Simultaneous integrated boost intensity-modulated radiotherapy post breast-conserving surgery: clinical efficacy, adverse effects, and cosmetic outcomes in breast cancer patients.

BACKGROUND: Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients. METHODS: We conducted a retrospective analysis of 308 patients with stage 0-III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes. RESULTS: The median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1-2 skin reactions (91.6%). The most common late toxicity was grade 0-1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1-2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes. CONCLUSIONS: SIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery.

Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD. Methods: Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected. Results: YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment. Conclusions: YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

Six versus four or five cycles of first-line etoposide and platinum-based chemotherapy combined with thoracic radiotherapy in patients with limited-stage small-cell lung cancer: A propensity score-matched analysis of a prospective randomized trial.

OBJECTIVES: The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. MATERIALS AND METHODS: In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. CONCLUSION: Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.

Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study.

BACKGROUND: For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC. METHODS: This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325-0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236-0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280-0.858], P = 0.011; HR 0.454 [95%CI 0.246-0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis. CONCLUSIONS: Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is recorded in Puji Benshi Fang for the treatment of intestinal carbuncle. It has been incorporated into the prescriptions for the treatment of intestinal diseases and achieved remarkable results in modern medicine. However, the mechanism of F.S in the treatment of colorectal cancer remains unclear and requires further study. AIM OF THE STUDY: To investigate F.S in treating CRC and clarify the underlying mechanism. MATERIALS AND METHODS: This study was based on Dextran Sulfate Sodium Salt (DSS) combined with Azoxymethane (AOM) induced CRC mouse model to clarify the pharmacological effects of F.S. The serum metabolomics was used to study the mechanism of action, and the chemical composition of F.S was found by UPLC-Q-TOF-MS. The rationality of serm metabolomics results was verified through the clinical target database of network pharmacology, and the upstream and downstream targets of related pathways were found. The mechanism pathway was verified by Western blot to clarify its mechanism of action. RESULTS: In vivo pharmacological experiments showed that F.S inhibited tumor growth and improved hematochezia. The vital signs of mice in the high-dose F.S group approached to those in the control group. A total of 43 differential metabolites were found to be significantly changed by serum metabolomics. F.S could modulate and recover most of the differential metabolites, which proved to be closely related to the KRAS/MEK-ERK signaling pathway. A total of 46 compounds in F.S were identified, and the rationality of serm metabolic pathway was verified by network pharmacology. Western blot results also verified that the expression of KRAS, E2F1, p-MEK and p-ERK were significantly decreased after F.S treatment. CONCLUSION: Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

Role of dynamic contrast-enhanced MRI in predicting severe acute radiation-induced rectal injury in patients with rectal cancer.

OBJECTIVES: To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters in predicting severe acute radiation-induced rectal injury (RRI) in rectal cancer. METHODS: This retrospective study enrolled 49 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and rectal MRI including a DCE-MRI sequence from November 2014 to March 2021. Two radiologists independently measured DCE-MRI quantitative parameters, including the forward volume transfer constant (Ktrans), rate constant (kep), fractional extravascular extracellular space volume (ve), and the thickness of the rectal wall farthest away from the tumor. These parameters were compared between mild and severe acute RRI groups based on histopathological assessment. Receiver operating characteristic curve analysis was performed to analyze statistically significant parameters. RESULTS: Forty-nine patients (mean age, 54 years ± 12 [standard deviation]; 37 men) were enrolled, including 25 patients with severe acute RRI. Ktrans was lower in severe acute RRI group than mild acute RRI group (0.032 min-1 vs 0.054 min-1; p = 0.008), but difference of other parameters (kep, ve and rectal wall thickness) was not significant between these two groups (all p > 0.05). The area under the receiver operating characteristic curve of Ktrans was 0.72 (95% confidence interval: 0.57, 0.84). With a Ktrans cutoff value of 0.047 min-1, the sensitivity and specificity for severe acute RRI prediction were 80% and 54%, respectively. CONCLUSION: Ktrans demonstrated moderate diagnostic performance in predicting severe acute RRI. CLINICAL RELEVANCE STATEMENT: Dynamic contrast-enhanced MRI can provide non-invasive and objective evidence for perioperative management and treatment strategies in rectal cancer patients with acute radiation-induced rectal injury. KEY POINTS: • To our knowledge, this study is the first to evaluate the predictive value of contrast-enhanced MRI (DCE-MRI) quantitative parameters for severe acute radiation-induced rectal injury (RRI) in patients with rectal cancer. • Forward volume transfer constant (Ktrans), derived from DCE-MRI, exhibited moderate diagnostic performance (AUC = 0.72) in predicting severe acute RRI of rectal cancer, with a sensitivity of 80% and specificity of 54%. • DCE-MRI is a promising imaging marker for distinguishing the severity of acute RRI in patients with rectal cancer.

