Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

OBJECTIVE To identify the chemical components of Shenbai Jiedu Decoction(SBJDD),a traditional Chinese medi-cine(TCM)prescription clinically used for the treatment of colorectal adenoma(CRA),and explore the potential mechanism of SBJDD preventing and treating CRA carcinogenesis.METHODS An ultra-high performance liquid chromatography-time of flight-mass spectrometry(UPLC-Q-TOF-MS)method was established to detect the chemical components in the decoction of SBJDD and the plas-ma samples of rats after administration with SBJDD.Based on the network pharmacological method,SBJDD was screened for the poten-tial active ingredients at different stages of CRA carcinogenesis,and the mechanism of the anti-cancer effect of SBJDD was explored.In vitro experiments were also carried out to verify the mechanism of anti-colorectal cancer(CRC)action of SBJDD.RE-SULTS The detection data of UPLC-Q-TOF-MS showed that 152 components were found from SBJDD water extraction.41 chemical compounds were identified in plasma samples from rats administrated with SBJDD.Network pharmacology analysis indicated that during the CREI stage,the potential active ingredients in SBJDD,including epiberberine,and kushenol H,might affect target proteins such as PIK3CA,MAPK3 and PIK3CB.This,in turn,can influence signaling pathways like PI3K-AKT and Ras signaling pathways,and regulate biological processes like protein phosphorylation,and signal transduction.During the CRA stage,the potential active ingredi-ents from SBJDD,such as 3,7-dihydroxycoumarin,palmatine,and kushenol A,might affect target proteins such as AKT and EGFR.This can regulate the negative regulation of apoptotic process,and positive regulation of cell proliferation,and modify HIF-1,and Rap1 signaling pathways.During the progression of CRA carcinogenesis,potential active ingredients such as 3,7-dihydroxycouma-rin may interact with TP53,and impact the PI3K-AKT,and Thyroid hormone signaling pathways to regulate biological processes,in-cluding positive regulation of transcription from RNA polymerase Ⅱ promoter,and negative regulation of apoptotic process.In the CRC stage,core ingredients like p-coumaric acid may bind with proteins such as PRKCB.This binding may impact the signaling pathways that negatively affect EGFR tyrosine kinase inhibitor resistance,and PI3K-AKT signaling pathways.Additionally,it may regulate bio-logical processes,including negative regulation of apoptotic process,signal transduction,and protein phosphorylation.In vitro experi-ment results indicated that SBJDD inhibited the proliferation of HT29 cells and suppressed the expression of EGFR and PKC proteins.CONCLUSION The UPLC-Q-TOF-MS method is established to effectively separate the chemical constituents in SBJDD,which are mainly composed of alkaloids,organic acids and flavonoids components.Components from SBJDD dock with different targets during the carcinogenesis process of CRA and regulate cancer-related signaling pathways to exert therapeutic effects.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

ObjectiveTo compare and observe the effect of Reduning injection （mainly clearing heat）， Shenfu injection （mainly warming Yang） combined with gefitinib on the proliferation， apoptosis， stemness characteristics and metabolism of lung cancer cells. MethodDifferent non-small cell lung cancer （NSCLC） cell lines were selected and intervened with gefitinib （5， 10， 20 μmol·L^-1）， Reduning injection （0.6%， 0.9%）， Shenfu injection （0.6%， 0.9%）， gefitinib combined with Reduning injection， and gefitinib combined with Shenfu injection. Cell proliferation in each group was detected by cell counting kit-8 （CCK-8） assay， and cell apoptosis was detected by flow cytometry. The mRNA and protein expressions of lung cancer stem cell markers sex determining region Y-box 2 （Sox2） and aldehyde dehydrogenase family 1 member A1 （ALDH1A1） were determind by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The redox ratio of lung cancer cells was observed by femtosecond label-free imaging （FLI） and energy metabolism instrument was used to determine the glycolysis level in cells. ResultCompared with the blank group， Reduning injection reduced the survival rate of lung cancer cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， and up-regulated the redox ratio of cells （P<0.05）， while Shenfu injection exerted no remarkable effect on the above indexes. In addition， compared with gefitinib alone， Reduning injection combined with gefitinib inhibited the survival rate of lung cancer cells （P<0.05）， promoted the cell apoptosis （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， up-regulated the redox ratio of cells （P<0.05）， and lowered the proton efflux rate of glycolysis （P<0.05）， while Shenfu injection combined with gefitinib failed to affect these indexes of lung cancer cells significantly. ConclusionReduning injection may inhibit stemness characteristics of tumor cells by regulating their metabolism to enhance the proliferation-inhibiting and pro-apoptotic effects of gefitinib on lung cancer cells， while Shenfu injection had no significant enhancing effect on gefitinib. This indicates that epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） should be used in combination with heat-clearing Chinese medicines.

Hepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer, with high fatality rate. The pathogenesis of HCC is complex, and the specific occurrence and development mechanism is still in the exploratory stage. CircRNA is a special endogenous noncoding RNA and mainly participates in the regulation of gene expression at the transcriptional and posttranscriptional levels. By regulating gene transcription, it acts as a molecular sponge of miRNA, participates in protein translation, and interacts with RNA binding protein (RBP). CircRNA is involved in the occurrence and development of HCC. Its abnormal expression in HCC cells is related to the pathological characteristics of HCC tissue, regulates the expression of downstream target genes, miRNA and proteins, participates in the proliferation, migration, invasion and apoptosis of HCC cells, and regulates tumor microenvironment and signal pathways, suggesting that circRNA may be a potential novel biomarker and therapeutic target for the diagnosis and prognosis of HCC. This paper reviews the biological mechanism of circRNA, its role in HCC, and research progress in diagnosis and treatment.

Objective:To investigate the role of chest wall elastic resistance in determining the effects of positive end-expiratory pressure (PEEP) on central venous pressure (CVP) in patients with mechanical ventilation (MV).Methods:In this prospective study, according to the median of ratio of chest wall elastic resistance to respiratory system elastic resistance (Ers), patients were divided into high chest wall elastic resistance group (Ecw/Ers≥0.24) and low chest wall elastic resistance group [elastance of chest wall (Ecw)/Ers<0.24]. PEEP was set at 5, 10, 15 cmH 2O (1 cmH 2O=0.098 kPa) respectively. Clinical data including CVP, heart rate (HR), blood pressure (BP) and respiratory mechanics were recorded. Results:Seventy patients receiving MV were included from November 2017 to December 2018. Clinical characteristics including age, BP, HR, baseline PEEP, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) and comorbidities were comparable in two groups. However, patients with high Ecw/Ers ratio presented higher body mass index (BMI) than those with low Ecw/Ers ratio[ (25.4±3.2) kg/m 2 vs. (23.4±3.2) kg/m 2, P=0.011]. As PEEP increased from 5 cmH 2O to 10 cmH 2O, CVP in high Ecw/Ers group increased significantly compared with that in low Ecw/Ers group [1.75(1.00, 2.13) mmHg (1 mmHg=0.133kPa) vs. 1.50(0.50, 2.00)mmHg, P=0.038], which was the same as PEEP increased from 10 cmH 2O to 15 cmH 2O [2.00(1.50, 3.00)mmHg vs. 1.50(1.00, 2.00)mmHg, P=0.041] or PEEP increased from 5 cmH 2O to 15 cmH 2O [ 3.75(3.00,4.63)mmHg vs. 3.00(1.63, 4.00)mmHg, P=0.012]. When PEEP increased from 5 cmH 2O to 10 cmH 2O, 10 cmH 2O to 15 cmH 2O and 10 cmH 2O to 15 cmH 2O, there were significant correlations between Ecw/Ers and CVP elevation ( r=0.29, P=0.016; r=0.31, P=0.011; r=0.31, P=0.01 respectively). Conclusions:In patients receiving mechanical ventilation, elevation of PEEP leads to a synchronous change of CVP, which is corelated with patients′ chest wall elastic resistances.

