Role of autophagy-related genes in liver cancer prognosis.

Autophagy, a highly conserved process of protein and organelle degradation, has emerged as a critical regulator in various diseases, including cancer progression. In the context of liver cancer, the predictive value of autophagy-related genes remains ambiguous. Leveraging chip datasets from the TCGA and GTEx databases, we identified 23 differentially expressed autophagy-related genes in liver cancer. Notably, five key autophagy genes, PRKAA2, BIRC5, MAPT, IGF1, and SPNS1, were highlighted as potential prognostic markers, with MAPT showing significant overexpression in clinical samples. In vitro cellular assays further demonstrated that MAPT promotes liver cancer cell proliferation, migration, and invasion by inhibiting autophagy and suppressing apoptosis. Subsequent in vivo studies further corroborated the pro-tumorigenic role of MAPT by suppressing autophagy. Collectively, our model based on the five key genes provides a promising tool for predicting liver cancer prognosis, with MAPT emerging as a pivotal factor in tumor progression through autophagy modulation.

Development of a Fast Method Using Inductively Coupled Plasma Mass Spectrometry Coupled with High-Performance Liquid Chromatography and Exploration of the Reduction Mechanism of Cr(VI) in Foods.

Hexavalent chromium (Cr(VI)) is known as the most hazardous species of chromium. Speciation analysis of Cr in foods is of a great significance for assessing its influences on human health. In this study, a fast HPLC-ICP-MS method for the determination of Cr(VI) was developed for determining the content of Cr(VI) and also investigating its transformation in foods. The developed method employs an alkali extraction and weak anion-exchange column separation for distinguishing the Cr species, facilitating accurate Cr(VI) quantification within 1.5 min. This technique was applied to determine the Cr(VI) levels in a range of food products, including yoghurt, milk powder, rice flour, orange juice, green tea, white vinegar, and whole wheat bread. The results showed that no Cr(VI) was detected in these food products. Spiking experiments revealed that the recovery rate of Cr(VI) decreased with the increase in its contact time with food products. A further exploration of Cr(VI) in various food components such as vitamin C, tea polyphenols, whey proteins, gelatin, fructose, and cellulose indicated the conversion of Cr(VI) to organic Cr(III) over a period from 20 min to 60 h. It was found that high temperatures and acidic conditions accelerated the rate of Cr(VI) conversion to organic Cr(III) in the six food components mentioned above. This evidence suggests that natural reducing substances in foods probably prevent the occurrence of Cr(VI).

From NAFLD to MASLD: When metabolic comorbidity matters.

INTRODUCTION AND OBJECTIVES: In a recent development, a cohort of hepatologists has proposed altering the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated steatotic liver disease (MASLD), accompanied by modified diagnostic criteria. Our objective was to investigate the effect of the revised definition on identifying significant hepatic fibrosis. PATIENTS AND METHODS: From Jan 2009 to Dec 2022, a total of 428 patients with biopsy-proven hepatic steatosis were diagnosed with NAFLD. Patients were classified into subgroups according to MASLD and Cryptogenic-SLD diagnostic criteria. The clinical pathological features were compared between these two groups. Risk factors for significant fibrosis were analysed in the MASLD group. In total, 329 (76.9 %) patients were diagnosed with MASLD, and 99 (23.1 %) were diagnosed with Cryptogenic-SLD. RESULTS: Those with MASLD exhibited a higher degree of disease severity regarding histology features than Cryptogenic-SLD. The prevalence of significant fibrosis increased from 13 % to 26.6 % for one and two criteria present to 42.5 % for meeting three or more cardiometabolic risk factor (CMRF) criteria (p = 0.001). ALB (aOR:0.94,95 %CI:0.90-1.00; p = 0.030), lower levels of PLT (aOR:0.99, 95 %CI:0.99-1.00; p < 0.001), and more metabolic comorbidities (aOR:1.42,95 %CI:1.14-1.78; p = 0.012) were independent risk factors of significant fibrosis in MASLD. CONCLUSIONS: The new nomenclature of MASLD and SLD is more applicable to identifying significant fibrosis than NAFLD. Patients with three or more cardiometabolic risk factors are at higher risk of fibrosis.

Sucrose Esters and Beeswax Synergize to Improve the Stability and Viscoelasticity of Water-in-Oil Emulsions.

