Decoding the microbiota metabolome in hepatobiliary and pancreatic cancers: Pathways to precision diagnostics and targeted therapeutics.

We delve into the critical role of the gut microbiota and its metabolites in the pathogenesis and progression of hepatobiliary and pancreatic (HBP) cancers, illuminating an urgent need for breakthroughs in diagnostic and therapeutic strategies. Given the high mortality rates associated with HBP cancers, which are attributed to aggressive recurrence, metastasis, and poor responses to chemotherapy, exploring microbiome research presents a promising frontier. This research highlights how microbial metabolites, including secondary bile acids, short-chain fatty acids, and lipopolysaccharides, crucially influence cancer cell behaviors such as proliferation, apoptosis, and immune evasion, significantly contributing to the oncogenesis and progression of HBP cancers. By integrating the latest findings, we discuss the association of microbial alterations with HBP cancers, key metabolites, and their implications, and how metabolomics and microbiomics can enhance diagnostic precision. Furthermore, the paper explores strategies for targeted therapies through microbiome metabolomics, including the direct therapeutic effects of microbiome metabolites and potential synergistic effects on conventional therapies. We also recognize that the field of microbial metabolites for the diagnosis and treatment of tumors still has a lot of problems to be solved. The aim of this study is to pioneer microbial metabolite research and provide a reference for HBP cancer diagnosis, treatment, and prognosis.

Qingfei mixture mitigates immunosuppression of tumor microenvironment in non-small cell lung cancer by blocking stat1/Ido1-mediated tryptophan-kynurenine pathway.

Programmed death-1 (PD-1) acts as a T cell checkpoint and is important in controlling T cell exhaustion. Blocking the intercommunication across PD-1 and PD-L1 is promising for advanced lung cancer treatment. However, the response rate requires being strengthened. This study aimed to determine whether the combination treatment of Qingfei mixture (QFM) and PD-1 inhibitor could improve the sensitivity of monoclonal antibody by regulating STAT1/IDO1-mediated tryptophan (Trp)-kynurenine (Kyn) pathway. The in vivo imaging system, immunofluorescence, hematoxylin-eosin staining, TUNEL, flow cytometry, HPLC, and ELISA were used to estimate the anti-tumor effects in LLC-luc tumor-bearing C57BL/6 mice treated with QFM, PD-1 inhibitor, 2-NP (enhancer of STAT1 transcription), and FICZ (AhR agonist) alone or in combination. IFN-γ-mediated A549 and LLC cells were treated with QFM-containing serum and fludarabine (FLU, STAT1 inhibitor), and cell viability, apoptosis, and Kyn content were then evaluated using CCK-8 assays, flow cytometry, and HPLC assays, respectively. Additionally, the expressions of STAT1, IDO1, AhR, NFATc1, TRIP12, PD-1, and PD-L1 were measured in vivo and in vitro. We found QFM increased the anti-cancer actions of PD-1 inhibitors by increasing the CD8+IFNγ+ T cells infiltration and decreasing the ratio of Kyn/Trp. Besides, QFM-containing serum suppressed the proliferation and promoted apoptosis in A549 and LLC cells, meanwhile, FLU boosted the effects of QFM-containing serum. Moreover, the suppression of tumor growth in the combination therapy was attenuated in the mice receiving 2-NP or FICZ. The occurrence of the above results was accompanied by a decrease in STAT1, IDO1, AhR, PD-1, and PD-L1 expressions. Collectively, the findings suggested that QFM may increase the influences of PD-1 inhibitors at least partially by blocking the STAT1/IDO1-mediated tryptophan-kynurenine pathway in lung cancer.

Extraction, purification, structural characteristics, biological activities, and applications of polysaccharides from the genus Lilium: A review.

