Computational insights into the structure and decomposition behaviors of 2,4,6-triamino-5-nitropyrimidine-1,3-dioxide under high pressure up to 10 GPa.

CONTEXT: Inspired by the recent successful synthesis of the energetic compound 2,4,6-triamino-5-nitropyrimidine-1,3-dioxide (ICM-102), which displayed a good balance between high energy and sensitivity, the response of the structure and decomposition behaviors of ICM-102 to high pressure was systematically investigated using first principle calculations. ICM-102 exhibited a graphite-like layer structure, with the c-axis and the a-axis mainly contributing to the distance between the molecular planes. As the pressure increased from 1 atm to 10 GPa, this distance decreased from 3.166 to 2.689 Ǻ. The hydrogen bonds had the most contribution to the non-covalent interactions within the same molecular planes, resulting in the b-axis discontinuity. However, van der Waals interactions gradually appeared between molecular planes as the pressure increased to 2.5 GPa. Based on the analysis of crystal orbitals, the distribution of π bonds and the Laplacian bond order (LBO), it was determined that the generation mechanism of H2O molecules involved the cleavage of N-Oc (coordinated oxygen atoms), followed by intermolecular hydrogen transfer reactions, and ultimately the formation of H2O molecules through competition with H atoms in the amino groups within the same molecules. More importantly, the pressure dependence of LBO values for N-Oc revealed that high pressure could inhibit the ICM-102 decomposition process due to reinforcing hydrogen bonds and van der Waals interactions. This work will deepen our understanding of the stability of ICM-102 under high pressure and provide a helpful reference for its potential detonation applications. METHODS: All simulations, including geometry optimization and vibration analysis under quasi-hydrostatic pressure, were conducted using the CP2K code. The PBE function and the Goldk-Teter-Hutter (GTH) pseudopotential with the double-ζ-with-polarization (DZVP) basis set were employed. Additionally, the semiempirical dispersion correction D3 (BJ) was used to account for the intermolecular dispersion force. The simulations were performed under periodic boundary conditions, with a finest grid level cutoff set to 400 Ry for the Γ point. The Broyden-Flecher-Goldfarb-Shanno (BFGS) optimization method was used, with tighter convergence criteria applied for the subsequent calculations of infrared spectra. Finally, the wave-function analysis, such as non-covalent interaction and LBO, was conducted using the Multiwfn and VMD packages.

Consumption of Total and Specific Alcoholic Beverages and Long-Term Risk of Gout Among Men and Women.

Importance: Previous studies on alcohol consumption and incident gout have mostly included men or combined both sexes, and the sex-specific associations between alcohol consumption and gout are poorly understood. Objective: To evaluate the consumption of total and specific alcoholic beverages in association with incident gout in men and women. Design, Setting, and Participants: This prospective cohort study included 401 128 participants in the UK Biobank aged 37 to 73 years who were free of gout at baseline (2006-2010). Participants were followed up through December 31, 2021, and data were analyzed between August 2023 and June 2024. Exposure: Questionnaire-based consumption of total alcohol and specific alcoholic beverages. Main Outcomes and Measures: The outcome was incident gout, identified using hospital records. Multivariable Cox proportional hazards regression models were used to estimate sex-specific hazard ratios (HRs) and 95% CIs of incident gout associated with alcohol consumption, with a particular consideration of reverse causation bias. Results: The main analysis included 179 828 men (mean [SD] age, 56.0 [8.2] years) and 221 300 women (mean [SD] age, 56.0 [8.0] years). Current drinkers showed a higher risk of gout than never drinkers among men (HR, 1.69; 95% CI, 1.30-2.18) but not among women (HR, 0.83; 95% CI, 0.67-1.03). Among current drinkers, higher total alcohol consumption was associated with a higher risk of gout among both sexes and more strongly among men than women (men: HR, 2.05 [95% CI, 1.84-2.30]; women: HR, 1.34 [95% CI, 1.12-1.61]). The most evident sex difference in the consumption of specific alcoholic beverages was observed for beer or cider (men: mean [SD], 4.2 [4.8] pints per week; women: mean [SD], 0.4 [1.1] pints per week). Consumption of champagne or white wine, beer or cider, and spirits each was associated with a higher risk of gout among both sexes, with beer or cider showing the strongest association per 1 pint per day (men: HR, 1.60 [95% CI, 1.53-1.67]; women: HR, 1.62 [95% CI, 1.02-2.57]). Some inverse associations between light to moderate consumption of specific alcoholic beverages and gout were eliminated after adjusting for other alcoholic beverages and excluding individuals who had reduced alcohol consumption for health reasons, self-reported poor health, or had cardiovascular disease, cancer, or kidney failure at baseline, or developed gout within the first 2 years of follow-up. Conclusions and Relevance: In this cohort study, higher consumption of several specific alcoholic beverages was associated with a higher risk of gout among both sexes. The sex-specific associations for total alcohol consumption may be associated with differences between men and women in the types of alcohol consumed.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Overall Survival of Primary Single Intracranial Atypical Meningioma with Different Surgical and Postoperative Treatment Options: Evidence from the SEER Database.

