ObjectiveTo explore the mechanism of action of Wendantang on ApoE^-/- hyperlipidemic mice using non-targeted metabolomics technology. MethodsMale C57BL/6J mice served as the normal control group （n=6）， and they were fed with regular chow， while male ApoE^-/- mice constituted the high-fat group （n=30）， and they were fed with a 60% high-fat diet. After 11 weeks of model establishment， the mice in the high-fat group were randomly divided into the model group， simvastatin group （3.3 mg·kg^-1）， and high-dose， medium-dose， and low-dose groups of Wendantang （26， 13， 6.5 g·kg^-1， respectively， in terms of crude drug amount）， with six mice in each group. The normal control group and the model group were gavaged with an equivalent volume of normal saline， and all groups continued to be fed their respective diets， receiving daily medication for 10 weeks with weekly body weight measurements. Serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， free fatty acids （NEFA）， blood glucose （GLU）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were detected in the mice. Pathological changes in liver tissue were observed using hematoxylin-eosin （HE） staining， and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS） was employed for metabolomic analysis of mouse liver tissue. ResultsCompared to the normal control group， the model group exhibited significantly increased body weight， blood lipid levels， and liver function （P<0.05， P<0.01）， with disordered liver tissue structure， swollen hepatocytes， and accompanying vacuolar fatty degeneration and inflammatory cell infiltration. Compared to the model group， the simvastatin group and Wendantang groups showed significantly reduced body weight， TG， NEFA， GLU， ALT， and AST levels （P<0.05， P<0.01）， with a significant increase in HDL-C levels （P<0.05， P<0.01）， demonstrating a dose-dependent effect. The lesion of the liver tissue section was obviously improved after administration， tending towards a normal liver tissue morphology. Analysis of liver metabolites revealed 86 differential metabolites between the normal control group and the model group， with the high-dose group of Wendantang able to regulate 56 of these metabolites. Twenty-two differential metabolites associated with hyperlipidemia were identified， mainly including chenodeoxycholic acid， hyocholic acid， taurine， glycocholic acid， dihydroceramide， hydroxy sphingomyelin C14∶1， arachidonic acid， and linoleic acid， enriching 22 metabolic pathways， with 4 being the most significant （P<0.05）， namely primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways. ConclusionWendantang can improve blood lipid levels and liver function in ApoE^-/- hyperlipidemic mice， which may be related to the regulation of primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways.

Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.

ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.

In recent years, the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection. Through research on the interaction mechanism between hosts and pathogenic bacteria, it has been found that the immune system is one of the key targets of host-acting antibacterial compounds. There is a communication system called the quorum sensing system in microorganisms, which mainly adjusts the structure of multi-microbial community and coordinates the group behavior. When the quorum sensing molecules secreted by microorganisms reach a threshold concentration, the quorum sensing system is activated and the overall gene expression of the microorganism is changed. In addition to regulating the density of microorganisms, quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts, entering the host immune system and playing a role in affecting the morphological structure of immune cells, secreting cytokines, and inducing apoptosis, leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone (AHL) molecules in the innate immune system has been extensively studied. The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains. Then, it acts through signaling pathways such as p38MAPK and JAK-STAT, further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis. Additionally, the human lactonase paraoxonase 2, which can degrade3-oxo-C12-HSL, has been found in macrophage. It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance. The mechanism of quorum sensing molecules in the adaptive immune system is less studied, the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells. For example, 3-oxo-C12-HSL induces apoptosis of Jurkat cells by inhibiting the expression of three mitochondrial electron transport chain proteins; it can also trigger mitochondrial dysfunction and induce mast cell apoptosis through Ca²⁺ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.

Transcrestal maxillary sinus floor elevation is an effective method to solve the problem of insufficient bone height in the posterior maxillary region.However,current methods,such as osteotome sinus floor elevation,cushioned grind-out technique,Smart Drill technique,etc.,require specialized surgical tool boxes.In this article,we introduce a new method of transcrestal maxillary sinus elevation that uses built-in reamers of various implant systems to scrap residu-al bone at the sinus floor and uses the implant to push the sinus membrane during implant placement.This technique is easy to operate and time saving and has a low rate of sinus membrane perforation.After a one-year follow-up observa-tion of 146 people and 175 implants,the endo-sinus bone gains were 5.00(4.70,5.30)mm and 2.10(1.40,2.70)mm in the group of 3 mm≤residual bone height(RBH)<5 mm and the group of 5 mm≤RBH<8 mm,respectively,which can meet the clinical requirements of implant stability.This technique is suitable in generalizing dental implantation.

