Technical variety of anastomotic techniques used in proximal gastrectomy with double-tract-reconstruction - a narrative review.

In the past 40 years, the incidence of esophagogastric junction cancer has been gradually increasing worldwide. Currently, surgical resection remains the main radical treatment for early gastric cancer. Due to the rise of functional preservation surgery, proximal gastrectomy has become an alternative to total gastrectomy for surgeons in Japan and South Korea. However, the methods of digestive tract reconstruction after proximal gastrectomy have not been fully unified. At present, the principal methods include esophagogastrostomy, double flap technique, jejunal interposition, and double tract reconstruction. Related studies have shown that double tract reconstruction has a good anti-reflux effect and improves postoperative nutritional prognosis, and it is expected to become a standard digestive tract reconstruction method after proximal gastrectomy. However, the optimal anastomoses mode in current double tract reconstruction is still controversial. This article aims to review the current status of double tract reconstruction and address the aforementioned issues.

Therapeutic potential of natural flavonoids in pulmonary arterial hypertension: A review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH. PURPOSE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates. METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included "pulmonary arterial hypertension", "pulmonary hypertension", "natural products", "natural flavonoids", "traditional chinese medicine", etc., and several combinations of these keywords. RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications. CONCLUSION: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.

Development of autoimmune thyroid disease after COVID-19 infection: case report.

Background: SARS-CoV-2 could trigger multiple immune responses, leading to several autoimmune diseases, including thyroid diseases. Many cases of thyroid diseases caused by COVID-19 infection have been reported. Here, we describe the disease development of patients with autoimmune thyroid disease after COVID-19 infection. Methods: The clinical characteristics, diagnosis and treatment of five different patients with autoimmune thyroid disease after COVID-19 infection were reported. Results: Female patients with primary autoimmune thyroid disease which have been stable for many years were reported. One month after COVID-19 infection, the disease has undergone different evolution. Case 1, a patient with history of long-term stable Hashimoto's thyroiditis, suddenly suffered from Graves disease after COVID-19 infection. Case 2, a patient with history of long-term stable Hashimoto's thyroiditis with thyroid nodules, suddenly suffered from Graves disease after infection. Case 3, a patient with history of long-term stable Graves disease, suddenly suffered from worsening after infection. The above three cases showed thyroid-stimulating antibodies were enhanced. Case 4, a patient with history of previous hypothyroidism had an increase in thyroid-related antibody (TPOAb and TRAb) activity after infection, followed by a marked worsening of hypothyroidism. Case 5, a patient with no history of thyroid disease suddenly developed controllable "thyrotoxicosis" after infection, suggesting the diagnosis of painless thyroiditis. Conclusion: The five case reports show a different development of the primary autoimmune thyroid disease after COVID-19 infection. The change in the trend of thyroid disease is closely related to the immune response induced by SARS-CoV-2 infection.

Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer.

N6-methyladenosine (m6A) is considered to be the most common and abundant epigenetics modification in messenger RNA (mRNA) and noncoding RNA. Abnormal modification of m6A is closely related to the occurrence, development, progression, and prognosis of cancer. m6A regulators have been identified as novel targets for anticancer drugs. Natural products, a rich source of traditional anticancer drugs, have been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progression and explore the prospects and structural modification mechanisms of natural products as potential drugs targeting m6A modification for cancer treatment.

Tumor mutational burden as a predictive biomarker for non-small cell lung cancer treated with immune checkpoint inhibitors of PD-1/PD-L1.

BACKGROUND: The significant clinical benefits of PD-1/PD-L1 immune checkpoint inhibitors (ICIP) in non-small cell lung cancer (NSCLC) have been widely recognized, emphasizing the urgent need for a reliable biomarker. In this study, we find the remarkable capacity of tumor mutational burden (TMB) to serve as an accessible and streamlined indicator. PATIENTS AND METHODS: We designed a retrospective cohort study, consisting of 600 NSCLC patients treated with ICIP. Association between TMB and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) has been explored. RESULTS: A strong positive correlation between TMB levels and OS, PFS rates, clinical benefit has been found when TMB > = 16(TMB > = 16 mutations/megabase (mut/Mb)). However, when TMB < 16, increasing TMB values did not exhibit a gradual stepwise increase in OS and PFS rates. The median months of OS in the TMB > = 16 and < 16 are 35.58, and 10.71 months respectively with average 12.39 months (p < 0.0001). The median months of PFS in the TMB > = 16 and < 16 are not-obtained, and 2.79 months respectively with an average of 3.32 months (p < 0.0001). The DCR in the TMB > = 16 and < 16 are 71.4% and 44.2% respectively with an average of 47.7% (p < 0.0001). The ORR in the TMB > = 16 and < 16 are 49.4% and 20.8% respectively with an average of 24.5% (p < 0.0001). CONCLUSION: The TMB > = 16 shows significantly associated with optimal ICIP treatment outcomes, including higher patient survival rates, delayed disease progression, and significant clinical benefits. These results present the potential of TMB as a promising biomarker candidate for NSCLC patients undergoing ICIP treatment.