The genus Lilium (Lilium) has been widely used in East Asia for over 2000 years due to its rich nutritional and medicinal value, serving as both food and medicinal ingredient. Polysaccharides, as one of the most important bioactive components in Lilium, offer various health benefits. Recently, polysaccharides from Lilium plants have garnered significant attention from researchers due to their diverse biological properties including immunomodulatory, anti-oxidant, anti-diabetic, anti-tumor, anti-bacterial, anti-aging and anti-radiation effects. However, the limited comprehensive understanding of polysaccharides from Lilium plants has hindered their development and utilization. This review focuses on the extraction, purification, structural characteristics, biological activities, structure-activity relationships, applications, and relevant bibliometrics of polysaccharides from Lilium plants. Additionally, it delves into the potential development and future research directions. The aim of this article is to provide a comprehensive understanding of polysaccharides from Lilium plants and to serve as a basis for further research and development as therapeutic agents and multifunctional biomaterials.

Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Dryopteris crassirhizoma Nakai.: A review of its botany, traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: The Dryopteris crassirhizoma Nakai., a commonly used herb, is known as "Guan Zhong" in China, "Oshida" in Japan and "Gwanjung" in Korea. It has long been used for parasitic infestation, hemorrhages and epidemic influenza. AIM OF THE REVIEW: The present paper aims to provide an up-to-date review at the advancements of the investigations on the traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma. Besides, possible trends, therapeutic potentials, and perspectives for future research of this plant are also briefly discussed. MATERIALS AND METHODS: Relevant information on traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma was collected through published materials and electronic databases, including the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar, and China National Knowledge Infrastructure. 109 papers included in the article and we determined that no major information was missing after many checks. All authors participated in the review process for this article and all research paper are from authoritative published materials and electronic databases. RESULTS: 130 chemical components, among which phloroglucinols are the predominant groups, have been isolated and identified from D. crassirhizoma. D. crassirhizoma with its bioactive compounds is possessed of extensive biological activities, including anti-parasite, anti-microbial, anti-viral, anti-cancer, anti-inflammatory, anti-oxidant, anti-diabetic, bone protective, immunomodulatory, anti-platelet and anti-hyperuricemia activity. Besides, D. crassirhizoma has special toxicology and pharmacokinetics characterization. CONCLUSIONS: D. crassirhizoma is a traditional Chinese medicine having a long history of application. This review mainly summarized the different chemical components extract from D. crassirhizoma and various reported pharmacological effects. Besides, the toxicology and pharmacokinetics of D. crassirhizoma also be analysed in this review. However, the chemical components of D. crassirhizoma are understudied and require further research to expand its medicinal potential, and it is urgent to design a new extraction scheme, so that the active ingredients can be obtained at a lower cost.

Dichroa febrifuga Lour.: A review of its botany, traditional use, phytochemistry, pharmacological activities, toxicology, and progress in reducing toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Dichroa febrifuga Lour., a toxic but extensively used traditional Chinese medicine with a remarkable effect, is commonly called "Changshan" in China. It has been used to treat malaria and many other parasitic diseases. AIM OF THE REVIEW: The study aims to provide a current overview of the progress in the research on traditional use, phytochemistry, pharmacological activities, toxicology, and methods of toxicity reduction of D. febrifuga. Additionally, further research directions and development prospects for the plant were put forward. MATERIALS AND METHODS: The article uses "Dichroa febrifuga Lour." "D. febrifuga" as the keyword and all relevant information on D. febrifuga was collected from electronic searches (Elsevier, PubMed, ACS, CNKI, Google Scholar, and Baidu Scholar), doctoral and master's dissertations and classic books about Chinese herbs. RESULTS: 30 chemical compounds, including alkaloids, terpenoids, flavonoids and other kinds, were isolated and identified from D. febrifuga. Modern pharmacological studies have shown that these components have a variety of pharmacological activities, including anti-malarial activities, anti-inflammatory activities, anti-tumor activities, anti-parasitic activities and anti-oomycete activities. Meanwhile, alkaloids, as the material basis of its efficacy, are also the source of its toxicity. It can cause multiple organ damage, including liver, kidney and heart, and cause adverse reactions such as nausea and vomiting, abdominal pain and diarrhea. In the current study, the toxicity can be reduced by modifying the structure of the compound, processing and changing the dosage forms. CONCLUSIONS: There are few studies on the chemical constituents of D. febrifuga, so the components and their structure characterization contained in it can become the focus of future research. In view of the toxicity of D. febrifuga, there are many methods to reduce it, but the safety and rationality of these methods need further study.