W/O emulsions are commonly used to prepare stable low-fat products, but their poor stability limits widespread applications. In this study, sucrose ester (SE) and beeswax were utilized to prepare an oil dispersion system in rapeseed oil, which was used as the external oil phase to further synergistically construct the W/O emulsion systems. The results show that spherical and fine crystals are formed under the synergistic effect of SE and BW (1.5 SE:0.5 BW). In this state, a dense interfacial crystal layer was easily formed, preventing droplet aggregation, leading to droplet size reduction (1-2 µm) and tight packing, improving viscoelasticity and resistance to deformation, and increasing the recovery rate (52.26%). The long-term stability of W/O emulsions containing up to 60 wt% water was found to be more than 30 days. The increase in the aqueous phase led to droplet aggregation, which increased the viscosity (from 400 Pa·s to 2500 Pa·s), improved the structural strength of the emulsion, and increased the width of the linear viscoelastic region (from 1% strain to 5% strain). These findings provide some technical support for the further development of stable low-fat products.

Dynamic cytokines signature predicts survival outcome from severe Immune-related hepatitis with PD-1/PD-L1 blockade in lung cancer.

BACKGROUND: Immune-related adverse events (irAEs), particularly immune-related hepatitis (IRH) is a potentially serious complication of immune checkpoint inhibitor (ICI) therapy. This retrospective cohort study investigated potential prognostic and predictive biomarkers for IRH. METHOD: This study included 37 patients with advanced lung cancer who received ICIs and were divided into two groups: ≥Grade 3 (G3)-IRH group (n = 17) and without irAE (no-irAE) group (n = 20). Blood samples collected at three different time points and pre-treatment tumor biopsy samples were analyzed using multi-omics assays. RESULTS: The IL-1B RNA expression was significantly increased (limma, fold = 1.94) in the ≥ G3-IRH group than the no-irAE group. Compared with no-irAE group, ≥G3-IRH group had higher monocyte and eosinophil infiltration and lower macrophage infiltration, particularly macrophage M2. Transcriptomics analyses of pre-treatment tumor samples revealed significant upregulation of various inflammation-related genes in the ≥ G3-IRH group (False discovery rate < 0.05). Moreover, various proinflammatory cytokines and chemokines were significantly lower in the plasma of the ≥ G3-IRH group than in the no-irAE group. Subgroup analyses of the ≥ G3-IRH group revealed that plasma IL-1A was significantly higher among those whose IRH resolved than those who had IRH-related death. Patients who died had a greater increase in immune score and Euclidean distance from the baseline to the seventh day of IRH onset, with a dramatic increase in Euclidean distance after immunosuppression, suggesting overstimulated immune status. CONCLUSION: Our study demonstrated the association between IL-1B overexpression and IRH susceptibility. Immune score and Euclidean distance of inflammatory cytokines may provide predictive value on the survival outcome from ≥ G3 IRH.

Repurposing of rilpivirine for preventing platelet ß3 integrin-dependent thrombosis by targeting c-Src active autophosphorylation.

BACKGROUND: HIV-infected individuals are known to be at higher risk for thrombotic cardiovascular disease (CVD), which may also be differentially affected by components of anti-HIV drugs. To identify the effects of a series of FDA-approved anti-HIV drugs on platelet aggregation in humans, focusing on the novel pharmacological effects of rilpivirine (RPV), a reverse transcriptase inhibitor, on platelet function both in vitro and in vivo and the mechanisms involved. METHODS AND RESULTS: In vitro studies showed that RPV was the only anti-HIV reagent that consistently and efficiently inhibited aggregation elicited by different agonists, exocytosis, morphological extension on fibrinogen, and clot retraction. Treatment of mice with RPV significantly prevented thrombus formation in FeCl3-injured mesenteric vessels, postcava with stenosis surgery, and ADP -induced pulmonary embolism models without defects in platelet viability, tail bleeding, and coagulation activities. RPV also improved cardiac performance in mice with post-ischemic reperfusion. A mechanistic study revealed that RPV preferentially attenuated fibrinogen-stimulated Tyr773 phosphorylation of ß3-integrin by inhibiting Tyr419 autophosphorylation of c-Src. Molecular docking and surface plasmon resonance analyses showed that RPV can bind directly to c-Src. Further mutational analysis showed that the Phe427 residue of c-Src is critical for RPV interaction, suggesting a novel interaction site for targeting c-Src to block ß3-integrin outside-in signaling. CONCLUSION: These results demonstrated that RPV was able to prevent the progression of thrombotic CVDs by interrupting ß3-integrin-mediated outside-in signaling via inhibiting c-Src activation without hemorrhagic side effects, highlighting RPV as a promising reagent for the prevention and therapy of thrombotic CVDs.