A prognostic model based on Scissor+ cancer associated fibroblasts identified from bulk and single cell RNA sequencing data in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most lethal diseases in the world, which often recur after multimodality treatment approaches, leading to a poor prognosis. Fibroblasts, a heterogeneous component of the tumor microenvironment, can modulate numerous aspects of tumor biology and have been increasingly acknowledged in dictating the clinical outcome of patients with HNSCC. However, the subpopulation of fibroblasts that are related to the prognosis of HNSCC has not yet been fully explored. To do so, we combined a single-cell RNA sequencing (scRNA-seq) dataset and bulk RNA-sequencing dataset with clinical information, identifying the fibroblast population that are related to poor prognosis of HNSCC. We found these specific population of fibroblasts are less differentiated. In addition, to identify the prognostic signatures of HNSCC, bioinformatics analysis included least absolute shrinkage and selection operator (LASSO) analyses and univariate cox and were performed. We selected 12 prognosis-related genes for constructing a risk model using The Cancer Genome Atlas (TCGA). The AUC values and calibration plots of this model indicated good prognostic prediction efficacy. This model also was validated in two Gene Expression Omnibus (GEO) datasets. In conclusion, we constructed an optimal model that was derived from single cell RNA-seq and bulk RNA-seq to predict the survival probability of HNSCC patients. Among this model, AKR1C3 higher expression in cancer associated fibroblasts (CAFs) of HNSCC has been confirmed by preliminary experiments.

Effect of Oroxylum indicum on hepatocellular carcinoma via the P53 and VEGF pathways based on microfluidic chips.

BACKGROUND: Hepatocellular carcinoma (HCC), abbreviated as liver cancer, is one of the most common cancers in clinics. HCC has a wider spread and higher incidence due to its high malignancy and metastasis. In HCC, effective strategies to block cancer cell migration, invasion, and neovascularization need to be further studied. Consumption of flavonoid-rich Oroxylum indicum (OI) has been associated with multiple beneficial effects, including anti-inflammatory and anticancer properties, but the potential effects on HCC have not been thoroughly investigated. OBJECTIVE: In this study, we aimed to reveal the effect of OI on HCC and its potential mechanism through microfluidic technology. METHODS: We designed microfluidic chips for cell migration, invasion, and neovascularization to evaluate the effect of OI on HepG2 cells. To further explore the mechanism of its anti-liver cancer action, the relevant signaling pathways were studied by microfluidic chips, RT‒qPCR and immunofluorescence techniques. Compared to the control group, cell migration, invasion, and angiogenesis were significantly reduced in each administration group. According to the P53 and VEGF pathways predicted by network pharmacology, RT‒qPCR and immunofluorescence staining experiments were conducted. RESULTS: The results showed that OI upregulated the expression of Bax, P53 and Caspase-3 and downregulated the expression of Bcl-2 and MDM2. It has been speculated that OI may directly or indirectly induce apoptosis of HepG2 cells by regulating apoptosis-related genes. OI blocks the VEGF signaling pathway by downregulating the expression levels of VEGF, HIF-1α and EGFR and inhibits the migration and invasion of HepG2 cells and the formation of new blood vessels. CONCLUSION: Our findings suggest that OI may inhibit the migration, invasion, and neovascularization of HepG2 cells, and its regulatory mechanism may be related to the regulation of the P53 and VEGF pathways.