(-)-Epicatechin protects against myocardial ischemia/reperfusion injury via autophagy-dependent ferroptosis.

AIM: (-)-Epicatechin (EPI) has physiological activities such as antioxidant, anti-inflammatory and immune enhancement. In this study, we elucidated the protective effects of EPI in myocardial ischemia/reperfusion injury (MI/RI) and its mechanisms. METHODS: An in vivo I/R model was constructed by performing left anterior descending coronary artery surgery on rats, and an in vitro I/R model was constructed by subjecting hypoxia/reperfusion treatment on H9C2 cells. The damage of cardiac tissues was detected by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (H&E) staining, and expressions of ferroptosis-related proteins were examined by Western blot. Changes in the number of autophagosomes, the levels of oxidative stress and Fe2+ were also examined. RESULTS: EPI reduced abnormal electrocardiogram waveform and infarct size caused by MI/RI in rats. The increasing trend of levels of reactive oxygen species (ROS) and Fe2+ was reversed by EPI, suggesting that EPI can reduce ferroptosis in vivo. Moreover, the levels of lipid ROS and LC3 in H9C2 cells were decreased with EPI treatment, and autophagy and ferroptosis were also alleviated in a dose-dependent manner in vitro. Co-cultivation of USP14 inhibitor IU1 and EPI further revealed that EPI regulates ferroptosis through the USP14-autophagy pathway. CONCLUSIONS: EPI can reduce the level of oxidative stress by promoting USP14 to reduce autophagy, thus inhibiting autophagy dependent ferroptosis and reducing oxidative stress, and has a protective effect on myocardial infarction/myocardial infarction.

Relapse of Low Back Pain After Internal Lumbar Fixation Was Diagnosed with SAPHO Syndrome: A Case Report.

Introduction: Early diagnosis of SAPHO syndrome is easily confused with other common spine-related diseases and infections. There is currently no consensus regarding the diagnosis of SAPHO syndrome, and specific treatments are empirical because of its rarity. Case Presentation: A 62-year-old woman was referred to our department with complaints of low back and lower extremity pain for 2 years, 1.5 years after lumbar spine surgery, and recurrent low back pain for 1 year. Laboratory test results revealed elevated hs-CRP levels and erythrocyte sedimentation rate. Combined with her surgical history and lumbar CT results, adjacent segment degeneration (ASD) was first considered. NSAIDs, analgesics, and supplemental therapies were also administered. However, the patient's symptoms were not significantly relieved. During re-examination, hyperkeratosis with active pustulosis was observed on the patient's palms. Osteitis of the left sacroiliac joint was revealed on imaging. Skeletal ECT revealed a typical "horn sign". The patient was diagnosed with SAPHO syndrome. Based on the original treatment, sulfasalazine enteric-coated tablets, adalimumab (a biological agent of TNF-α), pregabalin, and tramadol sustained-release tablets were administered. The patient reported that her pain was significantly relieved. He was discharged from the hospital and received adalimumab treatment (40 mg once per fortnight in the first 6 months and 40 mg once per month after month 6) in the outpatient clinic. The hyperkeratosis with active pustulosis on both palms fully recovered after 12 months of treatment. The patient was followed up 6 months after full recovery, and no recurrence was found in the symptoms of low back and lower extremity pain and palmar hyperkeratosis with active pustulosis. Conclusion: SAPHO syndrome should be suspected in patients present with osteoarticular and/or dermatological manifestations. Biological agents can be used to treat patients with refractory SAPHO syndrome.