Copy number variations mediate major pathological response to induction chemo-immunotherapy in unresectable stage IIIA-IIIB lung cancer.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Despite this, evidence supporting optimal management of certain stages remains a topic of debate. In this retrospective study we examine the efficacy and safety, as well as exploring the biomarkers of neoadjuvant induction immuno-chemotherapy, in Chinese patients with unresectable stage III NSCLC. METHODS: Patients with unresectable stage III NSCLC who were identified as driver mutation-negative and who received neoadjuvant chemo-immunotherapy were enrolled from three Chinese hospitals between Jan. 17, 2019, and Jan.17, 2022. Perioperative outcomes and survival data were collected. Retrospective biomarker exploration was performed in available baseline tumor samples and surgical specimens. RESULTS: 94 patients were enrolled and received chemo-immunotherapy as neoadjuvant treatment. 80 patients had squamous cell carcinoma, and 26 had stage IIIB disease. Surgery conversion rate was 74.4%, R0 resection rate was 98.4%. Of 64 patients who underwent surgery, major pathological response (MPR) rate was 65.6% and pathologic complete response (pCR) rate was 42.2%. 73% of patients with N2 disease demonstrated down-staging to N0. Treatment-related adverse events (TRAEs) occurred in 43 patients (45.7%) with anemia was the most common. The Grade ≥ 3 TRAEs rate was 3.2% (3/94). A significant association between copy number variation (CNV) ploidy was also found. CONCLUSION: The combination treatment of immuno-chemotherapy for unresectable stage III NSCLC is not only effective but also has a favourable safety profile. For the first time we provide evidence that CNV status may be a predictive biomarker of MPR.

MMP9-Responsive Graphene Oxide Quantum Dot-Based Nano-in-Micro Drug Delivery System for Combinatorial Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD), especially wet AMD with choroidal neovascularization (CNV), commonly causes blindness in older patients and disruption of the choroid followed by second-wave injuries, including chronic inflammation, oxidative stress, and excessive matrix metalloproteinase 9 (MMP9) expression. Increased macrophage infiltrate in parallel with microglial activation and MMP9 overexpression on CNV lesions is shown to contribute to the inflammatory process and then enhance pathological ocular angiogenesis. Graphene oxide quantum dots (GOQDs), as natural antioxidants, exert anti-inflammatory effects and minocycline is a specific macrophage/microglial inhibitor that can suppress both macrophage/microglial activation and MMP9 activity. Herein, an MMP9-responsive GOQD-based minocycline-loaded nano-in-micro drug delivery system (C18PGM) is developed by chemically bonding GOQDs to an octadecyl-modified peptide sequence (C18-GVFHQTVS, C18P) that can be specifically cleaved by MMP9. Using a laser-induced CNV mouse model, the prepared C18PGM shows significant MMP9 inhibitory activity and anti-inflammatory action followed by antiangiogenic effects. Moreover, C18PGM combined with antivascular endothelial growth factor antibody bevacizumab markedly increases the antiangiogenesis effect by interfering with the "inflammation-MMP9-angiogenesis" cascade. The prepared C18PGM shows a good safety profile and no obvious ophthalmic or systemic side effects. The results taken together suggest that C18PGM is an effective and novel strategy for combinatorial therapy of CNV.

The valuable role of dynamic 18F FDG PET/CT-derived kinetic parameter Ki in patients with nasopharyngeal carcinoma prior to radiotherapy: A prospective study.

