect.

Objective:To investigate the clinical and genetic features of the patient with neurodevelopmental disorders characterized by thickened corpus callosum caused by MAST1 gene mutation. Methods:Clinical data and auxiliary examination of a child with neurodevelopmental disorders caused by MAST1 gene mutation who was admitted to Henan Children′s Hospital in September 2022 were collected, and whole exome sequencing technology was applied to analyze the genetics of the child. Results:The patient was a 2 years and 8 months old male, with a clinical phenotype including intellectual, motor, and speech development disorders. Brain magnetic resonance imaging (MRI) showed thickened corpus callosum, nodular heterotopia of the left ventricle body.Whole exome sequencing showed the MAST1 gene with c.578T>G(p.Met193Arg) heterozygous missense variant, which was a unreported de novo pathogenic variant and both of his parents were wild-type. Conclusions:Diseases caused by MAST1 gene mutations are relatively rare, the main clinical features are neurodevelopmental disorders and brain structural abnormalities, and MRI shows an enlarged corpus callosum.The heterozygous missense variant c.578T>G(p.Met193Arg) of the MAST1 gene is the genetic cause of this case.

Background and Objectives: Long-term pathological myocardial hypertrophy (MH) seriously affects the normal function of the heart. Dronedarone was reported to attenuate left ventricular hypertrophy of mice. However, the molecular regulatory mechanism of dronedarone in MH is unclear. Methods: Angiotensin II (Ang II) was used to induce cell hypertrophy of H9C2 cells.Transverse aortic constriction (TAC) surgery was performed to establish a rat model of MH.Cell size was evaluated using crystal violet staining and rhodamine phalloidin staining.Reverse transcription quantitative polymerase chain reaction and western blot were performed to detect the mRNA and protein expressions of genes. JASPAR and luciferase activity were conducted to predict and validate interaction between forkhead box O3 (FOXO3) and protein kinase inhibitor alpha (PKIA) promoter. Results: Ang II treatment induced cell hypertrophy and inhibited sirtuin 1 (SIRT1) expression, which were reversed by dronedarone. SIRT1 overexpression or PKIA overexpression enhanced dronedarone-mediated suppression of cell hypertrophy in Ang II-induced H9C2 cells. Mechanistically, SIRT1 elevated FOXO3 expression through SIRT1-mediated deacetylation of FOXO3 and FOXO3 upregulated PKIA expression through interacting with PKIA promoter. Moreover, SIRT1 silencing compromised dronedaronemediated suppression of cell hypertrophy, while PKIA upregulation abolished the influences of SIRT1 silencing. More importantly, dronedarone improved TAC surgery-induced MH and impairment of cardiac function of rats via affecting SIRT1/FOXO3/PKIA axis. Conclusions Dronedarone alleviated MH through mediating SIRT1/FOXO3/PKIA axis, which provide more evidences for dronedarone against MH.

OBJECTIVE: To explore clinical efficacy of unilateral and bilateral nail-rod system fixation in single-level intervertebral fusion fixation of lumbar disc herniation (LDH) and instability with unilateral dual-channel spinal endoscopy. METHODS: The clinical data of 63 patients with LDH complicated with instability treated by unilateral double-channel spinal endoscopy from March 2021 to June 2022 were retrospectively analyzed. According to intraoperative fixation methods, the patients were divided into two groups, included unilateral nail rod system fixation group(unilateral group) and bilateral nail rod system fixation group(bilateral group). There were 31 patients in unilateral group, including 15 males and 16 females; aged from 40 to 67 years old with an average of (54.65±7.32) years old; 3 patients with L_3,4, 15 patients with L_4,5, 13 patients with L₅S₁. There were 32 patients in bilateral group, including 18 males and 14 females, aged from 43 to 68 years old with an average of (56.19±6.63) years old;4 patients with L_3,4, 17 patients with L_4,5, 11 patients with L₅S₁. The time of operation, length of incision, operation time, length of hospital stay, cost of treatment, occurrence of complications and adverse events were recorded and compared between two groups. Visual analogue scale (VAS) of lumbar and leg pain, Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI) were compared before operation, 3 and 12 months after operation. MacNab standard was used to evaluate clinical effect. RESULTS: Both of two groups were successfully completed operation and followed up. In unilateral fixation group, follow-up time, operation time, incision length, postoperative ambulation time, hospital stay and treatment cost were (11.81±1.08) months, (122.48±13.86) min, (3.15±0.45) cm, (3.06±0.73) d, (6.87±1.09) d, and (3.49±0.09) ten thousand yuan;while (11.47±1.16) months, (134.94±10.94) min, (6.45±0.83) cm, (3.19±0.86) d, (7.03±1.03) d, (3.77±0.12) ten thousand yuan in bilateral fixation group, respectively;there were significant differences in operation time, incision length and treatment cost between two groups (P<0.05), no significant difference in follow-up time, postoperative ambulation time and hospital stay (P>0.05). There were no significant difference in VAS of low back pain, JOA score, ODI and MacNab grade between two groups before and after operation (P>0.05). No significant complications and adverse events were observed between two groups after operation. CONCLUSION Both of unilateral and bilateral nail rod system for the treatment of LDH with instability could achieve the expected results. Unilateral fixation has more advantageous than bilateral fixation in terms of operation time, incision length and treatment cost. For patients with osteoporosis before operation or insufficient fixation strength of unilateral pedicle nails during surgery, bilateral fixation is feasible to enhance reliability of fixation.
Humans ; Male ; Female ; Middle Aged ; Spinal Fusion/methods* ; Endoscopy/methods* ; Aged ; Adult ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Retrospective Studies

Objective:To analyze the clinical characteristics and genetic variation of 2 children with developmental and epileptic encephalopathy 8 (DEE8).Methods:Whole-exome sequencing (WES) was performed to determine the potential variants in the probands. Candidate variants identified by WES were validated by Sanger sequencing and quantitative real-time polymerase chain reaction. X chromosome inactivation (XCI) detection was performed in the proband 1′s mother and proband 2 to detect the allelic expression difference of ARHGEF9. Results:Both of the cases showed global developmental delay. Proband 1 presented with delayed motor and speech development, intellectual disability, and seizures. Electroencephalography of proband 1 showed slow background activity, with spikes, spike and waves in bilateral frontal and midline regions during sleep. While proband 2 showed delay in acquisition of language, motor skills, and cognition, but no seizures. It was identified that proband 1 carried a novel maternally derived heterozygous splicing variant (c.925-2A>T) in ARHGEF9 by WES, which was verified in Sanger sequencing. The XCI in proband 1′s mother was observed, and the expression ratio of mutant ARHGEF9 and wild-type was 0∶100%. A novel exon 3-10 heterozygous deletion of ARHGEF9 was identified in proband 2, and this variant was not found in his unaffected parents. Conclusions:DEE8 disorders are relatively rare. Most of the patients have varying degrees of neurodevelopmental phenotype, but epilepsy is not a specific clinical manifestation. ARHGEF9 gene deletion and splicing variation may be the genetic cause of the 2 probands, and above findings have enriched the spectrum of variation and phenotype of DEE8.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.