Objective    To analyze the Ebstein anomaly's reoperative strategy and mid- to long-term results. Methods    We retrospectively reviewed the clinical data of 23 patients who diagnosed with Ebstein anomaly and underwent reoperation for tricuspid valve insufficiency between July 2002 and July 2017 in Fuwai Hospital. There were 9 (39.1%) males and 14 (60.9%) females, with a median age of 28.0 (19.0, 45.0) years. Results    Among the 23 patients, 8 (34.8%) underwent tricuspid valvuloplasty and 15 (65.2%) underwent tricuspid valve replacement. The rate of valvuloplasty was 16.7% before 2012, and 54.5% after 2012 (P=0.089) as Cone reconstruction procedure was used. In the valvuloplasty cohort, 3 (37.5%) patients were treated with Danielson or Carpentier technique, and 5 (62.5%) patients were treated with Cone reconstruction procedure. There was no operation-related death. Early complications occurred in 3 (37.5%) patients. The median follow-up was 6.9 years (range, 3.0-15.1 years), and no adverse cardiac events occurred. In the patients with valve replacement, 7 (46.7%) received mechanical prosthesis and 8 (53.3%) received bio-prosthesis. There was no operation-related death. And early complications were observed in 3 (20.0%) patients. The median follow-up was 6.5 years (range, 2.5-15.3 years). One (6.3%) patient died and 4 (26.7%) had long-term complications during the follow-up period. Conclusion    The mid- to long-term outcomes are convincing in patients who undergo the second operation due to recurrent tricuspid regurgitation of Ebstein anomaly. A low incidence of reoperation is observed. Cone reconstruction procedure provides possibilities of second tricuspid valvuloplasty, and this technique can reduce the rate of tricuspid valve replacement in the second operation. Tricuspid valve replacement is still an alternative method for the treatment of recurrent tricuspid regurgitation in patients with Ebstein anomaly. The bioprosthetic prosthesis may be a better choice than mechanical prosthesis.

Objective    To evaluate the clinical outcomes of  pulmonary valve replacement (PVR) in patients with tetralogy of Fallot (TOF) after re-PVR surgery. Methods    PubMed, EMbase, the Cochrane Controlled Trials Register databases, CNKI, CBM disc and VIP datebases were searched, and study eligibility and data abstraction were determined independently and in duplicate. Literature searches from database establishment to December 2018. The heterogeneity and data were analyzed by the software of Stata 11.0. Results    Of 4 831 studies identified, 26 studies met eligibility criteria, and invovled with a total of 3 613 patients. The combined 30-day mortality for PVR was 2.2% (95% CI 1.5%-3.1%) and follow-up mortality was 3.4% (95% CI 2.4%-4.9%), re-PVR rate was 6.8% (95% CI 5.1%-9.2%), and the rate of intervention was 11.4% (95% CI 8.0%-16.4%). Subgroup analysis showed that the patient's age range may be a heterogeneous source of mortality during the follow-up period, and there was no statistical heterogeneity for adult patients (P=0.63, I2=0%), with a lower incidence than those including adolescents patients. The type of valve was likely to be a source of retrospective PVR. There was no statistical heterogeneity in bioprosthetic valves and allograft lobes (P=0.24, I2=25%). And the incidence of re-PVR was lower than that of the mechanical valve patients. Heart function classification (NYHA) of patients with TOF after PVR was statistically improved (P<0.05). Electrocardiogram QRS change was not statistically differently (P>0.05). Postoperative MRI findings showed a decrease in RVEDV, an increase in RVEF, a decrease in RV/LV ratio, and a decrease in pulmonary valve (all P<0.05). Funnel map monitoring, Begg test and Egger's test both indicated that there was no publication bias. Conclusions    According to the results of the analysis, PVR after TOF surgery is a more mature surgery, the clinical effect was significant, with lower early and long-term mortality. The long-term mortality rate of adolescent patients undergoing PVR is higher than that of adult patients. Long-term outocme of re-PVR or re-intervention is still the main problem affecting the effect of the operation. Indications for surgery and choice of valve need further investigation.

Objective To analyze the multi-component,multi-target and multi-pathway mechanism of peony leaf in the treatment of cervical cancer based on network pharmacology. Methods The possible active components and targets in peony leaf were screened and predicted by pharmacological database and analysis platform of traditional Chinese medicine system,and the related targets of cervical cancer diseases were ob-tained by searching Therapeutic Target Database and others. The potential targets for the disease regulation were screened according to the active components of peony leaves entering blood,then the key target names and the pathways involved in the treatment of peony leaf were selected according to the network topological characteristic parameters. Then,the enrichment analysis was carried out by using ClueGO software plug-in. Results There were 194 target sites for 11 blood entry components in peony leaves. Finally,171 signal pathways were ob-tained,and 21 key pathways related to cervical cancer were obtained after the wide pathway was excluded,such as estrogen signaling pathway,neurotrophin signaling pathway and so on. Conclusion Peony leaves may play a vital role in the treatment of cervical cancer by acting on inflammatory,metabolic,immunological,endocrine and cell cycle related protein targets and pathways.

Objective: To explore the clinical effect of cervico-acromial fasciocutaneous flap based on the supraclavicular artery as a method for face and neck reconstruction. Methods: From Oct 1990 to June 2014, 17 patients, with the age range of 7 to 51 years, suffering from cicatricle contractures of neck or facial defect, were treated with cervico-acromial fascicutaneous flaps. 29 flaps were used in 12 patients bilaterally or multiply. The donor sites of 2 patients were closed by skin graft; while in the rest 15 patients, the donor sites were closed by expanded flaps. Results: All the 29 flaps were survived, with satisfactory color and texture. Hematoma occurred in 1 case after tissue expander implantation, but the flap was successfully expanded after evacuation of hematoma. The size of flaps ranged from 15 cm×7 cm to 35 cm×15 cm. 10 patients completed 6 months follow-up, and presented with satisfactory appearance and better functional results. Conclusions Cervico-acromial fascicutaneous flap based on the supraclavicular artery is an good choice for reconstruction of neck and facial defects.