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

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To explore the application effect of ICU nursing sub-specialty management model in the clinical treatment of ICU patients.Methods:Based on the actual needs of ICU patients,a precise and systematic management plan including organizational structure,workflow,linkage mechanism,quality control system,dynamic follow-up,and scientific research transformation was formulated,to construct a working model of multi-linkage,multi-direction supplement and coordinated development of two-way feedback mechanism in sub-specialty nursing.The control group was set before the implementation of ICU nursing sub-specialty management mode(Jan 1 to Dec 31,2021),and the intervention group was set after the implementation of ICU nursing sub-specialty management model(Jan 1 to Dec 31,2022).The core competence,specialty,sensitive indicators,satisfaction,and impact on patients were compared before and after implementation.Results:After the implementation of the ICU nursing sub-specialty management model,the core competence of nurses was improved,and the hospitalization time and mechanical ventilation time of patients were reduced,the incidence of re-entry ICU,acquired weakness,acquired dysphagia and incontinence dermatitis was decreased,the proportion of unplanned extubation was decreased,and the satisfaction of patients,nurses,doctors and students was improved(P＜0.05).Conclusion:The construction of ICU nursing sub-specialty management model can effectively promote the construction of ICU nursing sub-specialty,improve the core competence of nurses,reshape the connotation of nursing,improve the prognosis of patients,and ultimately promote the benign and sustainable development of hospital nursing.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Here,5 important pathogens carried by ticks in Maanshan City,Anhui Province,China were identified.In to-tal,642 ticks were collected from 13 villages around Maanshan City and identified by morphological and mitochondrial COI genes.The 16S rRNA gene of Francisella tularensis,ssrA gene of Bartonella,16S rRNA,ompA and ompB genes of Rickett-sia,16S rRNA and gltA genes of Anaplasma,and groEL and rpoB genes of Coxiella were sequenced.Reference sequences were retrieved from a public database.Phylogenetic trees were constructed with MEG A1 1.0 software.In total,36 Rickettsiae isolates were detected in 640 Haemaphysalis longicornis ticks,which included 20 isolates of Rickettsia heilongjian-gensis,16 of Candidatus Rickettsia jingxinensis,2 of Ana-plasma bovis,and 186 of Coxiella-like endosymbiont.R.hei-longjiangensis HY2 detected in this study and Anhui B8 strain,Ca.R.jingxinensis QL3 and those from Shanxi Prov-ince and Jiangsu Province,A.bovis JX4 and those from Shanxi Province were clustered on the same branch.Overall,17 ticks had combined infections and none of the 5 bacteria were detected in two Amblyomma testudinarium ticks.This is the first report of Ca.R.jingxinensis detected in H.longicornis ticks from Anhui Province.It is recommended that the two types of Rickettsia that cause spotted fever and A.bovis should be reported to local health authorities to initiate appropriate prevention and control measures.

Cancer pain is one of the most common symptoms in patients with advanced cancer. In this study, we aimed to investigate the effects of the Mas-related gene C (MrgC) receptors on bone cancer pain. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured after the inoculation of Walker 256 mammary gland carcinoma cells into the tibia of adult Sprague-Dawley rats. The effects of MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) on nociceptive behaviors were investigated after intrathecal injection on days 16 and 17. Glial fibrillary acidic protein (GFAP)-positive cells in the spinal dorsal cord, and calcitonin gene related peptide (CGRP)-, neuronal nitric oxide synthase (nNOS)- and IL-1β-positive neurons in the dorsal root ganglia (DRG) were examined by immunofluorescence staining. The expression of nNOS and IL-1β proteins in the spinal dorsal horn and the DRG was examined by Western blotting after treatment with (Tyr6)-γ2-MSH-6-12 (MSH), which was another MrgC receptor agonist. The results showed that intrathecal injection of BAM8-22 (30 nmol) attenuated mechanical allodynia in a rat model of bone cancer pain and the effects could last for about 60 min, and single administration of BAM8-22 for two consecutive days reduced mechanical allodynia by about half on the third day. Moreover, the number of GFAP-positive cells in the spinal dorsal horn, and the number of CGRP-, nNOS- and IL-1β-positive neurons in the DRG were decreased. Similarly, intrathecal administration of MSH (15 nmol) reduced the expression of nNOS and IL-1β in the spinal dorsal horn and the DRG. In conclusion, activation of MrgC receptors suppresses the activation of astrocytes in the spinal dorsal cord and the expression of CGRP, nNOS, and IL-1β in the spinal dorsal cord and/or DRG, which may underlie the inhibition of bone cancer pain. These findings provide a novel strategy for the treatment of bone cancer pain.
Animals ; Cancer Pain/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Bone Neoplasms/complications* ; Ganglia, Spinal/metabolism* ; Spinal Cord Dorsal Horn/metabolism* ; Receptors, G-Protein-Coupled/genetics* ; Female ; Calcitonin Gene-Related Peptide/genetics* ; Interleukin-1beta/metabolism* ; Peptide Fragments/metabolism* ; Nitric Oxide Synthase Type I/genetics* ; Disease Models, Animal