ObjectiveTo investigate how Xiaoyao Shukun decoction （XYSKD） regulates the formation and release of neutrophil extracellular traps （NETs） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， thereby reducing inflammation， inhibiting the excessive proliferation of fibroblasts in pelvic adhesion tissue， decreasing adhesion and fibrosis， and repairing the tissue damage in sequelae of pelvic inflammatory disease （SPID）. MethodsA total of 84 Wistar rats were randomly allocated into seven groups： blank， model， XYSKD （8 mg·kg^-1）， mTOR agonist （10 mg·kg^-1）， mTOR agonist + XYSKD （10 mg·kg^-1+8 mg·kg^-1）， mTOR inhibitor （2 mg·kg^-1）， and mTOR inhibitor + XYSKD （2 mg·kg^-1+8 mg·kg^-1）. The rat model of SPID was constructed by starvation， fatigue， and ascending Escherichia coli infection. After 14 days of drug intervention， the ultrastructure of fibroblasts in the pelvic adhesion tissue was observed by transmission electron microscopy. The general morphology of the uterus， fallopian tube， and ovary was observed by laparotomy. The levels of interleukin-1β （IL-1β）， interleukin-17 （IL-17）， and tumor necrosis factor-α （TNF-α） in the peritoneal flushing fluid were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of myeloperoxidase （MPO） and citrullinated histone 3 （H3） in the fallopian tube was detected by immunofluorescence. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the relative protein and mRNA levels， respectively， of neutrophil elastase （NE）， intercellular adhesion molecule-1 （CD54）， α-smooth muscle actin （α-SMA）， H3， PI3K， and Akt. ResultsCompared with the blank group， the model group presented a large number of collagen fibers in bundles， numerous cytoplasmic folds of fibroblasts， reduced or absent mitochondrial cristae， and disordered and expanded endoplasmic reticulum. By laparotomy， extensive pelvic congestion， connective tissue hyperplasia， thickening and hardening of the tubal end near the uterus， and tubal and ovarian adhesion or cyst were observed in the model group. In addition， the model group showed raised levels of IL-1β， IL-17， and TNF-α in the peritoneal flushing fluid （P<0.01）， increased average fluorescence intensities of MPO and H3 （P<0.01）， and up-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.01）. Compared with the model group， the mTOR agonist group showed increased fibroblasts and cytoplasmic folds， absence of mitochondrial cristae， endoplasmic reticulum dilation， and evident collagen fiber hyperplasia. Pelvic adhesions were observed to cause aggravated damage to the uterine， fallopian tube， and ovarian tissues. The levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid elevated （P<0.01） and the average fluorescence intensities of MPO and H3 enhanced （P<0.01） in the mTOR agonist group. In contrast， the XYSKD group and the mTOR inhibitor group showcased decreased fibroblasts and collagen fibers， alleviated mitochondrial crista loss and endoplasmic reticulum dilation， improved morphology and appearance of the uterine， fallopian tube， and ovarian tissues， lowered levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.05）. Compared with the mTOR agonist group， the mTOR agonist + XYSKD group showed alleviated pathological changes in the pelvic tissue， declined levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein levels of NE， H3， CD54， α-SMA， p-PI3K/PI3K， and p-Akt/Akt （P<0.01） and mRNA levels of NE， H3， CD54， α-SMA， PI3K， and Akt （P<0.01）. Compared with the mTOR inhibitor group， the mTOR inhibitor + XYSKD group demonstrated reduced pathological severity of the pelvic tissue， reduced levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE and CD54 （P<0.05）. ConclusionXYSKD can inhibit the excessive formation and release of NETs via PI3K/Akt/mTOR to ameliorate the inflammatory environment and reduce fibrosis and adhesion of the pelvic tissue， thereby playing a role in the treatment of SPID. It may exert the effects by lowering the levels of IL-1β， IL-17， and TNF-α and down-regulating the expression of NE， H3， CD54， α-SMA， PI3K， and Akt in the pelvic adhesion tissue.

