Clinical study of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases. We categorize acute pancreatitis by etiology into acute biliary pancreatitis (ABP) and hypertriglyceridemia-induced acute pancreatitis (HTGP). AIM: To investigate the clinical significance of NLR and PLR in assessing persistent organ failure (POF) in HTGP and ABP. METHODS: A total of 1450 patients diagnosed with acute pancreatitis (AP) for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled. The patients were categorized into two groups according to the etiology of AP: ABP in 530 patients and HTGP in 241 patients. We collected and compared the clinical data of the patients, including NLR, PLR, and AP prognostic scoring systems, within 48 h of hospital admission. RESULTS: The NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In the HTGP group, both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score ≥ 3. Likewise, in the ABP group, NLR and PLR were significantly elevated in patients with severe AP, modified computed tomography severity index score ≥ 4, Japanese Severity Score ≥ 3, and modified Marshall score ≥ 2. Moreover, NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups. CONCLUSION: NLR and PLR vary between ABP and HTGP, are strongly associated with AP prognostic scoring systems, and have predictive potential for the occurrence of POF in both ABP and HTGP.

N6-methyladenosine modified TGFB2 triggers lipid metabolism reprogramming to confer pancreatic ductal adenocarcinoma gemcitabine resistance.

Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.

Understanding variants of unknown significance: the computational frontier.

The rapid advancement of sequencing technologies has led to the identification of numerous mutations in cancer genomes, many of which are variants of unknown significance (VUS). Computational models are increasingly being used to predict the functional impact of these mutations, in both coding and noncoding regions. Integration of these models with emerging genomic datasets will refine our understanding of mutation effects and guide clinical decision making. Future advancements in modeling protein interactions and transcriptional regulation will further enhance our ability to interpret VUS. Periodic incorporation of these developments into VUS reclassification practice has the potential to significantly improve personalized cancer care.

Transcriptome analysis reveals the role of Long noncoding RNAs (lncRNA) in specific deposition of inosine monphosphate in Jingyuan chickens.

Inosine monphosphate (IMP) is one of the important indicators for evaluating meat flavor, and long noncoding RNAs (lncRNAs) play an important role in its transcription and post-transcriptional regulation. Currently, there is little information about how lncRNA regulates the specific deposition of IMP in chicken muscle. In this study, we used transcriptome sequencing to analyze the lncRNAs of the breast and leg muscles of the Jingyuan chicken and identified a total of 357 differentially expressed lncRNAs (DELs), of which 158 were up-regulated and 199 were down-regulated. There were 2,203 and 7,377 cis- and trans-regulated target genes of lncRNAs, respectively, and we identified the lncRNA target genes that are involved in NEGF signaling pathway, glycolysis/ glucoseogenesis and biosynthesis of amino acids pathways. Meanwhile, 621 pairs of lncRNA-miRNA-mRNA interaction networks were constructed with target genes involved in purine metabolism, fatty acid metabolism, and biosynthesis of amino acids. Next, three interacting meso-networks gga-miR-1603-LNC_000324-PGM1, gga-miR-1768-LNC_000324-PGM1 and gga-miR-21-LNC_011339- AMPD1 were identified as closely associated with IMP-specific deposition. Both differentially expressed genes (DEGs) PGM1 and AMPD1 were significantly enriched in IMP synthesis and metabolism-related pathways, and participated in the anabolic process of IMP in the form of organic matter synthesis and energy metabolism. This study obtained lncRNAs and target genes affecting IMP-specific deposition in Jingyuan chickens based on transcriptome analysis, which deepened our insight into the role for lncRNAs in chicken meat quality.

Effects of transcutaneous electrical acupoint stimulation on early postoperative pain and recovery: a comprehensive systematic review and meta-analysis of randomized controlled trials.