Objective: The aim of this study is to evaluate the impact of different surgical and postoperative treatment options on the long-term overall survival (OS) in patients with primary single intracranial atypical meningioma. Methods: In this retrospective study, participants were drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Inclusion criteria comprised patients who underwent either gross total resection (GTR) or subtotal resection (STR). The inverse probability weighting (IPW) method using generalized boosted models was used to achieve balance in variables across various treatment groups. Subsequent to IPW, multivariate Cox analysis and Kaplan-Meier analysis were conducted, with OS as the endpoint. Results: GTR was conducted on 1650 patients, while STR was conducted on 1109 patients. Among these, 432 patients who underwent GTR and 401 patients who underwent STR received postoperative radiotherapy (PORT). In the case of patients who were under 60 years old, PORT emerged as a significant protective factor for OS in those who underwent STR (HR 0.44; 95% CI 0.23-0.84; p = 0.013). Survival curves demonstrated that patients who underwent STR with PORT exhibited comparable OS to those who underwent GTR without PORT (p = 0.546). Conversely, for patients aged 60 years or older, PORT emerged as an independent risk factor for both GTR (HR 1.42; 95% CI 1.00-2.00; p = 0.048) and STR (HR 1.81; 95% CI 1.26-2.60; p = 0.001). Conclusion: PORT may contribute to improving OS in primary single atypical meningioma patients under 60 years old who receive STR. However, in older patients who underwent either GTR or STR, the administration of PORT may be associated with a potential risk of OS. Therefore, age should be taken into account in applying PORT therapy, and the optimal treatment strategy for PORT in patients with atypical meningiomas needs to be further explored and validated.

How is vaping promoted in an illegal market? A qualitative study of Singaporeans' social media encounters.

BACKGROUND: Although Singapore has completely banned vaping, it is heavily promoted on social media. This study explored vaping-related social media content that Singaporeans are exposed to, and how it shapes vaping-related perceptions and experiences in the context of Singapore's strict regulations. METHODS: We held 10 focus group discussions with 63 Singaporeans aged 21-40 years, with diversity by sociodemographics, smoking history, vaping history and self-reported exposure to vaping-related social media content. Participants provided screenshots of any vaping-related content they encountered on their social media. Subsequently, in focus groups, they were shown a variety of this content and asked to discuss. We coded transcripts using inductive methods. RESULTS: Participants had encountered vape advertisements from neighbouring countries featuring attractive products, flavours, celebrity endorsements and entertainment shows, which they found highly appealing. Participants encountered posts that did not overtly advertise vaping but depicted people vaping in social settings, thereby normalising vaping despite its illegal status. They perceived government campaigns to deter vaping as biased and agenda driven, calling for a more nuanced message and use of local influencers and personal stories to communicate the rationale of the vaping regulations to the public. CONCLUSION: Having a law that bans vaping may not be enough; it needs to be complemented with more comprehensive marketing restrictions on social media platforms and effective enforcement of bans on social media promotions from overseas.

[Therapeutic effect and mechanism of Jingfang Granules on acute lung injury based on intestinal flora and fecal metabolomics].

This study aims to elucidate the therapeutic effect and mechanism of Jingfang Granules on acute lung injury, and to investigate the regulatory effect of Jingfang Granules on the metabolic disorders of endogenous metabolites in feces and the homeostasis of intestinal microbiota in acute lung injury, mice were randomly divided into a sham group, a model group, and a Jingfang Granules group. After modeling, the mice were continuously administered for 6 days. Using ultra-high performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry(UHPLC-HESI-QE-Orbitrap-MS/MS) metabolomics technology and 16S rRNA high-throughput sequencing technology, changes in endogenous small molecule substances and gut microbiota in mouse intestines were determined, and potential biomarkers were identified. The results showed that Jingfang Granules can regulate 11 biomarkers, including L-glutamic acid, succinic acid, arachidonic acid, linoleic acid, linolenic acid, phenylalanine, sphingosine, 2-hydroxy-2-methyl butyric acid, pyruvate, tryptophan, and palmitic acid. Metabolic pathway analysis was conducted on these 11 biomarkers using the online software MetaboAnalyst, identifying potential major metabolic pathways. Among them, a total of 10 metabolic pathways are closely related to the treatment of acute lung injury with Jingfang Granules, including alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, citrate cycle(TCA cycle), alyoxylate and dicarboxylate metabolism, arginine and proline metabolism, linoleic acid metabolism and linolenic acid metabolism, nitrogen metabolism, D-glutamine and D-gluta-matemetabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism. The results of gut microbiota showed significant differences in bacteria, mainly including Bacteroides, Akkermansia, Lachnospiraceae＿NK4A136＿group, Lachnochlostridium, and Klebsiella. Spearman analysis confirms that Akkermansia and Lachnospiraceae＿NK4A136＿group is a significant positive correlation between the abundance of succinic acid, arachidonic acid, linolenic acid, linoleic acid, butyric acid, and pyruvate in the group; Bacteroides, Klebsiella, Lachnochlostrium are significantly positively correlated with the abundance of L-glutamic acid, phenylalanine, and sphingosine. The above results indicate that the therapeutic effect of Jingfang Granules on acute lung injury is achieved by improving the imbalance of gut microbiota in mice with acute lung injury, balancing the metabolism of alanine, biosynthesis of aminoacyl tRNA, aspartic acid, glutamate, tricarboxylic acid cycle, biosynthesis of phenylalanine, tyrosine, tryptophan, and metabolism of linoleic acid.