BACKGROUND AND PURPOSE: Dynamic positron emission tomography/computed tomography (PET/CT) served the potential role of characterizing malignant foci. The main objective of this prospective study was to explore the advantage of dynamic PET/CT imaging in characterizing nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Patients with probable head and neck disease underwent a local dynamic PET/CT scan followed by a whole-body static scan. Patlak analysis was used to generate parametric influx rate constant (Ki) images from 48 frames obtained from a dynamic PET/CT scan. By delineating the volumes-of-interest (VOIs) of: primary tumor (PT), lymph node (LN), and normal nasopharyngeal tissues (N), we acquired the corresponding Ki mean and SUVmean of each site respectively to perform the quantitative statistical analysis. RESULTS: Qualified images of 71 patients with newly diagnosed NPC and 8 without nasopharyngeal malignant lesions were finally included. We found the correlations between Ki mean-PT and critical clinical features, including clinical stage (r = 0.368), T category (r = 0.643) and EBV-DNA copy status (r = 0.351), and Ki mean-PT differed within the group. SUVmean-PT showed correlations with clinical stage (r = 0.280) and T category (r = 0.472), but could hardly differ systematically within group of clinical features except T category. Ki mean-LN offered the positive correlations with N category (r = 0.294), M category (r = 0.238) and EBV-DNA copy status (r = 0.446), and differed within the group. In addition, Ki mean represented a sensitivity of 94.4 % and a specificity of 100 %, in distinguishing NPC from the non-NPC, when the cut-off was defined as 0.0106. When the cut-off of SUV being defined as 2.03, the sensitivity and specificity were both 100 %. CONCLUSION: Our research confirmed Ki compared favorably to SUV in characterizing NPC and found that Ki can serve as an effective imaging marker of NPC.

Farnesoid-X receptor as a therapeutic target for inflammatory bowel disease and colorectal cancer.

Farnesoid-X receptor (FXR), as a nuclear receptor activated by bile acids, is a vital molecule involved in bile acid metabolism. Due to its expression in immune cells, FXR has a significant effect on the function of immune cells and the release of chemokines when immune cells sense changes in bile acids. In addition to its regulation by ligands, FXR is also controlled by post-translational modification (PTM) activities such as acetylation, SUMOylation, and methylation. Due to the high expression of FXR in the liver and intestine, it significantly influences intestinal homeostasis under the action of enterohepatic circulation. Thus, FXR protects the intestinal barrier, resists bacterial infection, reduces oxidative stress, inhibits inflammatory reactions, and also acts as a tumor suppressor to impair the multiplication and invasion of tumor cells. These potentials provide new perspectives on the treatment of intestinal conditions, including inflammatory bowel disease (IBD) and its associated colorectal cancer (CRC). Moreover, FXR agonists on the market have certain organizational heterogeneity and may be used in combination with other drugs to achieve a greater therapeutic effect. This review summarizes current data on the role of FXR in bile acid metabolism, regulation of immune cells, and effects of the PTM of FXR. The functions of FXR in intestinal homeostasis and potential application in the treatment of IBD and CRC are discussed.

Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial.

BACKGROUND: Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC. MATERIALS AND METHODS: A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate. RESULTS: The incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR. CONCLUSION: Triweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570.

CYP27A1 mutation in a case of cerebrotendinous xanthomatosis: A case report.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive metabolic disease caused by mutations in CYP27A1. It has a low incidence rate, insidious onset, and diverse clinical manifestations. It can be easily misdiagnosed and can go unrecognized by clinicians, leading to delayed treatment and worsened patient outcomes. CASE SUMMARY: A 38-year-old male was admitted to our hospital with a history of unabating unstable posture and difficulty in walking for more than 30 years. Subsequently based on the patient's medical history, clinical symptoms, magnetic resonance imaging and gene sequencing results, he was finally diagnosed with CTX. Due to the low incidence rate of the disease, clinicians have insufficient knowledge of it, which makes the diagnosis process more tortuous and prolongs the diagnosis time. CONCLUSION: Prompt diagnosis and treatment of CTX improve patient outcomes.

Insight of a Metabolic Prognostic Model to Identify Tumor Environment and Drug Vulnerability for Lung Adenocarcinoma.