Background: Previous studies have indicated beneficial outcomes of transcutaneous electrical acupoint stimulation (TEAS), but high-quality and comprehensive meta-analyses are lacking. The aim was to quantitatively analyze the efficacy and safety of perioperative TEAS on postoperative pain and recovery. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched through July 2022. Randomized controlled trials (RCTs) that examined the perioperative application of TEAS in adults compared with sham-TEAS and/or non-TEAS were eligible. Cumulative analgesic consumption within 24 h and rest pain scores at 2, 6, 12, and 24 h postoperatively were the two co-primary outcomes. Results: Seventy-six RCTs (n = 9,665 patients) were included. Patients treated with TEAS experienced a reduction in clinical importance in cumulative analgesic (morphine equivalent) consumption (WMD: -14.60 mg, 97.5% CI: -23.60 to -5.60; p < 0.001) and a reduction in statistical importance in rest pain scores at multiple time points within the first 24 postoperative hours. The secondary outcome analysis also identified clinically significant recovery benefits to TEAS during the first 24 h after surgery. Furthermore, TEAS could effectively reduce opioid-related side effects and did not increase serious side effects. Conclusion: This article describes current evidence about TEAS intervention on early postoperative pain and recovery. The results support the effectiveness of TEAS, but more high-quality evidence of clinical applicability is also needed. Systematic review registration: PROSPERO (CRD42021249814).

Strain controllable band alignment and the interfacial and optical properties of tellurene/GaAs van der Waals heterostructures.

By using first principles calculations, we theoretically investigate the electronic structures and the interfacial and optical properties of the two-dimensional tellurene (Te)-gallium arsenide (GaAs) van der Waals heterostructures (vdWHs), i.e., α-Te/GaAs and γ-Te/GaAs, formed using Te and GaAs monolayers. It has been demonstrated that, the semiconductor-semiconductor contacted α-Te/GaAs vdWH exhibits a type-II band alignment with a direct band gap of 0.28 eV while the metal-semiconductor contacted γ-Te/GaAs vdWH has a p-type Schottky contact with a Schottky barrier height (SBH) of 0.36 eV at the interface. The transition from type-II to type-III band alignment is observed firstly in the α-Te/GaAs vdWH when the in-plane biaxial strain is less than -5.2% and larger than 4.4%, meanwhile, the p-type Schottky contact to Ohmic contact transition may be realized in the γ-Te/GaAs vdWH when the in-plane biaxial strain is less than -2.4%. Finally, the maximum optical absorption coefficients of the α- and γ-Te/GaAs vdWHs have been found to be up to 31% and 29%, respectively, and may be modulated effectively by applying in-plane biaxial strain. The obtained results may be of importance in the design of nanoelectronic devices based on the proposed tellurene/GaAs vdWHs.

Saliva­microbiome­derived signatures: expected to become a potential biomarker for pulmonary nodules (MCEPN-1).

BACKGROUND: Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical stage for the early detection of lung cancer; however, the relationship between oral microbiota and PNs remains unknown. METHODS: We conducted a 'Microbiome with pulmonary nodule series study 1' (MCEPN-1) where we compared PN patients and healthy controls (HCs), aiming to identify differences in oral microbiota characteristics and discover potential microbiota biomarkers for non-invasive, radiation-free PNs diagnosis and warning in the future. We performed 16 S rRNA amplicon sequencing on saliva samples from 173 PN patients and 40 HCs to compare the characteristics and functional changes in oral microbiota between the two groups. The random forest algorithm was used to identify PN salivary microbial markers. Biological functions and potential mechanisms of differential genes in saliva samples were preliminarily explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of Orthologous Groups (COG) analyses. RESULTS: The diversity of salivary microorganisms was higher in the PN group than in the HC group. Significant differences were noted in community composition and abundance of oral microorganisms between the two groups. Neisseria, Prevotella, Haemophilus and Actinomyces, Porphyromonas, Fusobacterium, 7M7x, Granulicatella and Selenomonas were the main differential genera between the PN and HC groups. Fusobacterium, Porphyromonas, Parvimonas, Peptostreptococcus and Haemophilus constituted the optimal marker sets (area under curve, AUC = 0.80), which can distinguish between patients with PNs and HCs. Further, the salivary microbiota composition was significantly correlated with age, sex, and smoking history (P < 0.001), but not with personal history of cancer (P > 0.05). Bioinformatics analysis of differential genes showed that patients with PN showed significant enrichment in protein/molecular functions related to immune deficiency and energy metabolisms, such as the cytoskeleton protein RodZ, nicotinamide adenine dinucleotide phosphate dehydrogenase (NADPH) dehydrogenase, major facilitator superfamily transporters and AraC family transcription regulators. CONCLUSIONS: Our study provides the first evidence that the salivary microbiota can serve as potential biomarkers for identifying PN. We observed a significant association between changes in the oral microbiota and PNs, indicating the potential of salivary microbiota as a new non-invasive biomarker for PNs. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR2200062140; Date of registration: 07/25/2022.

