ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

Objective To investigate the cross-sectional associations between different fatty liver classifications and cardiac structure and function in people undergo health examination. Methods A total of 6 545 adults who underwent health examinations at the Health Management Center of Zhongshan Hospital, Fudan University between January 1 and December 31, 2017, were retrospectively included. Demographic characteristics and laboratory data were collected. The hepatic steatosis was graded by ultrasonography. And patients with fatty liver were further stratified according to alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, as well as the degree of liver fibrosis. Cardiac morphology and function were assessed by transthoracic echocardiography, and left ventricular geometric patterns were classified accordingly. Multivariate logistic regression analysis was performed to evaluate the associations between fatty liver classifications and cardiac abnormalities. Results There were 2 795 patients (42.7%) with fatty liver, of whom 832 (29.8%) had significant cardiac structural alterations and 1 500 (53.7%) had diastolic dysfunction. Severe fatty liver was risk factor for concentric remodeling and increased relative wall thickness (RWT), with odds ratios (ORs) of 1.27 (P＝0.012) and 1.27 (P＝0.009), respectively. Fatty liver accompanied by elevated ALT or AST was risk factor for concentric remodeling (OR＝1.45,1.56; P＝0.001, 0.001), increased RWT (OR＝1.48,1.57; P＜0.001, ＜0.001), and diastolic dysfunction (OR＝1.27, 1.32; P＝0.035, 0.040), respectively. Fatty liver with liver fibrosis was risk factor for concentric remodeling (OR＝1.83, P＝0.046) and diastolic dysfunction (OR＝2.64, P＝0.034). Conclusions Advanced fatty liver, including severe hepatic steatosis, accompanied by elevated liver enzymes or liver fibrosis, could increase risks of cardiac remodeling and diastolic dysfunction, while systolic function is preserved. For patients with fatty liver, it is recommended to undergo regular ultrasonography examination.

ObjectiveTo investigate whether intestinal deficiency of lanosterol synthase （LSS）， a key enzyme in cholesterol synthesis， influences the progression of metabolic dysfunction-associated steatotic liver disease （MASLD） by regulating intestinal cholesterol absorption and immune response. MethodsLSS heterozygous knockout （LSS^+/-） mice and wild-type （WT） controls were generated using CRISPR/Cas9 technology and fed either a high-fat diet （HFD） or regular chow （CHOW）. The model was validated by genotyping. Hepatic steatosis was assessed by HE and oil red O staining. Immunohistochemistry was used to detect the localization and expression of NPC1L1 and CD36 proteins in the intestine. Western blot analysis was performed to measure JNK phosphorylation and TLR4 protein levels in intestinal tissues. Real-time quantitative polymerase chain reaction （qPCR） was employed to examine the mRNA expression of TLR4 and IL-6. ResultsLSS^+/- mice were successfully validated by genotyping and reduced intestinal LSS protein expression. HE and oil red O staining of liver sections showed that， compared with WT mice fed a CHOW diet， WT mice fed a HFD exhibited a marked increase in hepatic lipid vacuoles. In contrast， compared with HFD-fed WT mice， HFD-fed LSS^+/- mice displayed significantly attenuated hepatic lipid deposition and reduced serum ALT levels （P<0.05）. Immunohistochemical analysis revealed that， compared with WT mice， the expression of the cholesterol absorption protein NPC1L1 in the intestinal villi of LSS^+/- mice was downregulated under both CHOW and HFD conditions （P_HFD<0.001）. Conversely， the expression of the fatty acid transporter CD36 was upregulated in the intestines of LSS^+/- mice （P_CHOW<0.05， P_HFD<0.01）. Western blot analysis demonstrated that， compared with WT mice， TLR4 protein expression in the intestines of LSS^+/- mice significantly increased under both CHOW and HFD conditions （both P<0.05）. JNK phosphorylation level was significantly elevated in LSS^+/- mice under CHOW condition （both P<0.05）. Under HFD condition， total JNK protein expression increased， but its phosphorylation level showed no significant change. qPCR analysis showed that， compared with WT mice， the mRNA levels of TLR4 （P_CHOW<0.01， P_HFD<0.000 1） and IL-6 （P_CHOW<0.001， P_HFD<0.01） were significantly upregulated in the intestines of LSS^+/-mice. ConclusionLSS deficiency counteracts hepatic lipid deposition by orchestrating a synergistic reprogramming involving restricted intestinal cholesterol absorption， enhanced fatty acid utilization， and activation of immune pathways， suggesting intestinal LSS as a potential therapeutic target of MASLD.