Efficacy analysis of axillary approach in the treatment of Ideberg type I and II scapular glenoid fractures: Case series.

RATIONALE: To investigate the clinical efficacy of the axillary approach in the surgical treatment of Ideberg type I and II scapular glenoid fractures. PATIENT CONCERNS AND DIAGNOSIS: Retrospective analysis of 13 cases of scapular glenoid fracture treated in the affiliated Hospital of Jining Medical College, Jiaxiang County People hospital, Zoucheng City people Hospital, Yanzhou District People Hospital, and Juancheng County people Hospital from December 2020 to January 2022. Eight males (including 1 bilateral) and 5 females, with an average age of 57.5 years (range from 33 to 75 years). According to Ideberg classification, there were 10 cases of type I a, 1 case of type I a combined with type I b, and 2 cases of type II. All patients were treated with axillary approach surgery and 7 patients with combined anterior shoulder dislocation were treated by first-stage manipulation and second-stage reoperation. Seven patients were fixed with a wire anchor, 3 patients with type I a were fixed with a "T" plate, and 5 patients were complicated with rotator cuff tear and were repaired with a wire anchor. At the last follow-up, the Constant-Murley shoulder function score, visual analog score, DASH score, and Hawkins grade were used to evaluate shoulder function, pain, and stability after treatment. INTERVENTION: The intervention was to treat patients with Ideberg type I and II scaphoid fractures using an axillary approach. OUTCOMES: All 13 patients in this group were followed up thoroughly, and the follow-up time was 12 to 25 months, with an average of 18.6 months. The operation time was 65 to 135 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 to 120 mL, averaging 55.6 mL. The duration of hospitalization ranged from 7 to 22 days, with an average of 9.6 days. The surgical incisions of all patients were grade-A healing. Bone healing of glenoid fractures was observed 3 months after the operation. LESSONS: The axillary approach for Ideberg type I and II scapular glenoid fractures is a feasible surgical approach with complete access through the muscle gap, minimal surgical trauma, mild postoperative pain, and satisfactory clinical results.

The role of MRI after neochemoradiotherapy in predicting pathological tumor regression grade and clinical outcome in patients with locally advanced rectal adenocarcinoma.

Objective: To evaluate the predictive value of tumor regression grade assessed by MRI (mr-TRG) after neoadjuvant chemoradiotherapy (neo-CRT) for postoperative pathological TRG (pTRG) and prognosis in patients with locally advanced rectal adenocarcinoma (LARC). Materials and methods: This was a retrospective study from a single center experience. The patients who were diagnosed with LARC and received neo-CRT in our department between January 2016 and July 2021 were enrolled. The agreement between mrTRG and pTRG was assessed with the weighted κ test. Overall survival (OS), progress-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier analysis and log-rank test. Results: From January 2016 to July 2021, 121 LARC patients received neo-CRT in our department. Among them, 54 patients had complete clinical data, including MRI of pre- and post-neo-CRT, postoperative tumor samples, and follow-up. The median follow-up time was 34.6 months (range: 4.4-70.6 months). The estimated 3-year OS, PFS, LRFS and DMFS were 78.5%, 70.7%, 89.0%, and 75.2%, respectively. The median time from the completion of neo-CRT to preoperative MRI and surgery was 7.1 weeks and 9.7 weeks, respectively. Out of 54 patients, 5 patients achieved mrTRG1 (9.3%), 37 achieved mrTRG2 (68.5%), 8 achieved mrTRG3 (14.8%), 4 achieved mrTRG4 (7.4%), and no patient achieved mrTRG5 after neo-CRT. Regarding pTRG, 12 patients achieved pTRG0 (22.2%), 10 achieved pTRG1 (18.5%), 26 achieved pTRG2 (48.1%), and 6 achieved pTRG3 (11.1%). The agreement between three-tier mrTRG (mrTRG1 vs. mrTRG2-3 vs. mrTRG4-5) and pTRG (pTRG0 vs. pTRG1-2 vs. pTRG3) was fair (weighted kappa=0.287). In a dichotomous classification, the agreement between mrTRG(mrTRG1 vs. mrTRG2-5)and pTRG(pTRG0 vs. pTRG1-3) also resulted in fair agreement (weighted kappa=0.391). The sensitivity, specificity, positive, and negative predictive values of favorable mrTRG (mrTRG 1-2) for pathological complete response (PCR) were 75.0%, 21.4%, 21.4%, and 75.0%, respectively. In univariate analysis, favorable mrTRG (mrTRG1-2) and downstaging N were significantly associated with better OS, while favorable mrTRG (mrTRG1-2), downstaging T, and downstaging N were significantly associated with superior PFS (p<0.05). In multivariate analysis, downstaging N was an independent prognostic factor for OS. Meanwhile, downstaging T and downstaging N remained independent prognostic factors for PFS. Conclusions: Although the consistency between mrTRG and pTRG is only fair, favorable mrTRG after neo-CRT may be used as a potential prognostic factor for LARC patients.