Thermally Activated Delayed Fluorescence with Nanosecond Emission Lifetimes and Minor Concentration Quenching: Achieving High-Performance Nondoped and Doped Blue OLEDs.

Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.

PKM2 promotes myoblast growth and inosine monophosphate-specific deposition in Jingyuan chicken.

Inosine monophosphate (IMP) is widely regarded as an important indicator for evaluating the flavour of poultry meat. However, little is known about the molecular mechanisms affecting the specific deposition of IMP. In this study, we functionally verified PKM2 (Pyruvate kinase M2), a candidate gene related to IMP synthesis, in order to reveal the important role of PKM2 in meat flavour and muscle development of Jingyuan chickens. The results showed that the IMP content in breast muscle of Jingyuan chickens was negatively correlated with PKM2 mRNA expression (r = -0.1710), while the IMP content in leg muscle was significantly positively correlated with PKM2 mRNA expression (r = 0.7350) (P < 0.05). During myogenesis, PKM2 promoted the proliferation rate of myoblasts and the expression of proliferation marker genes, inhibited the apoptosis rate and the expression of apoptosis marker genes, and decreased the expression of differentiation marker genes. Up-regulation of PKM2 enhanced the expression of key genes in the purine metabolic pathway and the de novo synthesis pathway of IMP, and suppressed the expression of key genes in the salvage pathway. ELISA assays showed that PKM2 decreased IMP and hypoxanthine (HX) contents, while adenosine triphosphate (ATP) and uric acid (UA) contents were clearly elevated. In summary, these studies revealed that PKM2 regulates myogenesis and specific deposition of IMP, which can be used to improve the quality of Jingyuan chicken meat.

Association of depressive symptom severity and suicidal ideation with health-related quality of life among stroke survivors, NHANES 2005-2018.

Stroke, a critical health issue in the US, not only has physical repercussions but also potentially affects the health-related quality of life (HRQoL) through neuropsychiatric outcomes like depressive symptoms and suicidal thoughts. This study utilized a nationally representative sample of 1302 US stroke survivors (age ≥ 20) from the US National Health and Nutrition Examination Survey (2005-2018) to assessed relationships between QoL via the CDC HRQOL-4 and evaluated depressive symptoms and suicidal ideation using the Patient Health Questionnaire-9 (PHQ-9). Participants (mean age: 64.4; 56.0 % female) showed that 40.7 % had at least mild depressive symptoms, and 18.8 % exhibited major depressive symptoms. Suicidal ideation was reported by 8.1 %. After sociodemographic and health condition adjustments, mild and major depressive symptoms, along with suicidal ideation, were associated with poorer general health status and more physically and mentally unhealthy days and activity limitation days. A dose-response relationship between PHQ-9 scores and HRQoL outcomes was evident (All P for trend <0.001). Stroke survivors with suicidal ideation also experienced more physically and mentally unhealthy days and activity limitation days. Depressive symptoms and suicidal ideation are associated with reduced HRQoL among US stroke survivors, underscoring the importance of thorough neuropsychiatric evaluations and interventions to bolster stroke survivors' well-being.

East Asia Superciliary Arch Augmentation With Silicone Implant.