Objective To investigate the correlations of interleukin-1 β(IL-1β)level and per-centage of CD16+CD56+natural killer(NK)cells in peripheral blood with severity of disease in pa-tients with pulmonary tuberculosis.Methods A total of 150 patients with active pulmonary tubercu-losis(APTB)in the Suqian First People's Hospital from January 1,2021 to September 1,2023 were selected as APTB group,and 150 patients with inactive pulmonary tuberculosis(IPTB)in the same period were selected as IPTB group.Level of IL-1 β and percentage of CD16+CD56+NK cells in pe-ripheral blood of patients with different disease severities were compared,and their correlations with severity of disease were analyzed.Results In the APTB group,level of IL-1 β in the peripheral blood was significantly higher than that in the IPTB group,while the percentage of CD16+CD56+NK cells was significantly lower(P＜0.001).In the mild,moderate,and severe groups,level of IL-1 βshowed a significant gradual increasing trend in peripheral blood,while the percentage of CD16+CD56+NK cells showed a significant gradual decreasing trend(P＜0.001).After treatment,the level of IL-1β in the peripheral blood decreased significantly,while the percentage of CD16+CD56+NK cells increased significantly in the APTB group(P＜0.001).Correlation analysis revealed that level of IL-1β in the peripheral blood of patients with pulmonary tuberculosis was positively correlated with severity of disease(r=0.732,P＜0.001),while the percentage of CD16+CD56+NK cells was negatively correlated with severity of disease(r=-0.612,P＜0.001).Conclusion Level of IL-1β in the peripheral blood is elevated while the percentage of CD16+CD56+NK cells is de-creased in patients with pulmonary tuberculosis,which is closely related to the severity of APTB.

Objective : To explore the changes in behavior and spatial memory of C57BL/6J female mice of different ages (youth , middle-aged , and elderly) . Methods: C57BL/6J female mice were divided into female youth group (YG group) , female middle-aged group ( MG group) and female elderly group ( OG group) according to age. The Morris water maze test measured spatial memory ability , and the open field and elevated cross maze test observed activity level and anxiety level. Western blot was used to determine the protein expressions of CREB , CaMKⅡ(pan) and CaMKⅡ(p) in the hippocampus of the brain tissues of female mice in each group. Results: Compared with the YG group , the weight of the MG group and the OG group significantly increased (P < 0. 01 , P < 0. 001) . Compared with the OG group , the third quadrant escape latency and the number of crossings in the YG group and MG group were shortened , and the difference was not statistically significant. Compared with the OG group , there was a statistically significant difference in the exercise speed in the open field of the YG group (P < 0. 01) , there was no significant difference in the movement speed in the open field of the MG group , the number of entries into the central zone significantly increased in the MG group ( P < 0. 05 ) , and there was no significant difference in the number of entries in the YG group (P > 0. 05) . Compared with the OG group , the YG group had a statistically significant difference in the elevated cross maze (P < 0. 05) , the MG group had no statistically signif- icant difference in the elevated cross maze , and the number of closed arm entries in the YG group and MG group significantly increased (P < 0. 001 , P < 0. 01) . Compared with the YG group , the relative expression level of CaMKⅡ(pan) in the OG group was statistically significant ( P < 0. 05 ) , while the relative expression level of CaMKⅡ(pan) in the MG group was not statistically significant ( P > 0. 05) . Conclusion With the increase of age , the weight of C57BL/6J female mice gradually increased , the activity level and desire to explore gradually de- creased , the spatial memory ability also declined , and the anxiety level and anxiety-like behavior increased. This study helps to reveal the effect of age on the activity level and cognitive function of females , and provides a refer- ence for studying cognitive and memory decline in older females.