Possible mechanisms associated with immune escape and apoptosis on anti-hepatocellular carcinoma effect of Mu Ji Fang granules.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common digestive system cancers with high mortality rates worldwide. The main ingredients in Mu Ji Fang Granules (MJF) are alkaloids, flavonoids, and polysaccharides. MJF has been used in the clinical treatment of hepatitis, cirrhosis and HCC for more than 30 years. Few previous studies have focused on the mechanism of MJF on tumor immu-nology in the treatment of HCC. AIM: To explore the mechanism of action of MJF on tumor immunology in the treatment of HCC. METHODS: The absorbable ingredients of MJF were identified using Molecule Network related to High Performance Liquid Chromatography-Electron Spray Ionization-Time of Flight- Mass Spectrometry, and hub potential anti-HCC targets were screened using network pharmacology and pathway enrichment analysis. Forty male mice were randomly divided into the Blank, Model, and MJF groups (1.8, 5.4, and 10.8 g/kg/d) following 7 d of oral administration. Average body weight gain, spleen and thymus indices were calculated, tumor tissues were stained with hematoxylin and eosin, and Interferon gamma (IFN-γ), Tumor necrosis factor α (TNF-α), Interleukin-2, aspartate aminotransferase, alanine aminotransferase, alpha-fetoprotein (AFP), Fas, and FasL were measured by Enzyme-linked Immunosorbent Assay. Relevant mRNA expression of Bax and Bcl2 was evaluated by Real Time Quantitative PCR (RT-qPCR) and protein expression of Transforming growth factor ß1 (TGF-ß1) and Mothers against decapentaplegic homolog (SMAD) 4 was assessed by Western blotting. The HepG2 cell line was treated with 10 mg/mL, 20 mg/mL, 30 mg/mL, 40 mg/mL of MJF, and another 3 groups were treated with TGF-ß1 inhibitor (LY364947) and different doses of MJF. Relevant mRNA expression of TNF-α, IFN-γ, Bax and Bcl2 was evaluated by RT-qPCR and protein expression of TGF-ß1, SMAD2, p-SMAD2, SMAD4, and SMAD7 was assessed by Western blotting. RESULTS: It was shown that MJF improved body weight gain and tumor inhibition rate in H22 tumor-bearing mice, protected immune organs and liver function, reduced the HCC indicator AFP, affected immunity and apoptosis, and up-regulated the TGF-ß1/SMAD signaling pathway, by increasing the relative expression of TGF-ß1, SMAD2, p-SMAD2 and SMAD4 and decreasing SMAD7, reducing immune factors TNF-α and IFN-γ, decreasing apoptosis cytokines Fas, FasL and Bcl2/Bax, and inhibiting the effect of LY364947 in HepG2 cells. CONCLUSION: MJF inhibits HCC by activating the TGF-ß1/SMAD signaling pathway, and affecting immune and apoptotic cytokines, which may be due to MJF adjusting immune escape and apoptosis.