Natural plant resource flavonoids as potential therapeutic drugs for pulmonary fibrosis.

Pulmonary fibrosis is an enduring and advancing pulmonary interstitial disease caused by multiple factors that ultimately lead to structural changes in normal lung tissue. Currently, pulmonary fibrosis is a global disease with a high degree of heterogeneity and mortality rate. Nitidine and pirfenidone have been approved for treating pulmonary fibrosis, and the quest for effective therapeutic drugs remains unabated. In recent years, the anti-pulmonary fibrosis properties of natural flavonoids have garnered heightened attention, although further research is needed. In this paper, the resources, structural characteristics, anti-pulmonary fibrosis properties and mechanisms of natural flavonoids were reviewed. We hope to provide potential opportunities for the application of flavonoids in the fight against pulmonary fibrosis.

Self-Assembled Monolayers of Bi-Functionalized Porphyrins: A Novel Class of Hole-Layer-Coordinating Perovskites and Indium Tin Oxide in Inverted Solar Cells.

Self-assembled monolayers (SAMs) offer the advantage of facile interfacial modification, leading to significant improvements in device performance. In this study, we report the design and synthesis of a new series of carboxylic acid-functionalized porphyrin derivatives, namely AC-1, AC-3, and AC-5, and present, for the first time, a strategy to exploit the large π-moiety of porphyrins as a backbone for interfacing the indium tin oxide (ITO) electrode and perovskite active layer in an inverted perovskite solar cell (PSC) configuration. The electron-rich nature of porphyrins facilitates hole transfer and the formation of SAMs, resulting in a dense surface that minimizes defects. Comprehensive spectroscopic and dynamic studies demonstrate that the double-anchored AC-3 and AC-5 enhance SAMs on ITO, passivate the perovskite layer, and function as conduits to facilitate hole transfer, thus significantly boosting the performance of PSCs. The champion inverted PSC employing AC-5 SAM achieves an impressive solar efficiency of 23.19 % with a high fill factor of 84.05 %. This work presents a novel molecular engineering strategy for functionalizing SAMs to tune the energy levels, molecular dipoles, packing orientations to achieve stable and efficient solar performance. Importantly, our comprehensive investigation has unraveled the associated mechanisms, offering valuable insights for future advancements in PSCs.

Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia.

PURPOSE: This study aimed to explore the impact of ABL1-tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients' prognosis from TKIs intake practices. Materials and Methods: Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. RESULTS: Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. CONCLUSION: TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

Gut microbiota: An emerging therapeutic approach of herbal medicine for prevention of colorectal cancer.

The gut dysbiosis has emerged as a prominent player in the pathogenesis and development of colorectal cancer (CRC), which in turn intensifies dysregulated gut microbiota composition and inflammation. Since most drugs are given orally, this dysbiosis directly and indirectly impinges the absorption and metabolism of drugs in the gastrointestinal tract, and subsequently affects the clinical outcome of patients with CRC. Herbal medicine, including the natural bioactive products, have been used traditionally for centuries and can be considered as novel medicinal sources for anticancer drug discovery. Due to their various structures and pharmacological effects, natural products have been found to improve microbiota composition, repair intestinal barrier and reduce inflammation in human and animal models of CRC. This review summarizes the chemo-preventive effects of extracts and/or compounds derived from natural herbs as the promising antineoplastic agents against CRC, and will provide innovative strategies to counteract dysregulated microbiota and improve the lives of CRC patients.

Polyacetylenes from Codonopsis lanceolata Root Induced Apoptosis of Human Lung Adenocarcinoma Cells and Improved Lung Dysbiosis.

Codonopsis lanceolata is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer and inflammation. However, the anticancer substances in C. lanceolata and their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from the water extracts of C. lanceolata polyacetylenes (CLP) and then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, and atractylenolide III. Treatment with CLP remarkably suppressed the cell proliferation, colony formation, migration, and invasion of A549 cells. Synergistic effects of lobetyolin and lobetyol were equivalent to the antiproliferative activities of CLP, while other compounds did not have any inhibition on the viabilities of A549 cells. CLP also reduced the expression of Ras, PI3K, p-AKT, Bcl-2, cyclin D1, and CDK4 but increased the expression of Bax, GSK-3ß, clv-caspase-3, and clv-caspase-9, which could be reversed by the PI3K activator 740YP. Furthermore, CLP retarded the growths of tumor and lung pathogenic bacteria in mice. It demonstrated that lobetyolin and lobetyol were the main antitumor compounds in C. lanceolata. CLP induced cell apoptosis of lung cancer cells via inactivation of the Ras/PI3K/AKT pathway and ameliorated lung dysbiosis, suggesting the therapeutic potentials for treating human lung cancer.

Analysis of peripherally inserted central catheter-related complications: a retrospective cohort study of 2,974 children with blood diseases in a single center of China.

