KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis.

Aberrant lysine lactylation (Kla) is associated with various diseases which are caused by excessive glycolysis metabolism. However, the regulatory molecules and downstream protein targets of Kla remain largely unclear. Here, we observed a global Kla abundance profile in colorectal cancer (CRC) that negatively correlates with prognosis. Among lactylated proteins detected in CRC, lactylation of eEF1A2K408 resulted in boosted translation elongation and enhanced protein synthesis which contributed to tumorigenesis. By screening eEF1A2 interacting proteins, we identified that KAT8, a lysine acetyltransferase that acted as a pan-Kla writer, was responsible for installing Kla on many protein substrates involving in diverse biological processes. Deletion of KAT8 inhibited CRC tumor growth, especially in a high-lactic tumor microenvironment. Therefore, the KAT8-eEF1A2 Kla axis is utilized to meet increased translational requirements for oncogenic adaptation. As a lactyltransferase, KAT8 may represent a potential therapeutic target for CRC.

Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling.

Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion, but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA, increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs. mtDNA was recognized by cyclic-GMP-AMP synthase (cGAS) in the DC cytosol, contributing to type I interferon (IFN) production and antitumor adaptive immunity. Thus, our findings have demonstrated how tumor cells inhibit innate sensing in DCs and suggested that the CD47-SIRPα axis is critical for DC-driven antitumor immunity.

Transcriptomic divergence of the Rheum palmatum complex derived from top-geoherb and non-geoherb areas provides the insights into geoherbalism properties of rhubarb.

Geoherb usually represents high-quality medicinal herbs with better clinical therapeutic effects, and elucidating the geoherbalism is essential for the quality improvement of traditional Chinese Medicine. However, few researches were conducted to clarify the geoherbalism based on a large scale of transcriptomics. In the present study, we compared the transcriptomes of Rheum palmatum complex derived from top-geoherb and non-geoherb areas to show the geoherbalism properties of rhubarb. A total of 412.32 Gb clean reads were obtained with unigene numbers of 100,615 after assembly. Based on the obtained transcriptome datasets, key enzyme-encoding genes involved in the anthraquinones biosynthesis were also obtained. We also found that 21 anthraquinone-related unigenes were differentially expressed between two different groups, and some of these DEGs were correlated to the content accumulation of five free anthraquinones, indicating that the gene expression profiles may promote the geoherbalism formation of rhubarb. In addition, the selective pressure analyses indicated that most paired orthologous genes between these two groups were subject to negative selection, and only a low proportion of orthologs under positive selection were detected. Functional annotation analyses indicated that these positive-selected genes related to the functions such as gene expression, substance transport, stress response and metabolism, indicating that discrepant environment also enhanced the formation of geoherbalism. Our study not only provided insights for the genetic mechanism of geoherbalism of rhubarb, but also laid more genetic cues for the future rhubarb germplasms improvement and utilization.

A chromosome-level genome reveals genome evolution and molecular basis of anthraquinone biosynthesis in Rheum palmatum.

BACKGROUND: Rhubarb is one of common traditional Chinese medicine with a diverse array of therapeutic efficacies. Despite its widespread use, molecular research into rhubarb remains limited, constraining our comprehension of the geoherbalism. RESULTS: We assembled the genome of Rheum palmatum L., one of the source plants of rhubarb, to elucidate its genome evolution and unpack the biosynthetic pathways of its bioactive compounds using a combination of PacBio HiFi, Oxford Nanopore, Illumina, and Hi-C scaffolding approaches. Around 2.8 Gb genome was obtained after assembly with more than 99.9% sequences anchored to 11 pseudochromosomes (scaffold N50 = 259.19 Mb). Transposable elements (TE) with a continuous expansion of long terminal repeat retrotransposons (LTRs) is predominant in genome size, contributing to the genome expansion of R. palmatum. Totally 30,480 genes were predicted to be protein-coding genes with 473 significantly expanded gene families enriched in diverse pathways associated with high-altitude adaptation for this species. Two successive rounds of whole genome duplication event (WGD) shared by Fagopyrum tataricum and R. palmatum were confirmed. We also identified 54 genes involved in anthraquinone biosynthesis and other 97 genes entangled in flavonoid biosynthesis. Notably, RpALS emerged as a compelling candidate gene for the octaketide biosynthesis after the key residual screening. CONCLUSION: Overall, our findings offer not only an enhanced understanding of this remarkable medicinal plant but also pave the way for future innovations in its genetic breeding, molecular design, and functional genomic studies.

Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge.

PURPOSE: To examine whether a 7-day or 24-h recall period of Perioperative Symptom Assessment for Patients Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge. METHODS: A total of 377 patients were recruited in a cohort study of patients who underwent lung surgery. We measured patient symptoms daily and weekly using the two recall period versions of the PSA-Lung scale, respectively. The psychometric properties of both versions were calculated. Spearman rank correlation coefficients and kappa (k) coefficients were used to measure the association between items score measured by the two version scales each week. Cohen's d effect size and mixed linear model were used to measure responsiveness to change over time. RESULTS: Spearman rank correlation coefficients between the symptom scores generated by the 7-day and 24-h versions (range 0.48-0.77; all P < 0.05). The correlations increased in patients in stable condition (weekly symptom change < 2). Cronbach's α coefficients for both ratings were > 0.87 and both had good test-retest reliability. The longitudinal analysis and Cohen's d effect sizes showed that both ratings had good ability to detect changes in all items. CONCLUSION: The 7-day retrospective scale was as effective as the 24-h retrospective scale in terms of psychometric performance. In the stage where the patient's symptoms change rapidly, it is recommended to use the 24-h retrospective scale for symptom monitoring. On the contrary, in a stable state, it can be considered to use the 7-day retrospective scale for monitoring to reduce the patient's burden.

Longitudinal patterns of patient-reported sleep disturbances after surgery for lung cancer.

PURPOSE: The purpose of this study was to identify longitudinal heterogeneous trajectories of sleep status, adjusted for the effect of pain over time, among patients who had surgery for lung cancer and to quantify how disturbed sleep in the hospital affects functional recovery after discharge. METHODS: We included patients from a surgical cohort (CN-PRO-Lung 1). All patients reported symptoms using the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) daily during postoperative hospitalization. Group-based dual trajectory modeling was used to investigate trajectories of disturbed sleep and pain during the first 7 days of postoperative hospitalization. Cox regression was used to compare the recovery of walking ability between the different sleep trajectories. RESULTS: Among 421 patients, disturbed sleep trajectories comprised low (31%), moderate (52%), and high (17%) groups. The surgical approach and number of chest tubes were associated with pain, and the number of chest tubes was also associated with sleep disturbances (OR = 1.99; 95% CI: 1.08-3.67). Recovery of walking ability after discharge was significantly slower in the high (median days = 16; 95% CI: 5-NA) and moderate disturbed sleep trajectory groups (median days = 5; 95%CI: 4-6) than in the low group (median days = 3; 95% CI: 3-4). CONCLUSION: Changes in disturbed sleep among patients with lung cancer followed three distinct trajectories over the first 7 days of hospitalization after surgery. Dual trajectory analyses highlighted the high concordance between specific trajectories of disturbed sleep and pain. Patients at high sleep disturbance and high levels of pain may benefit from appropriate interventions for both symptoms in combination with the patient's surgical approach and the number of chest tubes.

The panda-derived Lactiplantibacillus plantarum BSG201683 improves LPS-induced intestinal inflammation and epithelial barrier disruption in vitro.