Metabolic reprogramming is a novel method for the treatment of malignant tumors. The exploration of metabolism procedures between radiosensitive and radioresistant tumors may provide novel perspectives for lung adenocarcinoma (LUAD) patients after radiation therapy. In our study, metabolic reprogramming and immune response changes were found between radioresistant cell line (A549RR) and its parent cells (A549) using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Nucleotide/amino acid, lipid, and glucose metabolic process, including Alanine, aspartate and glutamate metabolism, Tryptophan/Tyrosine metabolism, Butanoate metabolism, Purine/Pyrimidine metabolism, were screened out. Then molecular signatures database and The Cancer Genome Atlas Program (TCGA) lung adenocarcinoma datasets were used to identify metabolism-related genes (MRGs) between radiosensitive and radioresistant lung adenocarcinoma (LUAD) cells. A metabolism-based prognostic model, receiver operating characteristic (ROC) curve and nomogram were constructed using Metabolism Score calculated by 14 metabolism-related genes (MRGs). Three independent public datasets, (GSE72094, GSE3141, GSE8894) and one immunotherapy cohort (IMvigor210) were used as external validation cohorts. Expression of 14 hub genes in cells, normal and LUAD specimens were explored by Human Protein Atlas, TIMER2.0 and RT-qPCR. Patients with low-Metabolism Scores were correlated with longer survival times, higher response rates to immune checkpoint inhibitors (ICIs), different immune cell infiltrations and drug vulnerability. Our study demonstrated a comprehensive landscape between radiosensitive and radioresistant LUAD, and provide novel targets for NSCLC, especially those patients received radiation therapy. Moreover, this metabolism-based prognostic model may help to investigate connections between radiosensitivity, immune response, metabolic reprogramming, and patients' prognosis.

[Efficacy Evaluation of Three Endoscopic Therapies of Isolated Gastric Varices with Modified Tissue Adhesive].

Objective: To evaluate the efficacy of three endoscopic therapies of isolated gastric varices (IGV) with modified tissue adhesive. Methods: A retrospective analysis was conducted with the clinical data of 73 IGV patients who were treated between January 2008 and December 2019 at Beijing Ditan Hospital. Patient clinical data on age, sex, etiology, biochemistry findings, Child-Pugh classification, the type of spontaneous shunt, preoperative bleeding history, and the presence or absence of liver cancer were collected. The three therapies evaluated were endoscopic intravenous injection of tissue glue combined with lauromacrogol, endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, and endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. Their respective clinical treatment outcomes, including ectopic embolism rate, survival rate, rebleeding rate, amount of lauromacrogol and tissue glue used, the number of endoscopic clips used, and the number of times of the procedure the patient underwent, were evaluated. Results: In the patient baseline data, Child-Pugh grade, preoperative thrombus formation, and the presence or absence of liver cancer, showed significant difference between the three therapies ( P<0.05). There was no significant difference in the rates of ectopic embolism among the three methods ( P>0.05), but no ectopic embolism occurred after endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, or after endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. There was no significant difference in the survival rate, the rebleeding rate, amount of lauromacrogol and tissue glue used for the three therapies, but there was significant difference in the number of endoscopic clips used and the number of times the procedure was conducted within one year ( P<0.05). Conclusion: The two endoscopic therapies of intravenous injection of modified tissue glue, one assisted by clip and the other assisted by clip and LOOP, can help reduce the number of procedures IGV patients undergo within one year.

Tumor Microbiome in Nasopharyngeal Carcinoma and Its Association With Prognosis.

Introduction: Previous studies have reported a close relationship between cancer and microbes, particularly gut and tumor microbiota; however, the presence of tumor microbiome in nasopharyngeal carcinoma (NPC) and its role in the prognosis of NPC remain unclear. Methods: We collected 64 samples including tissues from 50 patients with NPC (NPC group) and 14 patients with chronic nasopharyngitis (control group) receiver operating characteristics and we applied 16S ribosome RNA gene sequencing of all samples to assess microbiome profiles and immunohistochemistry to detect tumor microbiome in NPC. Results: Patients in the control group harbored higher species diversity than those in the NPC group; however, the beta diversity was more distinct in the NPC group. In total, three genera with statistically significant differences between the two groups were identified. The area under the receiver operating characteristics (ROC) curve (AUC) was calculated using the relative abundance of these three significant genera, and a value of 0.842 was achieved. Furthermore, Turicibacter was confirmed as a potentially independent prognostic factor for NPC patients, and the progression-free survival (PFS) was markedly prolonged in patients with a low relative abundance of Turicibacter compared to patients with a high relative abundance of this genus (cutoff: 0.0046, hazard ratio: 5.10, 95% confidence interval: 2.04-12.77, p = 0.004). Conclusions: The present study provided strong evidence of a correlation between tumor microbiome and NPC; the tumor microbiome may be considered a biomarker for early NPC diagnosis. Turicibacter potentially served as a independently prognostic indicator for NPC patients.

[Effect of moxibustion combined with acupoint catgut embedding on IL-6/JAK/STAT3 signaling pathway in colonic mucosa of ulcerative colitis rats].