OBJECTIVE: A flat superciliary arch is relatively common in East Asian women. Superciliary arch augmentation aims to increase the facial three-dimensionality of the upper face. However, there are few reports in the literature specifically introducing the surgery. In this study, the authors present the clinical outcomes after a series of superciliary arch augmentation with silicone implants. METHODS: From May 2020 to December 2022, 54 patients underwent superciliary arch augmentation with silicone implants. Silicone implants generally have a length of 50 to 60 mm, a width of 13 to 14 mm, and an arc of 170 degrees. The thickness was 2 to 7 mm. The implant was placed subperiosteal at the lower edges of the eyebrows through a 7 mm incision below the brow tail. All patients evaluated the outcome according to the Global Esthetic Improvement Scale. Four plastic surgeons evaluated postsurgery results with a 5-point Likert Scale (5 = excellent, 4 = good, 3 = fair, 2 = no change, and 1 = worse). RESULTS: Fifty-four patients were successfully enrolled. The mean follow-up period was 12.02 ± 3.38 months. The mean thickness was 4.55 ± 0.67 mm for the thickest part of the implant. The minor complication rate was 44.44%. They all subsided within 1 month without treatment. Patients' outcome ratings were 4.45 ± 0.55 (3 mo), 4.51 ± 0.48 (6 mo), and 4.51 ± 0.45 (1 y). The surgeons' outcome scoring was 4.49 ± 0.31. CONCLUSIONS: Superciliary arch augmentation with silicone implants is a quite simple, effective, inexpensive, and safe strategy to improve the three-dimensionality and contour of the upper face in East Asians.

Influence of nutritional supplements on antibody levels in pregnant women vaccinated with inactivated SARS-CoV-2 vaccines.

BACKGROUND: Because of the significantly higher demand for nutrients during pregnancy, pregnant women are more likely to have nutrient deficiencies, which may adversely affect maternal and fetal health. The influence of nutritional supplements on the immune effects of inactivated SARS-CoV-2 vaccines during pregnancy is not clear. METHODS: In a multicenter cross-sectional study, we enrolled 873 pregnant women aged 18-45 y in Guangdong, China. The general demographic characteristics of pregnant women and their use of nutritional supplements were investigated, and the serum antibody levels induced by inactivated SARS-CoV-2 vaccines were measured. A logistic regression model was used to analyze the association between nutritional supplements and SARS-CoV-2 antibody levels. RESULTS: Of the 873 pregnant women enrolled, 825 (94.5%) took folic acid during pregnancy, 165 (18.9%) took iron supplements, and 197 (22.6%) took DHA. All pregnant women received at least one dose of inactivated SARS-CoV-2 vaccine, and the positive rates of serum SARS-CoV-2 neutralizing antibodies (NAbs) and immunoglobulin G (IgG) antibodies were 44.7% and 46.4%, respectively. After adjustment for confounding factors, whether pregnant women took folic acid, iron supplements, or DHA did not influence NAb positivity or IgG positivity (P > 0.05). Compared with pregnant women who did not take folic acid, the odds ratios (ORs) for the presence of SARS-CoV-2 NAb and IgG antibody in pregnant women who took folic acid were 0.67 (P = 0.255; 95% CI, 0.34-1.32) and 1.24 (P = 0.547; 95% CI, 0.60-2.55), respectively. Compared with pregnant women who did not take iron supplements, the ORs for the presence of NAb and IgG antibody in pregnant women who took iron supplements were 1.16(P = 0.465; 95% CI, 0.77-1.76) and 0.98 (P = 0.931; 95% CI, 0.64-1.49), respectively. Similarly, the ORs for NAb and IgG antibody were 0.71 (P = 0.085; 95% CI, 0.49-1.04) and 0.95 (P = 0.801; 95% CI, 0.65-1.38) in pregnant women who took DHA compared with those who did not. CONCLUSIONS: Nutritional supplementation with folic acid, iron, or DHA during pregnancy was not associated with antibody levels in pregnant women who received inactivated SARS-CoV-2 vaccines.