Captive pandas are suffering from intestinal infection due to intestinal microbiota characterized by a high abundance of Enterobacteriaceae induced by long-term captivity. Probiotic supplements showed improvement in intestinal barrier function and inflammation. However, the effects of panda-derived probiotics on the intestinal epithelium and inflammation have not been elucidated. In the present study, lipopolysaccharide (LPS) impaired Caco-2 and RAW264.7 inflammatory models were applied to assess the protection of Lactiplantibacillus plantarum BSG201683 (L. plantarum G83) on barrier disruption and inflammation. The results showed that treatment with L. plantarum G83 significantly decreased the paracellular permeability to fluorescein isothiocyanate conjugated dextran (MW 4000, FITC-D4) after LPS induction. Meanwhile, L. plantarum G83 alleviated the reduction in tight junction (TJ) proteins and downregulated proinflammatory cytokines caused by LPS in Caco-2 cells. L. plantarum G83 also significantly decreased the expression and secretion of pro-inflammatory cytokines in LPS-induced RAW264.7 cells. In addition, the IL-10 increased in both Caco-2 and RAW264.7 cells after L. plantarum G83 treatment. The phagocytosis activity of RAW264.7 cells was significantly increased after L. plantarum G83 treatment. Toll-like receptor 4/ nuclear factor kappa-B (TLR4/NF-κB) signaling pathways were significantly down-regulated after L. plantarum G83 intervention, and the phosphorylation of NF-κB/p65 was consistent with this result. Our findings suggest that L. plantarum G83 improves intestinal inflammation and epithelial barrier disruption in vitro.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Stokes shift spectroscopy and machine learning for label-free human prostate cancer detection.

The Stokes shift spectra (S3) of human cancerous and normal prostate tissues were collected label free at a selected wavelength interval of 40 nm to investigate the efficacy of the approach based on three key molecules-tryptophan, collagen, and reduced nicotinamide adenine dinucleotide (NADH)-as cancer biomarkers. S3 combines both fluorescence and absorption spectra in one scan. The S3 spectra were analyzed using machine learning (ML) algorithms, including principal component analysis (PCA), nonnegative matrix factorization (NMF), and support vector machines (SVMs). The components retrieved from the S3 spectra were considered principal biomarkers. The differences in the weights of the components between the two types of tissues were found to be significant. Sensitivity, specificity, and accuracy were calculated to evaluate the performance of SVM classification. This research demonstrates that S3 spectroscopy is effective for detecting the changes in the relative concentrations of the endogenous fluorophores in tissues due to the development of cancer label free.

Diterpenoid alkaloids from Delphinium trichophorum.

Three new hetisine type C20-diterpenoid alkaloids, named as trichophorines A-C (1-3), were isolated from Delphinium trichophorum, together with nine known alkaloids (4-12). Their structures were elucidated on the basis of spectroscopic data (1D, 2D NMR, single-crystal X-ray, and HR-ESI-MS). All compounds were evaluated for the inhibitory activities against LPS induced NO production in RAW 264.7 macrophage cells, and none of them showed considerable inhibitory activity.

Longitudinal relationship between quality of life and negative life events among adolescents during COVID-19 pandemic: a cross-lagged panel analysis.

BACKGROUND: The negative association of quality of life (QoL) and negative life evens (NLEs) among adolescents has been proved by cross-sectional studies, without exploring sex differences. This study aimed to explore the longitudinal associations between QoL and NLEs among adolescents during novel coronavirus disease 2019 (COVID-19) pandemic and whether there are sex or age differences. METHODS: A stratified cluster sampling was used to select 1421 students in primary school and middle school in Chongqing, China. From November 2020 (T0) to December 2021 (T2), the Adolescent Self-Rating Life Events Checklist and the Adolescent Quality of Life Scale were used to collect 3 waves of data. The correlations between study variables were conducted by the Pearson correlation analyses. The direction and strength of the longitudinal associations were analyzed using cross-lagged panel analyses. RESULTS: Results showed significant changes in both variables during COVID-19 pandemic (P < 0.001). Cross-sectional analyses showed stable negative correlations between NLEs and QoL stratified by sex or by age (P < 0.001). Sex and age differences in longitudinal relationships were shown by cross-lagged panel analyses. For males, NLEs had a short-term bi-directional association with QoL [ßA-D = -(0.091-0.340), P < 0.05]; for females, QoL had a short-term correlation with NLEs [ßA = -0.119), ßC = -0.109), P < 0.001]. In the youngest age group, NLEs had a short-term bi-directional correlation with QoL [ßA-D = -(0.098-0.428), P < 0.05]. There was a short-term association between total QoL and NLEs among students except the 14∼15 year group [ßA = -(0.071-0.149), ßC = -(0.086-0.119), P < 0.05], the long-term association between total QoL and NLEs was only significant in adolescents aged 14∼15 years (ßE = -0.132, P < 0.05). The strength of NLEs was slightly higher than that of total QoL, but lower than that of QoL in each dimension. CONCLUSION: There were negative longitudinal relationships between NLEs and QoL during COVID-19 pandemic, and the strength of the associations varied across sex or age. Strengthening QoL in different dimensions may be a promising way to reduce NLEs during the pandemic among adolescents, and interventions should be tailored according different sex and ages.

[Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota].

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1ß, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Inhibiting α1-adrenergic receptor signaling pathway ameliorates AD-type pathologies and behavioral deficits in APPswe/PS1 mouse model.

The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer's disease (AD) has rarely been investigated. Clarifying the pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic targets of AD. This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (α1-ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or an equal volume of saline for 6 months. SH-SY5Y cell lines bearing human amyloid precursor protein were treated with terazosin or saline for investigating possible mechanisms. α1-ARs knockdown mice exhibited improved behavioral performances in comparison with control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aß species, compact and total Aß plaques, than control mice. α1-ARs inhibitor terazosin substantially reduced Aß deposition, attenuated downstream pathologies including tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction et al., and rescued behavioral deficits in APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3ß, thus reducing Aß production. This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.

Establishment of Minimal Clinically Important Improvement for Patient-Reported Symptoms to Define Recovery After Video-Assisted Thoracoscopic Surgery.

PURPOSE: The aim of this study was to define a threshold of minimal clinically important improvement (MCII) for interpreting patient condition following video-assisted thoracoscopic surgery (VATS). METHODS: Patients undergoing VATS were recruited for this multicenter, prospective, observational cohort study. Symptoms were measured using the MD Anderson Symptom Inventory-Lung Cancer Module perioperatively. To define MCIIs, we first identified index symptoms, defined as the most severe symptoms showing the largest reduction from day 1 post-surgery to discharge. MCIIs for each index symptom were then obtained via an anchor-based approach. Symptom recovery was defined as an MCII after post-surgery day 1. Cox regression models were used to identify risk factors for unrecovered index symptoms. RESULTS: Using 366 patients, we identified pain and fatigue as index symptoms after VATS. MCII was defined as a 30% reduction in pain or fatigue. At discharge, 22.6% of patients had not recovered from pain and 22.4% had not recovered from fatigue. Cox models found that risk factors for unrecovered pain were Charlson Comorbidity Index score ≥1 (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.04-1.77; p = 0.02) and preoperative neoadjuvant therapy (HR 2.78, 95% CI 1.13-6.83; p = 0.02). Malignancy was a risk factor for unrecovered fatigue (HR 1.47, 95% CI 1.02-2.13; p = 0.04). CONCLUSION: Pain and fatigue can be used as index measures for symptom recovery in patients following VATS. A 30% MCII represented meaningful recovery after VATS and could identify patients who may need extensive care after discharge.

Blood cell-produced amyloid-ß induces cerebral Alzheimer-type pathologies and behavioral deficits.

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

Discrepancy in the perception of symptoms among patients and healthcare providers after lung cancer surgery.

PURPOSE: Patients who undergo surgery for lung cancer experience a variety of symptoms, such as pain and coughing, which interfere with their postoperative daily functions. However, there may be differences between the perception of symptoms among healthcare providers and patients. This study aimed to investigate patients' experiences after lung cancer surgery and analyze whether the perception of postoperative symptoms among the healthcare providers differed from that reported by patients. METHODS: Semi-structured qualitative interviews involving 39 patients who underwent lung cancer surgery at the Sichuan Cancer Hospital were conducted between November 2018 and October 2019. In addition, 22 healthcare providers from the Department of Thoracic Surgery at the hospital answered open-ended questions about their perception of symptoms related to lung cancer surgery. The types and frequencies of symptoms reported by the patients and healthcare providers were compared. RESULTS: The most frequent patient-reported symptoms were pain (967 times, 39 patients, 100%), coughing (904 times, 37 patients, 94.87%), shortness of breath (491 times, 35 patients, 89.74%), Disturbed sleep (412 times, 34 patients, 87.18%), and interference while walking (347 times, 36 patients, 92.31%). Of the patient-reported symptoms, the first four were perceived by the healthcare providers, while they interpreted interference while walking as fatigue. CONCLUSION: Although the healthcare providers and patients had a certain consensus on the main symptoms, there were differences in perception. Healthcare providers need to pay more attention to postoperative interference while walking.