Enhanced recovery nursing and mental health education on postoperative recovery and mental health of laparoscopic liver resection.

BACKGROUND: Patients undergoing laparoscopic resection of liver metastases of colorectal cancer are prone to negative emotions and decrease of digestive function. Early nursing and psychological intervention are necessary. AIM: To observe the effect of enhanced recovery nursing combined with mental health education on postoperative recovery and mental health of patients undergoing laparoscopic resection of liver metastases of colorectal cancer. METHODS: One hundred and twenty patients who underwent laparoscopic resection of liver metastases of colorectal cancer at our hospital between March 2021 and March 2023, were selected as participants. The patients admitted from March 1, 2021 to February 28, 2022 were set as the control group, and they were given routine nursing combined with mental health education intervention. While the patients admitted from March 1, 2022 to March 31, 2023 were set as the observation group, they were given accelerated rehabilitation surgical nursing combined with mental health education intervention. The differences in postoperative recovery-related indices, complications and pain degrees, and mental health-related scores were compared between groups. The T lymphocyte subset levels of the two groups were also compared. RESULTS: The postoperative exhaust, defecation, eating and drainage time of the observation group were shorter than those of the control group. The pain scores of the observation group were lower than those of the control group at 6, 12, 24, 48, and 72 h after surgery. The cumulative complication rate of the observation group was lower than that of the control group (P < 0.05). The CD4+/CD8+ in the observation group was higher than that in the control group 3 d after surgery (P < 0.05). After intervention, the self-rating depression scale, self-rating anxiety scale, avoidance dimension, and yielding dimension in Medical coping style (MCMQ) scores of the two groups were lower than those prior to intervention, and the scores in the observation group were lower than those in the control group (P < 0.05). The face dimension score in the MCMQ score was higher than that before intervention, and that of the observation group was higher than that of the control group (P < 0.05). After intervention, the total scores of the life function index scale (FLIC) and psychological well-being scores of cancer patients in the two groups, and the physical and social well-being scores in the observation group, were higher than those before intervention. The nursing satisfaction of the observation group was higher than that of the control group (P < 0.05). The physical, psychological, and social well-being, and the total FLIC scores of the observation group were higher than those in the control group after surgery (P < 0.05). CONCLUSION: Enhanced recovery nursing combined with mental health education can promote the recovery of gastrointestinal function, improve the mental health and quality of life of patients after laparoscopic resection of colorectal cancer liver metastases, and reduce the incidence of complications.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin.

BACKGROUND: Serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) is a promising biomarker for hepatocellular carcinoma (HCC) surveillance. AIM: To identify the contributing factors related to the abnormal elevation of PIVKA-II level and assess their potential influence on the performance of PIVKA-II in detecting HCC. METHODS: This study retrospectively enrolled in 784 chronic liver disease (CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve (AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-II for HCC, respectively. RESULTS: Elevated PIVKA-II levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase (ALP), and total bilirubin (TBIL) for CLD patients and aspartate aminotransferase (AST) and tumor size for HCC patients (all P < 0.05). Serum PIVKA-II were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal (ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST (all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-II was significantly higher compared to that in patients with TBIL > 1 × ULN (0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant (0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone. CONCLUSION: Serum PIVKA-II has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Surgical treatment of thoracic aortic pseudoaneurysm caused by Brucella melitensis.

Thoracic aortic pseudoaneurysm caused by Brucella melitensis is extremely rare with extremely few cases reported to date. Herein, we present the case of a 65 year-old man with a huge pseudoaneurysm of the proximal descending thoracic aorta, involving the left subclavian artery and distal arch. Surgery was performed to replace the proximal descending aorta with a self-made bovine pericardial duct and the left subclavian artery with a 10 mm artificial vessel under deep hypothermic circulatory arrest; the patient recovered uneventfully. However, continued follow-up is required for long-term results.

Advances in Microfluidics for Single Red Blood Cell Analysis.

