ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P0.05）， and compared with the model group， both were significantly increased in the Sini San group （P0.05， P0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P0.05， P0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P<0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P<0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P<0.05）， and compared with the model group， both were significantly increased in the Sini San group （P<0.05， P<0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P<0.05， P<0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P<0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

Objective To analyze the epidemiological characteristics and spatial-temporal clustering trend of scarlet fever in Nantong from 2009 to 2023, and to provide a scientific basis for scarlet fever prevention and control. Methods The incidence data of scarlet fever in Nantong from 2009 to 2023 were analyzed. Descriptive analysis, seasonal index method and Joinpoint 5.2.0 software were used to analyze epidemiological characteristics. Spatial-temporal clustering was assessed with SaTScan 10.2.5 software. Results The average annual incidence of scarlet fever in Nantong from 2009 to 2023 was 6.54/100 000. The overall morbidity rate of scarlet fever in Nantong had an increasing trend from 2009 to 2019 with an average annual percentage change of 14.55% (t=3.36，P<0.05). The cases mainly occurred during late spring to early summer and late autumn to early winter. Students, preschool children and scattered children were the main scarlet fever population. The average annual incidence of males was significantly higher than that of females (χ²=7.00, P<0.05). Rugao City, Chongchuan District and Tongzhou District were identified as high-incidence areas, accounting for 76.51% of all reported cases. Spatial-temporal scan analysis indicated that Rugao City and Chongchuan District were primary cluster areas, spanning from 2015 to 2021 (RR=3.77, LLR=1 308.07, P<0.05). Conclusion The number of reported cases of scarlet fever in Nantong City from 2009 to 2023 shows epidemic and spatial clustering, mainly concentrated in the central urban area and adjacent counties (cities). It is necessary to strengthen health education and disease surveillance in high-incidence areas, as well as in key institutions and key populations before epidemic peaks.

Objective: To evaluate the intervention efficacy of integrated group social skills training on social ability in school age patients with high functioning ASD, so as to provide a reference for improving social skills in children with high functioning ASD. Methods: From January 2021 to December 2023, 62 children aged 7-12 with high functioning ASD who visited the Children s Psychiatry Outpatient Department of the Affiliated Kangning Hospital of Ningbo University were recruited, and were randomly divided into a training ( n =31) and a control group ( n =31) by a random number table method. The training group received a 20 week structured group social training program (mental interpretation courses and social courses), while the control group received only conventional treatment. Chinese version of Griffith Empathy Measure Parent Ratings (GEM-PR) and Social Response Scale (SRS) were used to assess the symptoms of social deficits before and after treatment. Emotional face recognition tasks and eye movement trajectories were used to test the characteristics of social visual attention in children with ASD. Group comparison was conducted using t-test and Mann-Whitney U test. Results: At baseline, there were no significant differences in GEM-PR score ( t = -1.20 to -0.81), SRS score ( t =-0.36-1.75), emotional face recognition accuracy and reaction time ( t =-0.58-1.85), and eye movement trajectory ( U/t =-1.63-0.29) between the two group ( P >0.05). After intervention, the total GEM-PR score and empathic cognitive factor score of training group [18.00(10.00，24.00)，9.00(8.00，13.00)] were significantly higher than those of the control group [12.00(-1.00，18.00)，2.00(-2.00，7.00)], and the total SRS score and social cognition, social perception, social communication, social motivation (73.23±14.20, 16.16±2.72, 6.58±2.50, 24.29±5.61, 9.52±3.73) were significantly lower than those of the control group (95.26±15.29, 19.90±2.84, 12.58±2.49,31.94±6.38, 13.74±4.81) ( U/t =-2.38, -4.59; -5.88, -5.29, -9.47, -5.01, -3.87, P <0.05). The overall correct rate of emotional face recognition and the correct rate of angry, fearful and neutral faces recognition in the training group [(81.55±6.62)%，(76.86±12.06)%，(79.61±12.42)%，(94.27±6.26)%] were significantly higher than the control group [(70.55±13.82)%，(62.82±18.77)%，(67.18±18.85)%，(79.60±20.05)%], and the average reaction time [(2 226.70±274.43)ms] was lower than the control group [(2 417.27±324.10)ms] (t=4.00, 3.50, 3.07, 3.89, -2.42, P<0.05). The time to first eye gaze [764.74 (748.64, 793.73) ms] in the training group was significantly lower than that in the control group [810.92 (782.86, 877.42) ms], and the proportion of moderatetohigh intensity attention area in the face [(37.37±1.27)%] was significantly higher than that in the control group [(30.34±1.23)%] (U/t=3.44, 8.89, P<0.05). Conclusion Integrated group social training can significantly improve the social communication and empathy ability of high functioning ASD children, increase active attention and recognition ability of faces, and improve mental development of children with ASD.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Objective:To analyze the main chemical components of Lanqin Granules based on UPLC-Q-TOF-MS/MS; To explore the potential targets, core components and related pathways of Lanqin Granules in the treatment of respiratory tract infection through network pharmacology.Methods:Using UPLC-Q-TOF-MS/MS secondary fragment cleavage information, combined with literature and database, the chemical components of Lanqin Granules were analyzed; the related action targets of Lanqin Granules were obtained by PharmMapper; The related targets of respiratory tract infection were obtained from GeneCards and OMIM databases, and the common targets were selected by intersection with the relevant action targets of Lanqin Granules. The common targets were imported into string database, and the protein interaction data were downloaded and input into Cytoscape 3.7.2 software to obtain hub gene; Go function and KEGG pathway enrichment analysis were carried out on DAVID platform, and chemical components closely related to hub gene were obtained by using the Network Anlyzer plug-in.Results:53 chemical constituents of Lanqin Granules were obtained, including 11 alkaloids, 20 flavonoids, 5 terpenoids, 7 organic esters, 2 amino acids and 8 other compounds. 28 hub genes and 38 related core components were obtained. The results of GO analysis showed that the treatment of respiratory tract infection with Lanqin Granules was related to neutrophil degranulation, negative regulation of apoptosis, protein hydrolysis and other biological processes; extracellular exosomes, cytoplasm, extracellular components and other cellular components; the same protein binding, RNA polymerase Ⅱtranscription factor activity, ligand activated sequence specific DNA binding, protein serine/ threonine/ tyrosine kinase activity and other molecular processes. KEGG analysis results mainly involved cancer pathway, lipid and atherosclerosis, metabolic pathway and other signaling pathways.Conclusion:Lanqin Granules can treat respiratory tract infection through multi-component, multi-target and multi-channel, and play the role of anti-inflammatory, antibacterial and anti-virus.