The association between pubertal timing and quality of life among children and adolescents: a cross-sectional study in Chongqing, China.

BACKGROUND: To determine the relationship between pubertal timing and quality of life (QOL) in children and adolescents and to provide a basis for QOL intervention in pubertal children in the future to promote good adaptation and healthy physical and mental development of children. METHODS: The survey was conducted in one county using a stratified cluster sampling method. The five physiological change items of the Puberty Development Scale (PDS) were used to assess the timing of puberty in students. Compared to students of the same age and the same sex, students who scored higher than the mean + standard deviation (SD) of individual developmental scores were defined as an early pubertal timing group. A 39-item QOL Scale for Children in Puberty was used to assess the QOL of the respondents. Multiple linear regression models were fitted separately for boys and girls. RESULTS: Of the 7223 students, 3754 (51.97%) were boys and 3469 (48.03%) were girls. The prevalence of early pubertal periods was 16.07%. The total QOL score in the early pubertal timing group (137.16 ± 18.67) was significantly lower than in the normal (on time) group (142.02 ± 17.98) and the late group (142.76 ± 18.35) (F = 37.311, P < 0.001). A multiple linear regression model showed that early pubertal timing was a risk factor for QOL (P < 0.0014), compared with normal and late pubertal timing. CONCLUSIONS: The early pubertal timing was associated with poorer QOL in children and adolescents. More attention should be paid to children with early pubertal timing in intervening children's QOL during pubertal development. Future longitudinal studies are needed to confirm the association between pubertal timing and QOL.

[Relationship between unhealthy weight loss and depressive symptoms among adolescents in Chongqing City].

OBJECTIVE: To investigate the relationship between unhealthy weight loss behaviors and depressive symptoms among adolescents in Chongqing. METHODS: From October to November in 2019, 4 urban combined junior and senior high school and 4 rural combined junior and senior high school in Chongqing were selected by stratified cluster sampling method, and the unhealthy weight loss behavior questionnaire and the center for epidemiological studies depression scale(CES-D scale) were used to investigate the weight loss behavior and depression symptoms of junior one to senior three students. A total of 3969 subjects were enrolled, including 1479(37.26%) males and 2490(62.73%) females. Chi-square test was used to analyze the relationship between general demographic characteristics and depressive symptoms, and binary Logistic regression model was used to analyze the relationship between unhealthy weight loss behavior and depressive symptoms. RESULTS: Among the 3969 subjects, 2972(74.88%) reported unhealthy weight loss behaviors, and 1459(36.76%) had depressive symptoms. There were significant differences in depressive symptoms among adolescents with different gender(χ~2=34.83, P<0.01), school type(χ~(2 )=6.75, P<0.01), father's parenting style(χ~2=159.64, P<0.01), mother's parenting style(χ~2=160.10, P<0.01), family economic conditions(χ~2=63.88, P<0.01), learning pressure(χ~2=207.53, P<0.01), number of close friends(χ~2=177.52, P<0.01)and number of school health education classes(χ~2=31.60, P<0.01). Binary Logistic regression analysis showed that unhealthy weight loss behavior was a risk factor for depressive symptoms(OR=1.436, P<0.01), and unhealthy weight loss level was positively correlated with the prevalence of depressive symptoms(OR>0, P<0.01). CONCLUSION: There was a positive correlation between unhealthy weight loss behavior and depressive symptoms among adolescents in Chongqing.

[Research progress on precious Tibetan medicine formula in prevention and treatment of central nervous system diseases].

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.