[Mechanism of famous classical formula Huaihua Powder in treatment of ulcerative colitis based on metabonomics].

Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1ß in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.

A study of the prognosis of patients with limited-stage small cell lung cancer who did or did not receive prophylactic cranial irradiation after effective chemoradiotherapy.

Objective: To investigate the prognosis of patients with LS-SCLC who responded to chest chemoradiotherapy but did not receive PCI. Methods: A retrospective analysis was conducted on LS-SCLC patients who had achieved complete remission (CR) or partial remission (PR) after definitive chemoradiotherapy but did not receive PCI. The survival rates were calculated using Kaplan-Meier method. The prognosis was analyzed using Cox proportional hazard regression model. The main endpoint was OS. Results: Of the 500 patients with LS-SCLC admitted between June 2002 and January 2018, 327 achieved CR or PR after definitive chest chemoradiotherapy, 103 did not receive PCI, and 63 of them developed brain metastases (BM). The 1-year and 3-year OS rates in PCI group were 87.5% and 42.3% respectively, versus 70.4% and 20.9% for non-PCI group(P=0.002). The median survival time after BM was 8.7 months (range: 0.3-48.7), and 3-year OS rate was 15.0%, the median survival time of patients without BM was 20.1 months (range: 2.9-79.4), and 3-year OS was 33.4% (P=0.014). Patients with BM were subsequently treated with palliative therapy. Multivariate analysis showed that compared with no treatment, brain radiotherapy alone (HR: 0.131, 95%CI: 0.035-0.491, P=0.003) and radiotherapy combined with chemotherapy (HR: 0.039, 95%CI: 0.008-0.194, P<0.001) significantly reduced the risk of death. Multiple BM (HR: 2.391, 95%CI: 1.082-5.285, P=0.031) was an independent adverse prognostic factor for OS. Conclusion: LS-SCLC patients who achieved good response after chest chemoradiotherapy without receiving PCI were prone to develop BM and have a poor prognosis. Multiple BM was an independent adverse prognostic factor. PCI remains the standard of care for LS-SCLC patients.

Patrinia villosa treat colorectal cancer by activating PI3K/Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: At present, the colorectal cancer (CRC) is a malignant tumor of the colon and rectum that is often found at the junction of the two, and it will invade many visceral organs and organizations, causing very serious damage to the body of the patient. Patrinia villosa Juss. (P.V), is a well-known traditional chinese medicine (TCM), and is recorded in the Compendium of Materia Medica as a necessary article for the treatment of intestinal carbuncle. It has been incorporated into traditional cancer treatment prescriptions in modern medicine. While the mechanism of action of P.V in the treatment of CRC remains unclear. AIM OF THE STUDY: To investigate P.V in treating CRC and clarify the underlying mechanism. MATERIALS AND METHODS: This study was based on Azoxymethane (AOM) combined with the Dextran Sulfate Sodium Salt (DSS)-induced CRC mouse model to clarify the pharmacological effects of P.V. The mechanism of action was found by metabolites and metabolomics. The rationality of metabolomics results was verified through the clinical target database of network pharmacology, and find the upstream and downstream target information of relevant action pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using quantitative PCR (q-PCR) and Western blot. RESULTS: The number and the diameter of tumors were decreased when mice were treated with P.V. P.V group section results showed newly generated cells which improved the degree of colon cell injury. Pathological indicators presented a trend of recovery to normal cells. Compared to the model group, P.V groups had significantly lower levels of the CRC biomarkers CEA, CA19-9, and CA72-4. Through the evaluation of metabolites and metabolomics, it was found that a total of 50 endogenous metabolites had significant changes. Most of these are modulated and recovered after P.V treatment. It alters glycerol phospholipid metabolites, which are closely related to PI3K target, suggesting that P.V can treat CRC though the PI3K target and PI3K/Akt signaling pathway. q-PCR and Western blot results also verified that the expression of VEGF, PI3K, Akt, P38, JNK, ERK1/2, TP53, IL-6, TNF-α and Caspase-3 were significantly decreased, whereas that of Caspase-9 was increased after treatment. CONCLUSION: P.V is dependent on PI3K target and PI3K/Akt signaling pathway for CRC treatment.