Objective Melatonin has been shown to have neuroprotective effects.This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk(TX)mouse model of Wilson disease(WD),and investigating the effects and mechanisms of action of Gandou Bushen Decoction(GDBSD)on melatonin synthesis and pineal function in the WD model mice.Methods A total of 30 homozygous TX mice were randomly assigned to 3 groups(n=10 in each group),including a WD group,a GDBSD group,and a dimercaptosuccinic acid(DMSA)group.A total of 10 DL mice were included in the normal control(NC)group.The structure and copper content of pineal gland tissues,oxidative stress and apoptosis-related markers,and serum melatonin levels were evaluated using hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),flow cytometry,and Western blot.Results Compared with the NC group,the WD group exhibited decreased learning and cognitive abilities(P＜0.05),damaged pineal gland structure,increased copper content,reactive oxygen species(ROS)levels,and mitochondrial damage rate in the pineal gland(P＜0.01),altered levels of melatonin and oxidative stress-related markers(P＜0.05),upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3,and decreased expression of the anti-apoptotic protein Bcl-2(P＜0.01).After treatment with GDBSD and DMSA,the SIRT3/FOXO3α signaling pathway was activated,the copper content in the pineal gland was reduced,and oxidative stress and apoptosis-related damages were improved,leading to an improvement in learning and memory abilities(P＜0.05).Conclusion GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland.The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.

Objective To investigate the effect of Xuefu Zhuyu Decoction combined with external counterpulsation therapy on angina pectoris attacks and brachial artery flow-mediated dilation(FMD)in patients with angina pectoris of heart blood stasis syndrome.Methods A total of 80 patients with stable coronary artery disease(SCAD)and angina pectoris who visited our hospital between March 2022 and December 2023 were selected as study subjects and randomly divided into control group(40 cases)and treatment group(40 cases).The control group received conventional treatment and Xuefu Zhuyu Decoction,while the treatment group received external counterpulsation therapy in addition to the control group's treatment.The angina pectoris attacks before and after treatment in both groups was recorded.Color Doppler ultrasound was used to measure brachial artery FMD;electrocardiogram was used to measure heart rate variability indicators,including the standard deviation of the average of normal to normal intervals(SDANN)for 5 consecutive minutes,standard deviation of normal to normal intervals(SDNN),and square root of the mean of the sum of the squares of the differences between consecutive N-N intervals(rMSSD).A fully automatic biochemical analyzer was used to measure blood lipid indicators such as high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),and triglycerides(TG).Nitrate reductase method was used to detect serum nitric oxide(NO)levels,and enzyme-linked immunosorbent assay(ELISA)was used to detect serum endothelin-1(ET-1)levels.Adverse events in both groups were recorded.Results After treatment,the attack frequency of angina pectoris decreased and duration shortened in both groups compared with before treatment,and the attack frequency of angina pectoris was lower and duration shorter in the treatment group than in the control group(P＜0.05).After treatment,FMD and NO levels increased,and ET-1 levels decreased in both groups compared with before treatment,and FMD and NO levels were higher,while ET-1 levels were lower in the treat-ment group than in the control group(P＜0.05).After treatment,SDANN,SDNN,and rMSSD in-creased in both groups compared with before treatment,and SDANN,SDNN,and rMSSD were higher in the treatment group than in the control group(P＜0.05).After treatment,HDL-C levels in-creased,while LDL-C,TC,and TG levels decreased in both groups compared with before treatment,and HDL-C levels were higher,while LDL-C,TC,and TG levels were lower in the treatment group than those in the control group(P＜0.05).No serious adverse reactions occurred during treatment in both groups,and vital signs were normal,with normal liver and kidney function.Conclusion Xuefu Zhuyu Decoction combined with external counterpulsation can effectively alleviate clinical symptoms,reduce the frequency of angina pectoris attacks,shorten the duration of angina pectoris,improve brachial artery FMD,endothelial function,heart rate variability,and blood lipid levels in patients with angina pectoris of heart blood stasis syndrome.Besides,it has higher safety.