The utilizations of microfluidic chips for single RBC (red blood cell) studies have attracted great interests in recent years to filter, trap, analyze, and release single erythrocytes for various applications. Researchers in this field have highlighted the vast potential in developing micro devices for industrial and academia usages, including lab-on-a-chip and organ-on-a-chip systems. This article critically reviews the current state-of-the-art and recent advances of microfluidics for single RBC analyses, including integrated sensors and microfluidic platforms for microscopic/tomographic/spectroscopic single RBC analyses, trapping arrays (including bifurcating channels), dielectrophoretic and agglutination/aggregation studies, as well as clinical implications covering cancer, sepsis, prenatal, and Sickle Cell diseases. Microfluidics based RBC microarrays, sorting/counting and trapping techniques (including acoustic, dielectrophoretic, hydrodynamic, magnetic, and optical techniques) are also reviewed. Lastly, organs on chips, multi-organ chips, and drug discovery involving single RBC are described. The limitations and drawbacks of each technology are addressed and future prospects are discussed.

Qingyihuaji Formula promotes apoptosis and autophagy through inhibition of MAPK/ERK and PI3K/Akt/mTOR signaling pathway on pancreatic cancer in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer.

BACKGROUND: Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation. METHODS: We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography-mass spectrometry (LC-MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC-MS-based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice. RESULTS: Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all-trans-retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL-8 and NF-κB pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all-trans-retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri-treated Lewis lung cancer (LLC). CONCLUSIONS: Overall, these results pointed out that P. copri-nervonic acid/all-trans-retinoic acid axis may contribute to the pathogenesis of NSCLC.

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome in Endometrioid Ovarian Cancer.

Emerging studies have revealed that N6-methyladenosine modification is involved in the development of various cancers. However, the m6A modification pattern of endometrioid ovarian cancer (EOC) has not been demonstrated. In the present study, high-throughput sequencing combined with methylated RNA immunoprecipitation (MeRIP-seq) and RNA sequencing were used to obtain the transcriptome-wide m6A modifications of endometrioid ovarian cancer for the first time. The roles of methyltransferase-like 3 (METTL3) in EOC cell line COV362 were explored. In total, 39,237 m6A-modified peaks related to 17,082 genes were identified in the EOC group, and 52,848 m6A peaks representing 19,349 genes were detected in endometriosis group. Functional enrichment analysis revealed that m6A enriched genes were associated with tight junctions, cell adhesion molecules, platinum drug resistance, adherens junction, and more. METTL3 knockdown in the COV362 cells significantly decreased cell proliferation, promoted cell apoptosis, and induced cell cycle arrest at the G0/G1 phase. Our study presented the transcriptome-wide m6A modifications of endometrioid ovarian cancer for the first time and revealed various differentially expressed genes with methylated m6A modifications. This study may provide new directions for in-depth research of the underlying molecular mechanisms and signaling pathways of EOC development and progression.

Microbial spectrum and drug resistance of pathogens cultured from gallbladder bile specimens of patients with cholelithiasis: A single-center retrospective study.