BACKGROUND: Although the peripherally inserted central catheter (PICC) has been widely utilized, there is still a lack of large sample size-based relevant risk factor investigation for the children with blood diseases in a single center of China. METHODS: We performed a retrospective cohort study through including a total of 2,974 cases aged 0-18 years with blood diseases and PICC insertion. Success rates of different PICC operation techniques were compared. Targeting the common PICC-related complications, we performed the univariate and multivariate logistic regression analyses. Then, based on the screened risk factors, the prediction modeling analysis of binary logistic regression was conducted. RESULTS: The "B-ultrasound plus Seldinger technology" showed a higher success rate of PICC placement than the "non-assistive blind insertion". The catheter type was closely linked to the occurrence of catheter occlusion. The age, insertion site, and catheter type might be the risk factors of phlebitis, while the insertion site, operation season, and catheter type might be associated with catheter fracture. Furthermore, based on these risk factors, we established the nomogram prediction models of phlebitis, rash occurrence, and catheter fracture, respectively, which shows a good predictive ability and a moderate level of predictive accuracy. CONCLUSIONS: Our findings first shed new light on the preoperative estimation of the risk factors of PICCrelated complications for the children with blood diseases in China.

Correlation Between Raf/MEK/ERK Signaling Pathway and Clinicopathological Features and Prognosis for Patients With Breast Cancer Having Axillary Lymph Node Metastasis.

OBJECTIVE: This study aims to investigate the correlations between rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase signaling pathway and clinicopathological features and prognosis for patients with breast cancer having axillary lymph node metastasis. METHODS: A total of 118 breast cancer tissues with axillary lymph node metastasis (axillary lymph node metastasis group), 150 breast cancer tissues with non-axillary lymph node metastasis (non-axillary lymph node metastasis group), and 216 normal breast tissues (normal group) were enrolled in this study. The messenger RNA and protein expressions of rapidly accelerated fibrosarcoma, MEK, extracellular signal-regulated kinase, and their phosphorylated (p-) proteins were examined by reverse transcriptase quantitative polymerase chain reaction and immunohistochemistry, respectively. All patients received a 1-year follow-up, and the clinical follow-up data were collected. The multiple factors on the prognosis of patients with breast cancer having axillary lymph node metastasis were tested by Cox regression analysis. RESULTS: The messenger RNA expressions of rapidly accelerated fibrosarcoma, MEK, and extracellular signal-regulated kinase and positive rates of rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and p-extracellular signal-regulated kinase in the axillary lymph node metastasis group were higher than in the non-axillary lymph node metastasis and normal groups (all P < .05). The protein expressions of rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and p-extracellular signal-regulated kinase were associated with tumor size, clinical stage, and axillary lymph node metastasis number (all P < .05). Rapidly accelerated fibrosarcoma, MEK, and extracellular signal-regulated kinase expressions were significantly correlated with the prognosis of patients with breast cancer (all P < .05). Patients with BC having positive rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and phosphorylated ERK expressions had a higher survival rate than patients with BC having the negative ones (all P < .05). Rapidly accelerated fibrosarcoma and extracellular signal-regulated kinase protein expressions, clinical stage, pathological grade, and axillary lymph node metastasis number were independent prognostic factors in patients with breast cancer having axillary lymph node metastasis (all P < .05). CONCLUSION: Our study proved that rapidly accelerated fibrosarcoma/MEK/extracellular signal-regulated kinase signaling pathway is significantly correlated with the clinicopathological features and prognosis for patients with BC having axillary lymph node metastasis. Rapidly accelerated fibrosarcoma and extracellular signal-regulated kinase protein expressions are independent prognostic factors for patients with breast cancer having axillary lymph node metastasis.

Autophagic regulation of cell growth by altered expression of Beclin 1 in triple-negative breast cancer.

Beclin 1 is a promoter gene for autophagy as well as a key factor for regulating tumor cell growth and death. Allelic deletion of Beclin 1 has been observed in certain triple-negative breat cancer (TNBC) cells, and it might be associated with increased proliferation and invasion in TNBC cells. In this study we investigated the relationship between Beclin 1 expression and prognosis for TNBC patients, as well as the influence on cell growth by Beclin 1 overexpression in different cultural conditions. Beclin 1 expression in TNBC tissues was measured by immunohistochemical staining and correlated with clinicopathologic parameters for TNBC patients. The plasmid of pDS-RED-C1-Beclin 1 was transfected to BT-549 and MDA-MB-231 cells and autophagy, proliferation, apoptosis, cell cycle and Epithelial-mesenchymal transition (EMT) process were measured. Results indicated that high level of Beclin 1 expression was correlated with more lymph nodes and distant metastasis but unrelated to survival rates in 5 years for TNBC patients. In vitro, overexpression of Beclin 1 improved cellular autophagy in both BT-549 and MDA-MB-231 cells, inhibited cell proliferation at normal cultural condition and increased cell survival in starvation, hypoxia or with doxorubicin stimulation. Besides, Beclin 1 overexpression decreased cell apoptosis, induced cells to be in G0/G1 phase and promoted EMT process through Wnt/ß-catenin pathway in starvation. Thus, Beclin 1 overexpression plays a double role in BT-549 and MDA-MB-231 cell growth by elevating the capability of autophagy. These findings might be useful for searching a proper method for clinical therapy of TNBC from the aspect of autophagy in future.