Vitexin enhances radiosensitivity of mouse subcutaneous xenograft glioma by affecting the miR-17-5p/miR-130b-3p/PTEN/HIF-1α pathway.

PURPOSE: Vitexin can cooperate with hyperbaric oxygen to sensitize the radiotherapy of glioma by inhibiting the hypoxia-inducible factor (HIF)-1α. However, whether vitexin has a direct radiosensitization and how it affects the HIF-1α expression remain unclear. This study investigated these issues. METHODS: The SU3 cells-inoculated nude mice were divided into control, radiation, and vitexin + radiation groups. The vitexin + radiation-treated mice were intraperitoneally injected with 75 mg/kg vitexin daily for 21 days. On the 3rd, 10th, and 17th days during the vitexin treatment, the radiation-treated mice were locally irradiated with 10 Gy, respectively. In vitro, the microRNA (miR)-17-5p or miR-130b-3p mimics-transfected SU3 cells were used to examine the effects of vitexin plus radiation on expression of miR-17-5p- or miR-130b-3p-induced radioresistance-related pathway proteins. The effects of vitexin on miR-17-5p and miR-130b-3p expression in SU3 cells were also evaluated. RESULTS: Compared with the radiation group, the tumor volume, tumor weight, and expression of HIF-1α, vascular endothelial growth factor, and glucose transporter-1/3 proteins, miR-17-5p, and miR-130b-3p in tumor tissues in the vitexin + radiation group decreased, whereas the expression of phosphatase and tensin homolog (PTEN) protein increased. After treatment of miR-17-5p or miR-130b-3p mimics-transfected SU3 cells with vitexin plus radiation, the PTEN protein expression also increased, the HIF-1α protein expression decreased correspondingly. Moreover, vitexin decreased the miR-17-5p and miR-130b-3p expression in SU3 cells. CONCLUSION: Vitexin can enhance the radiosensitivity of glioma, and its mechanism may partly be related to the attenuation of HIF-1α pathway after lowering the inhibitory effect of miR-17-5p and miR-130b-3p on PTEN.

Risk factors and the CCTA application in patients with vulnerable coronary plaque in type 2 diabetes: a retrospective study.

BACKGROUND: Diabetes is an independent risk factor for cardiovascular disease. The purpose of this study was to identify the risk factors for vulnerable coronary plaques (VCPs), which are associated with adverse cardiovascular events, and to determine the value of coronary CT angiography (CCTA) in patients with type 2 diabetes mellitus (T2DM) and VCPs. METHODS: Ninety-eight T2DM patients who underwent CCTA and intravascular ultrasound (IVUS) were retrospectively included and analyzed. The patients were grouped and analyzed according to the presence or absence of VCPs. RESULTS: Among the patients with T2DM, time in range [TIR {the percentage of time blood glucose levels were in the target range}] (OR = 0.93, 95% CI = 0.89-0.96; P < 0.001) and the high-density lipoprotein-cholesterol (HDL-C) concentration (OR = 0.24, 95% CI = 0.09-0.63; P = 0.04) were correlated with a lower risk of VCP, but the triglycerides (TG) concentration was correlated with a higher risk of VCP (OR = 1.79, 95% CI = 1.01-3.18; P = 0.045). The area under the receiver operator characteristic curve (AUC) of TIR, and HDL-C and TG concentrations were 0.76, 0.73, and 0.65, respectively. The combined predicted AUC of TIR, and HDL-C and TG concentrations was 0.83 (P < 0.05). The CCTA sensitivity, specificity, false-negative, and false-positive values for the diagnosis of VCP were 95.74%, 94.12%, 4.26%, and 5.88%, respectively. The identification of VCP by CCTA was positively correlated with IVUS (intraclass correlation coefficient [ICC] = 0.90). CONCLUSIONS: The TIR and HDL-C concentration are related with lower risk of VCP and the TG concentration was related with higher risk of VCP in patients with T2DM. In clinical practice, TIR, HDL-C and TG need special attention in patients with T2DM. The ability of CCTA to identify VCP is highly related to IVUS findings.