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective To investigate the role and underlying mechanism of activating transcription factor 3(ATF3)in suppressing lipopolysaccharide(LPS)-induced autophagy and inflammatory responses in macrophages.Methods Firstly,the gene expression omnibus(GEO)database was used to analyze ATF3 expression in peripheral blood mononuclear cells(PBMCs)from sepsis patients,and gene set enrichment analysis(GSEA)was performed to identify enriched signaling pathways.Secondly,RAW264.7 macrophages were divided into a blank control group and an LPS-stimulated group(100 ng/mL LPS).Western blotting and immunofluorescence assay were used to detect ATF3 protein expression and observe its subcellular localization,respectively.Lentiviral transduction was used to generate ATF3 knockdown and overexpression cell lines to evaluate their effects on cytokine release and bacterial clearance.Cleavage Under Targets and Tagmentation(CUT&Tag)sequencing was employed to identify downstream target genes transcriptionally regulated by ATF3.Furthermore,the impact of ATF3 knockdown or overexpression on autophagy-related gene 5(ATG5),autophagy-related gene 16-like 1(ATG16L1),and autophagy levels was evaluated.Results GEO analysis revealed that ATF3 expression was significantly elevated in PBMCs from sepsis patients(P<0.01),and GSEA showed significant enrichment of autophagy-related and inflammation-related pathways(P<0.01).In RAW264.7 cells,100 ng/mL LPS stimulation significantly increased ATF3 expression in the nucleus than the blank control group(P<0.01).ATF3 knockdown led to increased secretions of TNF-α and IL-6 and enhanced bacterial clearance of macrophages(P<0.01),whereas ATF3 overexpression significantly suppressed TNF-α and IL-6 releases,and remained bacterial clearance at a low level when compared with the conditions in the negative control(NC)group(P<0.01).CUT&Tag results demonstrated that ATF3 was enriched at the promoter regions of key autophagy genes Atg5 and Atg16l1.Compared with the NC group,ATF3 knockdown significantly up-regulated the protein levels of LC3-II/I,ATG5,and ATG16L1 while decreased p62 expression(P<0.01).Conversely,ATF3 overexpression inhibited the expression of LC3-II/I,ATG5,and ATG16L1(P<0.01),but had no significant effect on p62 level.Conclusion Sepsis induces elevated ATF3 expression in macrophages,and suppresses autophagic activity and down-regulates pro-inflammatory cytokines TNF-α and IL-6,which probably mediated by ATF3 regulating transcription of ATG5 and ATG16L1,suggesting ATF3 as a potential therapeutic target for autophagy-inflammation imbalance.