OBJECTIVE: To observe the effect of moxibustion combined with acupoint catgut embedding on the content of interleukin 6 (IL-6), and the expressions of janus activated kinase (JAK), signal transducer and activator of transcription 3 (STAT3) in colonic mucosa of rats with ulcerative colitis (UC), so as to explore its mechanism underlying improvement of UC. METHODS: Thirty SD rats were randomly divided into normal, model, acupoint catgut embedding (ACE), moxibustion and acupoint catgut embedding combined with moxibustion (combination) groups (n=6 rats in each group). The UC model was established by enema of trinitro-benzene-sulfonic acid and ethanol. Moxibustion was applied to bilateral "Tianshu" (ST25), "Dachangshu" (BL25) and "Shangjuxu" (ST37) for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, colonic mucosal pathological changes were observed by H.E. staining, the level of IL-6 in colonic mucosa was assayed by ELISA, and the expressions of JAK and STAT3 in colonic mucosa were detected by immunohistochemistry and Western blot. RESULTS: H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and combination groups. After modeling, the content of colonic IL-6, and the expression levels of JAK and STAT3 were obviously increased (P<0.01) in the model group relevant to the normal group. Following the intervention, the increase of IL-6 contents, and JAK and STAT3 expressions were reversed (P<0.05, P<0.01) in moxibustion, ACE and combination groups. The therapeutic effects of moxibustion combined with ACE were considerably superior to those of simple ACE and simple moxibustion in down-regulating the levels of JAK and STAT3 expression (P<0.01). CONCLUSION: Acupoint catgut embedding combined with moxibustion can repair the injured colonic mucosa of UC rats, which may be related with its effect in suppressing the activation of IL-6/JAK/STAT3 signaling pathway.

The efficacy of vitamin D in treatment of fibromyalgia: a meta-analysis of randomized controlled studies and systematic review.

BACKGROUND AND AIMS: Recent studies have found potential benefits of vitamin D in relieving pain, and the results from randomized controlled trials of vitamin D for fibromyalgia have been promising. We conducted a comprehensive systematic review and meta-analysis to evaluate the efficacy of vitamin D for treating fibromyalgia. RESEARCH DESIGN AND METHODS: PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for English-language articles. Based on the inclusion and exclusion criteria, we selected only randomized controlled studies that reported vitamin D versus placebo-controlled cure for fibromyalgia. After extracting valid data, a meta-analysis was performed using Stata 12.0. The major outcome in the pooled analysis was the Fibromyalgia Impact Questionnaire and Visual Analogue Scale (VAS) changes. RESULTS: Five studies including 315 participants were identified. These studies found that vitamin D was effective in reducing Fibromyalgia Impact Questionnaire scores compared with those of the control group, with significant differences (weighted mean difference = -7.82, 95% confidence interval: -12.05 to -3.59, P < 0.001). However, there was no statistical difference in VAS between the two groups (weighted mean difference = -0.60, 95% confidence interval: -1.38 to 0.17, P > 0.05). CONCLUSIONS: Vitamin D supplementation may be an effective fibromyalgia therapeutic approach.

The efficacy and safety of albumin-bound paclitaxel plus carboplatin as neoadjuvant therapy for potentially resectable lung squamous cell carcinoma: a real-world retrospective cohort study.

Background: In early and locally advanced stage non-small-cell lung cancer (NSCLC), surgery is the cornerstone of curative-intent treatments. And the addition of neoadjuvant or adjuvant chemotherapy can prolong overall survival (OS), albumin-bound paclitaxel plus carboplatin (ab-PC) as neoadjuvant therapy (NAT) has showed favorable effect for resectable lung squamous cell carcinoma (LSCC) with IIIA. However, to date, no study has investigated the efficacy of ab-PC as neoadjuvant chemotherapy in potentially resectable LSCC with IIIA-IIIB. This study aimed to evaluate the efficacy and safety of the regimen in potentially resectable LSCC. Methods: Enrolled patients with stage IIIA and IIIB potentially resectable LSCC treated with neoadjuvant albumin-bound paclitaxel (nab-P; 100 mg/m2, days 1, 8, and 15) and carboplatin (6 mg/mL/min, day 1) for two 21-day cycles at the Hunan Cancer Hospital between December 2017 and December 2019. The primary endpoint was the surgery conversion rate (SCR). Secondary endpoints included objective response rate (ORR), margin-free (R0) resection, major pathological response (mPR), and safety. Results: In total, 49 patients were included in the study, with an overall response rate (ORR) of 67% (33/49). The SCR was 67% (33/49). Only 31 patients underwent surgery eventually, and R0 resection was achieved in 30 patients. Further, 4 (13%) and 11 (35%) of the 31 patients had a pathological complete response (pCR) and mPR, respectively. In total, 23 patients experienced treatment-related adverse events (TRAEs). The most common TRAE was liver disfunction (9 patients, 18%). Only 1 patient (2%) experienced a grade ≥3 TRAE of leukopenia. There were no treatment-related deaths or treatment discontinuations. Conclusions: In this study, we found a high SCR (67%) and mPR (35%) after ab-PC treatment for stage IIIA and IIIB potentially resectable LSCC. ab-PC maybe considered a neoadjuvant chemotherapy option for potentially resectable LSCC patients.