Effects of yoga on clinical symptoms, quality of life and social functioning in patients with schizophrenia: A systematic review and meta-analysis.

BACKGROUND: Yoga is gradually being explored as a potential complementary intervention in addition to psychiatric drugs for schizophrenia. However, there are conflicts on the efficacy of yoga for schizophrenia. This meta-analysis was aimed to evaluate the association of yoga intervention with reductions on clinical symptoms and improvements in quality of life (QoL) as well as social functioning among schizophrenia. METHOD: Systematic literature search was undertaken to identify all RCTs that compared yoga with active or passive controls for patients with schizophrenia from inception to July 2023. The outcomes were measurements of positive symptoms, negative symptoms, QoL and social functioning. Random-effects models were performed to calculate the effect sizes in the standardized mean differences reporting as Hedges' s g statistic. RESULTS: 19 studies enrolling 1274 participants with schizophrenia were included. Yoga had a medium effect on positive symptoms in the short term (Hedges's g = 0.31) and small effect in the long term (Hedges's g = 0.18). Medium significant effects were also found on negative symptoms in both the short term (Hedges's g = 0.44) and the long term (Hedges's g = 0.35). Yoga had a significant impact on improving both total QoL (Hedges's g = 0.34) and social functioning (Hedges's g = 0.45) with medium effect sizes. CONCLUSIONS: Yoga was associated with significant reductions on negative and positive symptoms, and significant improvements in QoL as well as social functioning in patients with schizophrenia. Future research should explore the long-term efficacy of yoga for schizophrenia, encompassing more diverse populations.

Herbal medicine for the prevention of chemotherapy-induced nausea and vomiting in patients with advanced colorectal cancer: A prospective randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine is increasingly used as complementary therapy to manage nausea and vomiting in different cultures. One such herbal recipe is the Hezhong granules, which contain classical antiemetic formulations, and are commonly used to prevent chemotherapy-induced nausea and vomiting (CINV). Modern pharmacological studies have shown that the key components of Hezhong granules, including Pinellia ternata (Thunb.), Evodia rutaecarpa (Juss.), and Zingiber officinale exhibit significant antiemetic and antitumor properties. Despite this promising evidence, controlling CINV remains a significant challenge in cancer treatment. Moreover, there is a lack of scientifically designed clinical trials to validate the efficacy and safety of classical antiemetic formulas for CINV interventions. AIMS OF THE STUDY: To investigate the efficacy and safety of Hezhong granules in preventing CINV in patients with advanced colorectal cancer (CRC). METHODS: This study was conducted between October 2020 and February 2022 in 12 hospital wards in Southwest China. In this multicenter, randomized controlled trial, we enrolled patients with advanced CRC who received fluorouracil-based chemotherapy. The patients were randomly assigned in a 1:1 ratio to either the Hezhong granule group (receiving a 5-HT3-receptor antagonist, dexamethasone, and Hezhong granules) or the placebo group (receiving a 5-HT3-receptor antagonist, dexamethasone, and placebo) during the first and second courses of chemotherapy. A 5-day diary was provided to all patients. Acute and delayed CINV were defined as CINV occurring within 24 h or between 24 and 120 h after the start of treatment. The primary endpoints were complete response rate (CRR, defined as the proportion of patients without nausea/vomiting) and objective response rate (ORR, defined as the proportion of patients without nausea/vomiting plus mild nausea/vomiting) for both acute and delayed CINV. Secondary endpoints were the daily rates of CINV events and Functional Living Index-Emesis (FLIE). To identify the predictors of CINV, we conducted multivariate ordered logistic regression analysis. This study was registered with the Chinese Clinical Trial, number ChiCTR2100041643. RESULTS: A total of 120 participants were randomly assigned, of whom 112 (56/56) completed two cycles and were included in the full analysis. In the acute phase, there were minor improvements in the Hezhong granule group, but there were no significant differences in the CRRs for nausea and vomiting (mean difference:10.7 %, P = 0.318, 0.324), while the ORRs increased by approximately 17.5 % (mean difference:16.1 %, P = 0.051; 17.9 %, P = 0.037, respectively). In the delayed phase, significant improvements of approximately 20 % were observed in both the CRRs (mean difference:19.6 %, P = 0.053; 21.4 %, P = 0.035) and ORRs (mean difference:17.9 %, P = 0.037, 0.043) for nausea and vomiting. Additionally, the daily rate of CINV events showed a mean difference of 19 % (P < 0.05). According to FLIE scores, approximately 70 % of patients who received Hezhong granules reported an improvement in their quality of life, with CINV symptoms having"no impact on daily life (NIDL)". No serious adverse events were attributed to herbal medicine. CONCLUSIONS: Hezhong granules proved to be both effective and well-tolerated in preventing CINV in patients with advanced CRC, with notable benefits in preventing delayed CINV. These promising results set the stage for subsequent phase III clinical trials and experimental research on Hezhong Granules.