Objective To observe the clinical efficacy of Fangxiang Wentong Powder(composed of Salviae Miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Alpiniae Officinarum Rhizoma,Piper Longum,and Corydalis Rhizoma)acupoint application combined with Kuanxiong Aerosol in treating female patients with coronary slow flow(CSF)associated angina.Methods After sample size estimation,119 female inpatients diagnosed as CSF associated angina and differentiated as chest-qi obstruction with yang deficiency and cold accumulation syndrome of traditional Chinese medicine(TCM)were collected from the cardiovascular departments of the Third People's Hospital of Fujian University of Traditional Chinese Medicine,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine),Zhanjiang First Traditional Chinese Medicine Hospital,and Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2023 to March 2024.Using a table of random numbers,the patients were divided into a treatment group(84 cases)and a control group(35 cases)in a ratio of 5∶2.The control group was treated with Isosorbide Monomitrate Sustained-Release Capsules,while the treatment group was treated with application of Fangxiang Wentong Powder on acupoints of Danzhong(CV17),Gaohuang(BL43),and Xinshu(BL15),together with sublingual administration of Kuanxiong Aerosol.The treatment course for both groups covered 7 days.Before and after treatment,the changes in the simplified Seattle Angina Questionnaire(SAQ-7)scores,Chinese Quality of Life Questionnaire for Cardiovascular Patients(CQQC)scores,6-minute walking distance(6MWD),serum C-reactive protein(CRP)level,and white blood cell-to-mean platelet volume ratio(WMR)were observed.The TCM symptom efficacy was compared between the two groups,and adverse reactions were monitored.Results(1)There were 8 patients withdrew in the treatment group for failing in completing the questionnaires,and 2 patients withdrew in the control group for suffering headaches after taking nitrates.Eventually,109 patients completed the trial,including 76 in the treatment group and 33 in the control group.(2)After 7 days of treatment,the total effective rate for TCM symptom efficacy in the treatment group was 86.84%(66/76),and that in the control group was 72.73%(24/33).The intergroup comparison(tested by the chi-square test)showed that the TCM symptom efficacy in the treatment group was significantly superior to that in the control group.(3)After treatment,both groups showed improvements in the scores of activity limitation and angina frequency items of SAQ-7,and the treatment group also showed improvements in the scores of subjective satisfaction item of SAQ-7(P＜0.05).The treatment group's improvements in the scores of activity limitation,angina frequency,and subjective satisfaction items of SAQ-7 were significantly superior to those of the control group(P＜0.05).(4)After treatment,the CQQC scores in the treatment group was significantly improved(P＜0.05),while no significant improvement was observed in the control group(P＞0.05).The improvement of CQQC scores in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,both groups showed improvements in 6MWD(P＜0.05),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05).(6)After treatment,the serum levels of inflammatory indicators of CRP and WMR in the treatment group were significantly improved(P＜0.05),while no significant improvements were presented in the control group(P＞0.05).The improvements in serum CRP level and WMR value in the treatment group were significantly superior to those in the control group(P＜0.05).(7)No adverse reactions were found in the treatment group,indicating high safety.Conclusion Fangxiang Wentong Powder acupoint application combined with Kuanxiong Aerosol is more effective than Isosorbide Monomitrate Sustained-Release Capsules,improving exercise tolerance,decreasing inflammatory factor levels,and improving the quality of life to some extent during the treatment of female patients with CSF.

The triglyceride-glucose(TyG)index has emerged as a novel metabolic marker,and research on it in the intensive care unit(ICU)has gradually increased in recent years.The TyG index combines the levels of triacylglycerol(TG)and glucose,reflecting the body's insulin resistance(IR)and metabolic status,and its potential clinical applications have garnered widespread attention.Current studies indicate a significant association between the TyG index and the prognosis of ICU patients,metabolic syndrome,and various critical illnesses.However,despite some studies revealing the potential clinical value of the TyG index in critically ill patients,there is still a lack of systematic reviews to comprehensively assess the application status of this indicator in the ICU setting.This article aims to review the clinical applications of the TyG index in ICU patients and its relationship with prognosis,metabolic syndrome,and critical illnesses,emphasizing its importance in the assessment and management of critically ill patients,with the hope of providing references and insights for future related research.

Aluminum adjuvants are widely used in the field of vaccines due to their ability to induce efficient and long-lasting immune responses and good safety profile. With the development of immunology, the requirements for adjuvants have gradually increased, and traditional aluminum adjuvants can no longer meet all the needs of application. The development of novel aluminum adjuvants has become a hot research topic in order to achieve good immunity-enhancing effects and induce specific types and strengths of immune responses. This review briefly introduces the mechanism of action and safety of aluminum adjuvants, with focus on the research progress of novel aluminum adjuvants in recent years, mainly including nano-aluminum adjuvants and composite aluminum adjuvants (aluminum adjuvants compounded with immunity-stimulating molecules or delivery carriers), and a prospect of their future research direction, aiming to provide some reference for the further development and clinical application of aluminum adjuvants.