BACKGROUND: Bacterial infection is an important cause of cholelithiasis or gallstones and interferes with its treatment. There is no consensus on bile microbial culture profiles in previous studies, and identified microbial spectrum and drug resistance is helpful for targeted preventive and therapeutic drugs in the perioperative period. AIM: To analyze the bile microbial spectrum of patients with cholelithiasis and the drug susceptibility patterns in order to establish an empirical antibiotic treatment for cholelithiasis-associated infection. METHODS: A retrospective single-center study was conducted on patients diagnosed with cholelithiasis between May 2013 and December 2018. RESULTS: This study included 185 patients, of whom 163 (88.1%) were diagnosed with gallstones and 22 (11.9%) were diagnosed with gallstones and common bile duct stones (CBDSs). Bile culture in 38 cases (20.5%) was positive. The presence of CBDSs (OR = 5.4, 95%CI: 1.3-21.9, P = 0.03) and longer operation time (> 80 min) (OR = 4.3, 95%CI: 1.4-13.1, P = 0.01) were identified as independent risk factors for positive bile culture. Gram-negative bacteria were detected in 28 positive bile specimens, and Escherichia coli (E. coli) (19/28) and Klebsiella pneumoniae (5/28) were the most frequently identified species. Gram-positive bacteria were present in 10 specimens. The resistance rate to cephalosporin in E. coli was above 42% and varied across generations. All the isolated E. coli strains were sensitive to carbapenems, with the exception of one imipenem-resistant strain. K. pneumoniae showed a similar resistance spectrum to E. coli. Enterococcus spp. was largely sensitive to glycopeptides and penicillin, except for a few strains of E. faecium. CONCLUSION: The presence of common bile duct stones and longer operation time were identified as independent risk factors for positive bile culture in patients with cholelithiasis. The most commonly detected bacterium was E. coli. The combination of ß-lactam antibiotics and ß-lactamase inhibitors prescribed perioperatively appears to be effective against bile pathogens and is recommended. Additionally, regular monitoring of emerging resistance patterns is required in the future.

Conservative Treatment for Giant Lumbar Disc Herniation: Clinical Study in 409 Cases.

BACKGROUND: There have been several recent reports of lumbar disc herniation (LDH) resorption; however, large sample studies are lacking, and the mechanism(s) underlying this phenomenon is unclear. OBJECTIVES: To explore the feasibility and clinical outcomes of conservative treatment for giant LDH and to analyze the factors affecting the resorption of giant LDH. STUDY DESIGN: Observational study and original research. SETTING: This work was performed at a University Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine. METHODS: From January 2008 to December 2019, 409 patients with giant LDH who initially underwent nonsurgical treatment in our hospital were followed for 1-12 years to analyze the rate of surgical intervention, calculate the rate of resorption of protrusions, and the rate of excellent clinical outcomes. RESULTS: Eighty-nine of the 409 patients (21.76%) underwent surgery, while the remaining 320 patients (78.24%) constituted the non-surgical treatment group. The Japanese Orthopaedic Association (JOA) score in the 320 patients changed from 10.22 ± 3.84 points to 24.88 ± 5.69 points after treatment, and the rate of excellent outcomes was 84.06%. Among the 320 patients in the non-surgical treatment group, the protrusion percentage decreased from 70.08±30.95% to 31.67 ± 24.42%. One-hundred and eighty-nine patients (59.06%) had > 30% resorption of protrusions, and 81 patients (25.31%) had a significant resorption of protrusions of > 50%. Among 189 patients with resorption, the shortest resorption interval was 1 month, and the longest was 8 years, with 77 patients (40.74%) showing resorption within 6 months, 51 (26.98%) within 6-12 months, and 61 patients (32.28%) after 12 months. LIMITATION: The main limitations are that all patients were from the same site, and there was a lack of multicenter randomized controlled trials with which to compare data. CONCLUSIONS: Patients with giant LDH are less likely to develop progressive nerve injury and cauda equina syndrome if their clinical symptoms improve after treatment. As long as there is no progressive nerve injury or cauda equina syndrome, conservative treatment is preferred for giant disc herniation. Resorption is more likely with greater disc protrusions in the spinal canal. A ring enhancement bull's eye sign) around a protruding disc on enhanced magnetic resonance imaging is an important indicator of straightforward resorption.

A Narrative Review on Perioperative Pain Management Strategies in Enhanced Recovery Pathways-The Past, Present and Future.

Effective pain management is a key component in the continuum of perioperative care to ensure optimal outcomes for surgical patients. The overutilization of opioids in the past few decades for postoperative pain control has been a major contributor to the current opioid epidemic. Multimodal analgesia (MMA) and enhanced recovery after surgery (ERAS) pathways have been repeatedly shown to significantly improve postoperative outcomes such as pain, function and satisfaction. The current review aims to examine the history of perioperative MMA strategies in ERAS and provide an update with recent evidence. Furthermore, this review details recent advancements in personalized pain medicine. We speculate that the next important step for improving perioperative pain management could be through incorporating these personalized metrics, such as clinical pharmacogenomic testing and patient-reported outcome measurements, into ERAS program.