Dynamic evaluation of the cervical spine by kinematic MRI in patients with cervical spinal cord injury without fracture and dislocation.

BACKGROUND: The pattern of changes in the cervical spine and the spinal cord and their dynamic characteristics in patients with cervical spinal cord injury without fracture and dislocation remain unclear. This study aimed to evaluate the dynamic changes in the cervical spine and spinal cord from C2/3 to C7/T1 in different positions by using kinematic magnetic resonance imaging in patients with cervical spinal cord injury without fracture and dislocation. This study was approved by the ethics committee of Yuebei People's Hospital. METHODS: Using median sagittal T2-weighted images for 16 patients with cervical spinal cord injury without fracture and dislocation who underwent cervical kinematic MRI, the anterior space available for the cord, spinal cord diameter, posterior space available for the cord from C2/3 to C7/T1, and Muhle's grade were determined. The spinal canal diameter was calculated by adding the anterior space available for the cord, spinal cord diameter, and posterior space available for the cord. RESULTS: The anterior space available for the cord, posterior space available for the cord, and spinal canal diameters at C2/3 and C7/T1 were significantly higher than those from C3/4 to C6/7. Muhle's grades at C2/3 and C7/T1 were significantly lower than those at the other levels. Spinal canal diameter was lower in extension than in the neutral and flexion positions. In the operated segments, significantly lesser space was available for the cord (anterior space available for the cord + posterior space available for the cord), and the spinal cord diameter/spinal canal diameter ratio was higher than those in the C2/3, C7/T1, and non-operated segments. CONCLUSION: Kinematic MRI demonstrated dynamic pathoanatomical changes, such as canal stenosis in different positions, in patients with cervical spinal cord injury without fracture and dislocation. The injured segment had a small canal diameter, high Muhle's grade, low space available for the cord, and high spinal cord diameter/spinal canal diameter ratio.

Benign goiters requiring thyroidectomy as the signal for PTEN hamartoma tumor syndrome diagnosis.

PTEN hamartoma tumor syndrome (PHTS) is a rare genetic cancer and tumor predisposition syndrome. Due to the wide spectrum of clinical manifestations and variable age at onset, the pathways leading to a PHTS diagnosis are difficult and highly variable. Many patients were found to have PHTS after a cancer diagnosis, missing the opportunity of prevention or enhanced cancer screening. This retrospective study evaluated a PHTS cohort followed in a high-risk surveillance clinic in a comprehensive cancer institution. A significant portion of the patients (60.9%, 14/23) had at least one cancer diagnosis (average age 34.6 years at diagnosis). A significant portion (78.3%, 18/23) were affected with clinically significant goiters (age 27.9 years), and many (60.9%, 14/23) had partial or total thyroidectomy (age 27.1 years). The average age at goiter diagnosis or thyroidectomy is younger than a cancer diagnosis. In 12 individuals who were affected with clinically significant goiter and cancer, all cancers were diagnosed after the thyroid disease (6.3 years). As clinically significant thyroid nodules in childhood or early young adulthood are common in PHTS, but uncommon for general population, these early onset thyroid nodules may alert the clinician to initiate PHTS-targeted evaluation and genetic testing.

Rose Bengal inhibits ß-amyloid oligomers-induced tau hyperphosphorylation via acting on Akt and CDK5 kinases.