Thyroid cancer is caused by multiple factors, including genetics, environment, metabolism, and the immune microenvironment, among which ionizing radiation exposure is an important risk factor for thyroid cancer. As one of the most sensitive target organs of ionizing radiation, the thyroid gland may have different risks of thyroid cancer caused by different types of ionizing radiation exposures, such as medical exposure, occupational exposure, and emergency exposure. The sensitivity of children and adolescents are higher than that of adults. The dose-response relationship still needs to be further explored. The molecular mechanism between ionizing radiation and the increased risk of thyroid cancer is complex, which may involve DNA damage and repair abnormalities, gene mutations, non-coding RNA regulation, DNA methylation, cell cycle regulation imbalance, and immune microenvironment changes. This article reviews the risk and molecular mechanisms associated with different types of ionizing radiation exposure in thyroid cancer, based on literature retrieved from CNKI and PubMed databases. It aims to provide a theoretical basis for the early monitoring, prevention, and intervention of thyroid cancer related to ionizing radiation exposure.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

Objective To review the characteristics of animal models of sequelae of pelvic inflammatory disease(SPID)to provide a reference for standardizing the modeling process and improving the modeling rate.Methods Literature relevant to animal models of SPID from the past 40 years was searched,and animal species,modeling method,modeling cycles,modeling substances,positive control drugs,and evaluation indexes were summarized and analyzed.Results A total of 243 study manuscripts were included,most of which induced the SPID model in rats via the phenol paste or microbial infection method.The modeling cycles were typically between 14 and 16 days,and the success of the models was mostly determined by pelvic tissue morphology observation and pathological HE staining.Few research reports have focused on the traditional Chinese medicine(TCM)disease combination model.Conclusions No consistent criteria have been established for SPID animal model modeling,and thus it is recommended that researchers evaluate changes to animal behavior,pelvic histomorphology,and pathology.TCM syndrome modeling lacks effective method and evaluation standards,which need further research and development.Finally,the selection and use of positive-control drugs need to be further explored and perfected.

Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

To improve the current situation of multiple preoperative visits and evaluations for elderly patients and other patients with complex conditions, in December 2022, Peking Union Medical College Hospital established preoperative multidisciplinary evaluation clinic (shorted as joint clinic). The joint clinic established a multidisciplinary team, clarified service targets, and developed standardized clinic workflows to provide patients with a " one-stop" preoperative assessment(physical fitness assessment, nutritional assessment, and frailty assessment, etc.), nutritional optimization intervention, and prerehabilitation education and guidance services. This practice strengthened preoperative risk management, improved preoperative assessment efficiency, and ensured the safety of patients during the perioperative period. As of September 2023, the joint clinic had received a total of 128 patients, of which 86 underwent surgery after preoperative evaluation and prehabilitation optimization. The obesity rate, smoking rate, and number of frailty cases of these patients had decreased from 13.96%, 11.63%, and 18 at the time of visit to 9.30%, 4.65%, and 14 on the day before surgery, respectively. They had recovered well after surgery. This practice had improved the preoperative status of patients and created conditions for high-risk patients to undergo surgery smoothly, so as to provide references for other hospitals to carry out multidisciplinary collaborative preoperative evaluation works.

Gallbladder cancer constitutes the most prevalent malignant tumor of the biliary tract. It exhibits clinical characteristics such as challenging diagnosis in early stages, aggressive invasiveness, and poor prognosis. Studies have discovered that the occurrence, development, and metastasis of malignant tumors are closely associated with the inflammatory response, and the level of systemic inflammation within the body can be reflected by peripheral blood inflammatory indicators. This review delineates the research progress on the correlation between peripheral blood inflammatory markers and the prognosis of gallbladder cancer, with the intention of providing references for the diagnosis, treatment, and prognosis evaluation of gallbladder cancer.

Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.