Application of Multigroup Technology in Non-Small-Cell Lung Cancer with Qi Stagnation and Blood Stasis Syndrome.

OBJECTIVE: To explore the basic characteristics of intestinal flora, metabolomics, and proteomics of non-small cell lung cancer (NSCLC) in patients with Qi stagnation and blood stasis syndrome. METHODS: Twelve NSCLC patients with Qi stagnation and blood stasis syndrome were selected for the QZXY group and 15 healthy volunteers were selected for the control group. Fecal samples from the two groups were collected to evaluate intestinal microecology using the 16s rDNA technique. Serum samples were collected to compare the differences in metabolomics and proteomics between the two groups using liquid chromatography-mass spectrometry (LC-MS). Another 34 NSCLC patients with other syndromes were selected for the nQZXY group and their serum samples were collected. Metabolomics differences between the QZXY and nQZXY groups were compared using LC-MS, and four metabolites with the most obvious differences were selected for receiver operation characteristic curve representation. Finally, multigroup results were analyzed using the WGCNA software. RESULTS: There were two significantly different types of bacteria (Aerococcaceae and Abiotrophia), 11 different proteins (six upregulated and five downregulated), and 38 different metabolites (nine upregulated, 29 downregulated) between the QZXY and control groups. There was a correlation between differential bacteria, proteins, and metabolites. The conjoint analysis found that the different substances were related to MAPK, PI3K/Akt, Ras signaling pathway, cancer pathways, and cytokine-cytokine receptor interaction. There were four significant differences in metabolites (Pseudouridine, phenlacetyl-C0A, L-glutamic, and phospho-anandamide) between the QZXY and nQZXY groups. CONCLUSIONS: NSCLC with Qi stagnation and blood stasis syndrome had specific intestinal flora and protein and metabolites, which were closely related to the occurrence and development of tumors.

Characteristics of organ cysts and their association with type A aortic dissection.

OBJECTIVE: We aimed to evaluate the incidence of organ cysts in patients with type A aortic dissection (TAAD) to assess the association between organ cysts and TAAD. METHODS: Between January 2018 and December 2018, all patients with TAAD undergoing aortic surgery at our center were enrolled into the study; patients undergoing isolated coronary artery bypass grafting at our center were selected as the control group. Baseline differences between the 2 groups were adjusted using propensity-score matching. The incidence of organ cysts was compared between the 2 groups in total and matched cohorts. RESULTS: We enrolled 290 patients with TAAD and 293 patients with coronary artery disease (control group). The incidence of all organ cysts, liver cysts, renal cysts, and other organ cysts, was significantly higher in the TAAD group than in the control group (50.0% vs. 35.5%, p<0.001; 24.5% vs. 10.2%, p<0.001; 33.4% vs. 24.9%, p=0.023; and 6.2% vs. 1.5%, p=0.005; respectively). Among the 191 propensity score-matched patient pairs, the incidence of organ cysts, liver cysts, renal cysts, and other organ cysts was also significantly higher in the TAAD group than in the control group (57.6% vs. 30.9%, p<0.001; 28.8% vs. 11.0%, p<0.001; 39.3% vs. 19.9%, p<0.001; and 8.4% vs. 1.0%, p=0.001; respectively). The incidence of cysts with single-organ and multiple-organ involvement was also significantly higher in the TAAD group than in the control group (34.0% vs. 20.4%, p=0.003; and 23.6% vs. 10.5%, p=0.001). CONCLUSION: Our results show a higher incidence of organ cysts in patients with TAAD which is indicative of a common pathogenetic pathway between organ cysts and aortic dissection.