RATIONALE: Tau hyperphosphorylation and aggregation is considered as a main pathological mechanism underlying Alzheimer's disease (AD). Rose Bengal (RB) is a synthetic dye used for disease diagnosis, which was reported to inhibit tau toxicity via inhibiting tau aggregation in Drosophila. However, it was unknown if RB could produce anti-AD effects in rodents. OBJECTIVES: The research aimed to investigate if and how RB could prevent ß-amyloid (Aß) oligomers-induced tau hyperphosphorylation in rodents. METHODS AND RESULTS: RB was tested in vitro (0.3-1 µM) and prevented Aß oligomers-induced tau hyperphosphorylation in PC12 cells. Moreover, RB (10-30 mg/kg, i.p.) effectively attenuated cognitive impairments induced by Aß oligomers in mice. Western blotting analysis demonstrated that RB significantly increased the expression of pSer473-Akt, pSer9-glycogen synthase kinase-3ß (GSK3ß) and reduced the expression of cyclin-dependent kinase 5 (CDK5) both in vitro and in vivo. Molecular docking analysis suggested that RB might directly interact with GSK3ß and CDK5 by acting on ATP binding sites. Gene Ontology enrichment analysis indicated that RB might act on protein phosphorylation pathways to inhibit tau hyperphosphorylation. CONCLUSIONS: RB was shown to inhibit tau neurotoxicity at least partially via inhibiting the activity of GSK3ß and CDK5, which is a novel neuroprotective mechanism besides the inhibition of tau aggregation. As tau hyperphosphorylation is an important target for AD therapy, this study also provided support for investigating the drug repurposing of RB as an anti-AD drug candidate.

Inflammatory Myofibroblastic Tumor of the Hilar Bile Duct: A Case Report and Literature Review.

Background: Inflammatory myofibroblastic tumor (IMT) is a very rare tumor and occurs seldom in the biliary tract. IMT can occur in any part of the body and in people of any age; however, it most commonly occurs in children or adolescents. Its etiology and pathogenesis are currently unknown. The clinical manifestations of a hilar inflammatory myofibroblastic tumor are atypical, and the imaging examination is nonspecific. The diagnosis is mainly based on histopathology and immunohistochemistry findings, and surgical resection is the preferred treatment method. Case Description: Herein, we report a rare case of hilar bile duct IMT and review the related literature. Our patient was a 54-year-old woman presenting with a 1-day history of upper abdominal pain as the main clinical symptom. She was misdiagnosed as having cholangiocarcinoma before the surgery. She underwent surgery and was ultimately diagnosed with IMT based on histopathology and immunohistochemistry findings. On 1-year follow-up, no tumor recurrence or related complications were noted. Conclusions: We hope this case report helps clinicians gain a deeper understanding of biliary IMT of the hilum.

Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) refers to one of the top 10 cancers in terms of morbidity and mortality globally, seriously influencing people's lives. First recorded in Compendium of Materia Medica, liquidambaris fructus (LF) generates definite anti-liver tumor effect. However, its effective substances and mechanism remain to be elucidated. Methods: Serum pharmacochemistry and UPLC-QTOF-MS technologies were employed to explore the plasma of rats after intragastric administration of liquidambaris fructus extract (LFE) in order to find the active ingredients. Subsequently, DEN-induced rat liver cancer model was established with the purpose of investigating the anti-tumor activity of LFE from physiological, pathological and biochemical aspects. Finally, non-target metabonomics combined with q-PCR and Western blot methods were adopted for revealing the mechanism. Results: Totally 11 prototype blood transfused ingredients, including imperatorin and phellopterin were detected. LFE presents excellent impact on enhancing the quality of life, prolonging the life cycle, reducing inflammatory reaction, protecting hepatocytes, improving body immunity and killing liver tumor cells. Altogether 82 endogenous differential metabolites were found in metabonomics, suggesting that LFE can treat HCC by acting on key targets of PTEN/PI3K/Akt pathway and fatty acid metabolism. Further research also verified that LFE can upregulate the relative expression levels of PTEN, PDCD4, Caspase 9, Caspase 3, Bax and Bad as well as lower the relative expression levels of PI3K, AKT, VEGFA and Bcl-2. Conclusion: This study revealed the pharmacodynamic material basis of LFE in the treatment of HCC, and from the perspective of metabolomics proved that the effects of inhibiting the growth of tumor cells, promoting tumor cell apoptosis, reducing inflammatory reaction, protecting hepatocytes, improving the survival state of tumor rats, and prolonging the life cycle are related to its impact on PTEN/PI3K/Akt, fatty acid metabolism and other key signal pathways.