Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

To address the challenges in blood cell recognition caused by diverse morphology, dense distribution, and the abundance of small target information, this paper proposes a blood cell detection algorithm - the "You Only Look Once" model based on hybrid mixing attention and deep over-parameters (HADO-YOLO). First, a hybrid attention mechanism is introduced into the backbone network to enhance the model's sensitivity to detailed features. Second, the standard convolution layers with downsampling in the neck network are replaced with deep over-parameterized convolutions to expand the receptive field and improve feature representation. Finally, the detection head is decoupled to enhance the model's robustness for detecting abnormal cells. Experimental results on the Blood Cell Counting Dataset (BCCD) demonstrate that the HADO-YOLO algorithm achieves a mean average precision of 90.2% and a precision of 93.8%, outperforming the baseline YOLO model. Compared with existing blood cell detection methods, the proposed algorithm achieves state-of-the-art detection performance. In conclusion, HADO-YOLO offers a more efficient and accurate solution for identifying various types of blood cells, providing valuable technical support for future clinical diagnostic applications.
Algorithms ; Humans ; Blood Cells/cytology* ; Blood Cell Count/methods* ; Neural Networks, Computer ; Deep Learning ; Detection Algorithms

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

OBJECTIVE: The role of cold spells of different intensities in the economic burden of death is crucial for health adaptation to climate change, especially in a multi-site setting. The objective of the study was to explore the economic burden of mortality attributable to cold spells. METHODS: We performed a two-stage time-series analysis using the Value of Statistical Life (VSL) approach to evaluate the economic impact of mortality related to cold spells of varying lengths and intensities. This analysis employed a case-crossover design, with a distributed lag nonlinear model (DLNM) used for analysis. Analysis was stratified according to age, sex, and region of origin. The results of the assessment show that cold spells have an enormous impact on the economic losses of mortality due to climate change and aging. RESULTS: Totally, 8.3% (95% CI: 0.0%, 16.0%) to 13.8% (95% CI: 1.0%, 24.8%) of VSL were ascribed to cold spells, accounting for economic losses of 4.71 (95% CI: 0.34, 8.47) to 11.45 (95% CI: 0.00, 21.00) billion CNY, in the cold season. The population aged over 65 y and females are particularly vulnerable. Economic impacts in warmer regions, such as the southern and subtropical zones, are more extensive than those in the northern and temperate zones. CONCLUSION Customizing cold spell prevention measures for vulnerable populations or regions is vital to alleviating the socioeconomic burden.
China/epidemiology* ; Humans ; Female ; Male ; Cold Temperature/adverse effects* ; Aged ; Middle Aged ; Adult ; Mortality ; Infant ; Child ; Adolescent ; Child, Preschool ; Young Adult ; Climate Change ; Aged, 80 and over ; Cost of Illness ; Infant, Newborn

OBJECTIVE To investigate the effects of 3 different primitives or the same primitives with different characters of Tibetan medicine Zuomoxing[Caragana changduenais Liou f. with red heartwood, Caragana jubata(Pall.) Poir. with brown and white heartwood] on rats with pattern of toxic heat-induced blood stasis. METHODS　Ninety SD rats were randomly divided into the blank group, model group, aspirin-positive group, Changdu low-dose group(CDD), Changdu high-dose group(CDG), whitewood of Guijian low-dose group(GJBD), whitewood of Guijian high-dose group(GJBG), brown wood of Guijian low-dose group(GJZD), Brown wood of Guijian high-dose group(GJZG). Models with heat toxicity and blood stasis pattern were established by intraabdominal injection of carrageenan combined with tail vein injection of lipopolysaccharide. The effects of each group on blood rheology, coagulation four indices and blood routine were determined, and the content of arachidonic acid(AA), IL-1β, IL-6, TNF-α and thromboxane B2(TXB2) were measured with ELISA. RESULTS ①Blood rheology: Compared with model group, CDD and CDG significantly decreased whole blood viscosity(WBV), reduction viscosity of whole blood(WBRV), erythrocyte rigidity index(HGX), erythrocyte deformability index(EDI), whole blood relative index(WBRI) (P<0.01), and increased plasma viscosity(P<0.01). GJZG and GJZD significantly decreased HGX(P<0.01 or P<0.05), and increased plasma viscosity(P<0.01). GJBG and GJBG significantly decreased WBHSV, WBHSRV, HGX, EDI, and whole blood high shear relative index(WBHSRI)(P<0.01). ②Coagulation four indices: Compared with model group, CDD significantly reduced the thrombin time(TT)(P<0.01). GJZG significantly reduced activated partial thromboplastin time(APTT) and TT(P<0.01 or P<0.05). GJBD significantly reduced prothrombin time(PT) and APTT (P<0.01 or P<0.05). ③Blood routine: Compared with model group, GJZD and GJBD significantly decreased the percentage of monocytes(P<0.01 or P<0.05). The number of large platelets in CDD significantly increased(P<0.05). CDG significantly increased the platelet number, platelet hematocrit, and large platelet number(P<0.01 or P<0.05), and tended which to be normal. ④Inflammatory factors: Compared with model group, the levels of TNF-α, IL-6, TXB2 were significantly increased in CDD and CDG(P<0.01 or P<0.05). The levels of IL-6 and TXB2 were significantly increased in GJZD and GJZG(P<0.01). GJBD was significantly increased TXB2(P<0.01), and GJBG was significantly increased IL-1β, IL-6, and TXB2(P<0.01), while decreased AA(P<0.05). CONCLUSION Zuomoxing with separate sources have different degrees of effects on rats with pattern of toxic heat-induced blood stasis, and have different degrees of effects on hemorheology, coagulation factors, blood routine and inflammatory mediators, and the degree and trend of effects are different with different doses. The effect of promoting blood circulation and removing blood stasis was generally manifested as Changdu > whitewood of Guijian > Brown wood of Guijian. The effect of promoting blood circulation and removing blood stasis may be the result of multiple pathways and mechanisms.

Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P＜0.001;r=0.466,P＜0.001);ADL was positively correlated with sleep quality(r=0.294,P＜0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P＜0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.

Based on WANG Xugao's “thirty methods of treating the liver”， it is believed that the occurrence and development of childhood tic disorders follow the dynamic progression from liver qi disease to liver fire disease and then liver wind disease. The basic pathogenesis of three stages are characterized by binding constraint of liver qi， liver fire hyperactivity， and internal stirring of liver wind. Moreover， liver-blood deficiency and stagnation， and malnutrition of liver yin as the main point in terms of the imbalance of liver qi， blood， yin， and yang should be considered， as well as the imbalance relationship of the five zang organs such as the involvement of other organs and the gradually reach of the other organs. Guided by the principles of “thirty methods of treating the liver”， the treatment of tic disorders in liver qi stage should focus on soothing the liver and rectifying qi， soothing the liver and unblocking the collaterals， using Xiaochaihu Decoction （小柴胡汤） and Sini Powder （四逆散）. The treatment of tic disorders in liver fire stage involves clearing， draining and resolving liver heat， using Longdan Xiegan Decoction （龙胆泻肝汤）， Xieqing Pill （泻青丸）， Danggui Longhui Pill （当归龙荟丸）， and Huagan Decoction （化肝煎）. The treatment of tic disorders in liver wind stage involves extinguishing wind and subduing yang， using Lingjiao Gouteng Decoction （羚角钩藤汤） and Liuwei Dihuang Pill （六味地黄丸）. Throughout the treatment process， attention should be paid to harmonizing the liver's qi， blood， yin， and yang， as well as addressing the pathology of other organs.

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.