Investigation on the survival implications of PD-L1 expression status in ALK- rearranged advanced non-small cell lung cancer treated with first-line crizotinib.

BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression has been associated with shorter progression-free survival (PFS) of crizotinib-treated patients with anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC). However, the association between PD-L1 expression and overall survival (OS) in ALK-rearranged NSCLC remains unclear. In this study, we investigated the survival implication of baseline PD-L1 expression status in crizotinib-treated patients with ALK-rearranged advanced NSCLC. METHODS: Between October 1, 2015, and October 31, 2021, we retrospectively analyzed the baseline PD-L1 expression levels using immunohistochemistry 22C3 assay of tissue samples from 128 patients with ALK-rearranged advanced lung adenocarcinoma who were treated with first-line crizotinib. RESULTS: Of the 128 baseline tumor specimens analyzed, a majority (76.6%, n = 98) had low PD-L1 expression (tumor proportion score (TPS) < 50%), wherein 58.6% (n = 75) had < 1% and 18.0% (n = 23) had 1%-49%, and the remaining 23.4% (n = 30) had high PD-L1 expression level (TPS ≥ 50%). High baseline PD-L1 expression was not associated with any clinical characteristic examined. Patients with high baseline PD-L1 (n = 30) expression level had significantly shorter median PFS (6 vs 11 months, p = 0.011) and OS (17 vs 53 months, p = 0.023) on crizotinib treatment than those with low PD-L1 level (n = 98). CONCLUSIONS: A subset of patients with ALK-rearranged NSCLC having high baseline PD-L1 expression level (TPS of ≥ 50%) had poorer survival outcomes despite crizotinib therapy. Our study raises the need to investigate alternative treatment strategies to improve survival outcomes of this patient subset.

Clinical Characteristics and Prognosis of Small Cell Carcinoma in the Nasopharynx: A Population-Based Study.

BACKGROUND: Nasopharyngeal small cell carcinoma (SmCC) is a rare histological type of nasopharyngeal cancer, and its prognosis remains poor. This study aimed to determine the clinical characteristics and survival prognostic factors of nasopharyngeal SmCC. METHODS: Detailed clinicopathologic and therapeutic characteristics of a patient diagnosed with nasopharyngeal SmCC were determined. Nasopharyngeal SmCC cases reported previously were reviewed and summarized. Furthermore, a retrospective analysis was performed on data from the Surveillance, Epidemiology, and End Results (SEER) Program database. Kaplan-Meier analysis was conducted to compare survival within groups. Univariate and multivariate analyses were performed to investigate prognostic factors. RESULTS: A nasopharyngeal SmCC patient treated with chemoradiotherapy who achieved 46 months long-term survival was reported. In reviewing 16 reported cases with epidemiologic and therapeutic details, we found most of nasopharyngeal SmCC patients were diagnosed with advanced grades and received chemoradiotherapy. In total, 13,993 cases of nasopharyngeal cancer were extracted from the SEER database, from which 57 nasopharyngeal SmCC cases were eventually screened out. The mean age of the patients was 55.70 years, and 64.9% of these cases were either grade III or IV; the median overall survival (OS) was 18 months. Statistically significant differences were observed in the OS values of groups categorized by age (P = .025) or radiotherapy (P = .037). Age (<70 years) and radiotherapy were identified as independent survival and prognostic factors. CONCLUSION: Patients with nasopharyngeal SmCC are usually diagnosed with advanced grades and have poor prognoses; nevertheless, they can benefit from radiotherapy with prolonged overall survival.