Objective:To investigate the significance of changes of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in neoadjuvant therapy for rectal cancer.Methods:The data of 86 patients with rectal cancer who received neoadjuvant therapy from November 2013 to January 2015 in Shanxi Provincial Cancer Hospital were retrospectively analyzed, and the correlations of NLR and PLR changes with the patients' clinicopathological characteristics and therapeutic effects were also analyzed.Results:There were 43 cases of increased NLR and 43 cases of increased PLR after treatment. NLR and PLR changes before and after neoadjuvant therapy in patients with rectal cancer were not associated with age, gender, TNM stage, lymph node metastasis, number of cancer nodules, and tumor diameter (all P > 0.05). The increasing proportion of NLR and PLR after treatment in patients with the distance from the tumor to anus < 6 cm was higher than that in those with the distance≥6 cm [60.00% (30/50) vs. 36. 11% (13/36), χ2 = 4.778, P = 0.029; 64.00% (32/50) vs. 30.56% (11/36), χ2 = 9.364, P = 0.002]. The increasing proportion of NLR and PLR after treatment in patients with the body mass index (BMI) ≥28 kg/m 2 was higher than that in those with BMI < 28 kg/m 2 [81.82% (9/11) vs. 45.33% (34/75), χ2 = 5.108, P = 0.024; 90.91% (10/11) vs. 44.00% (33/75), χ2 = 8.444, P = 0.004]. The remission rate of patients in NLR reduction group after treatment was higher than that in NLR increase group [72.09% (31/43) vs. 51.16% (31/43), χ2 = 3.983, P = 0.046]. PLR changes were not associated with the therapeutic effects of neoadjuvant therapy before and after treatment ( P > 0.05). Conclusion:NLR changes are associated with therapeutic efficacy before and after neoadjuvant therapy for patients with rectal cancer.

Objective: To understand the association between body fat distribution and calcaneal bone mineral density (BMD) in children and adolescents aged 6-16 years in Beijing. Methods: Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method from November 2017 to January 2018. A total of 15 030 students in grade 1 to 4 of primary school, grade 1 of junior and senior middle school were enrolled after excluding subjects who were not able to participate into this study due to trauma or other uncomfortable physical conditions or with missing key values or with diabetes and kidney diseases. Questionnaire survey, body composition and calcaneus bone mineral density were conducted. The relation of fat mass percentage (FMP), trunk to total fat ratio (TrTFR), trunk to limb fat ratio (TrLFR), limb to total fat ratio (LTFR) and viscera to total fat ratio (VTFR) with calcaneus BMD were assessed using the multivariate linear regression models after adjusting for possible confounding effects. The central fat distribution types were divided into 4 groups including type 1: both trunk fat and visceral fat greater than the sex-and age-specific internal P₇₅; type 2: barely trunk fat greater than P₇₅; type 3: barely visceral fat greater than P₇₅; type 4: both trunk fat and visceral fat greater than P₇₅. The central fat distribution types were included into the model in the form of dummy variables to analyze its relationship with calcaneal BMD. The sex-and age-specific z-scores of fat distribution indicators and BMD were calculated. Results: A total of 15 030 participants aged (11.4±3.3) years (50.2% boys) were involved in the analysis. In both genders, after adjusting for age, height, lean mass index, smoking, drinking, physical activity, milk intake, vitamin D and calcium supplementation, FMP, TrTFR, TrLFR and VTFR were negatively correlated with calcaneal BMD (all P value<0.05), while LTFR was positively associated with calcaneal BMD (all P values<0.05). Compared to the central fat distribution type 1, the regression coefficients (95% CI) of type 2, 3 and 4 were -0.253 (-0.418, -0.087), -0.385 (-0.567, -0.204) and -0.428 (-0.487, -0.369) in boys, respectively; the regression coefficients (95% CI) of type 3 and 4 were -0.158 (-0.301, -0.015) and -0.226 (-0.290, -0.163), respectively. Conclusion Body fat distribution and central fat distribution in children and adolescents were correlated with calcaneus bone mineral density.

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.