The Spatial Relationship Between Coronoid Process and Zygomatic Complex After Reduction Malarplasty.

BACKGROUND: Reduction malarplasty presents challenges in terms of postoperative complications, particularly limited mouth opening. Excessive inward displacement of the zygomatic complex can impinge on the coronoid process resulting in restricted mouth opening. This study aimed to assess the spatial relationship between the coronoid process and the zygomatic complex after reduction malarplasty. METHODS: A retrospective study was conducted, including consecutive patients underwent reduction malarplasty. Radiological measurements were performed before surgery and during the final follow-up, including the coronoid-condylar index, distance between the coronoid process and zygomatic complex, and thickness and density of the temporal and masseter muscles. Clinical and radiographic data were recorded and analyzed. RESULTS: A total of 159 female patients were included with an average age of 28.1 years and a mean follow-up of 6.7 months. The mean coronoid-condylar index was 1:1.4, ranging from 1:0.6 to 1:2.6. Following surgery, the distances between the coronoid process and the anterior zygoma decreased by approximately 1 mm. Additionally, the postoperative distance between the highest point of the coronoid process and the zygomatic arch decreased by around 4 mm horizontally and changed approximately 1 mm vertically. No significant changes were observed in the thickness and density of the temporal and masseter muscles after surgery. CONCLUSIONS: Reduction malarplasty led to a slight decrease in the distance between the coronoid process and the zygoma. The operation generally resulted in proximity between the highest point of the coronoid process and the zygomatic arch. However, we believe that common reduction malarplasty rarely leads to osseous impingement. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

CSNK2A1 confers gemcitabine resistance to pancreatic ductal adenocarcinoma via inducing autophagy.

Gemcitabine, a pivotal chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC), frequently encounters drug resistance, posing a significant clinical challenge with implications for PDAC patient prognosis. In this study, employing an integrated approach involving bioinformatic analyses from multiple databases, we unveil CSNK2A1 as a key regulatory factor. The patient-derived xenograft (PDX) model further substantiates the critical role of CSNK2A1 in gemcitabine resistance within the context of PDAC. Additionally, targeted silencing of CSNK2A1 expression significantly enhances sensitivity of PDAC cells to gemcitabine treatment. Mechanistically, CSNK2A1's transcriptional regulation is mediated by H3K27 acetylation in PDAC. Moreover, we identify CSNK2A1 as a pivotal activator of autophagy, and enhanced autophagy drives gemcitabine resistance. Silmitasertib, an established CSNK2A1 inhibitor, can effectively inhibit autophagy. Notably, the combinatorial treatment of Silmitasertib with gemcitabine demonstrates remarkable efficacy in treating PDAC. In summary, our study reveals CSNK2A1 as a potent predictive factor for gemcitabine resistance in PDAC. Moreover, targeted CSNK2A1 inhibition by Silmitasertib represents a promising therapeutic strategy to restore gemcitabine sensitivity in PDAC, offering hope for improved clinical outcomes.