Intradermal acupuncture in the treatment of rheumatoid arthritis with liver and kidney deficiency syndrome - A sham-controlled, randomized, clinical trial.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is called "immortal cancer", and it affects the quality of life, disability rate and even the survival of patients. This study aimed to observe the clinical efficacy, and adverse reactions of intradermal acupuncture (IA) in the treatment of RA patients with liver and kidney deficiency syndrome. MATERIALS AND METHODS: 132 RA patients were split into an IA group and a sham IA group at a 1:1 ratio. Both groups were assessed before and after the intervention with the assessments: a traditional Chinese medicine (TCM) syndrome evaluation, the Health Assessment Questionnaire (HAQ), the Disease Activity Score 28 (DAS28) and serum C-reactive protein (CRP). RESULTS: There was a statistically significant difference in TCM syndrome evaluation, HAQ, DAS28, and CRP between both groups before and after treatment (P < 0.01). The improvement of TCM syndrome evaluation (95% CI [1.14(0.38-1.89)]; P = 0.001), HAQ (95% CI [2.00(1.00-3.00)]; P = 0.003), and DAS28 (95% CI [0.11(0.02-0.20)]; P = 0.021) in the IA group was more obvious than that in the sham IA group (P < 0.05), except for CRP (95% CI [0.50(- 2.09 to 7.08)], P = 0.786). The difference in CRP outcome changes between the two groups was not statistically significant (P > 0.05). Both groups had comparable results in the implementation of RA in the upper and lower extremity acupoints and did not differ due to different sites (IA group: P = 0.852; sham IA group: P = 0.861). The comparison of effective rate of the upper limb as well as that of the lower limb was statistically significant (P = 0.001). Besides, patients reported no adverse effects. CONCLUSION: The IA intervention was associated with a promising effect on the decrease in RA disease activity and delayed overall disease progression.

Analysis of risk factors of suicidal ideation in adolescent patients with depression and construction of prediction model.

BACKGROUND: Major depressive disorder is a common mental illness among adolescents and is the largest disease burden in this age group. Most adolescent patients with depression have suicidal ideation (SI); however, few studies have focused on the factors related to SI, and effective predictive models are lacking. AIM: To construct a risk prediction model for SI in adolescent depression and provide a reference assessment tool for prevention. METHODS: The data of 150 adolescent patients with depression at the First People's Hospital of Lianyungang from June 2020 to December 2022 were retrospectively analyzed. Based on whether or not they had SI, they were divided into a SI group (n = 91) and a non-SI group (n = 59). The general data and laboratory indices of the two groups were compared. Logistic regression was used to analyze the factors influencing SI in adolescent patients with depression, a nomogram prediction model was constructed based on the analysis results, and internal evaluation was performed. Receiver operating characteristic and calibration curves were used to evaluate the model's efficacy, and the clinical application value was evaluated using decision curve analysis (DCA). RESULTS: There were differences in trauma history, triggers, serum ferritin levels (SF), high-sensitivity C-reactive protein levels (hs-CRP), and high-density lipoprotein (HDL-C) levels between the two groups (P < 0.05). Logistic regression analysis showed that trauma history, predisposing factors, SF, hs-CRP, and HDL-C were factors influencing SI in adolescent patients with depression. The area under the curve of the nomogram prediction model was 0.831 (95%CI: 0.763-0.899), sensitivity was 0.912, and specificity was 0.678. The higher net benefit of the DCA and the average absolute error of the calibration curve were 0.043, indicating that the model had a good fit. CONCLUSION: The nomogram prediction model based on trauma history, triggers, ferritin, serum hs-CRP, and HDL-C levels can effectively predict the risk of SI in adolescent patients with depression.

Combining pathological risk factors and T, N staging to optimize the assessment for risk stratification and prognostication in low-risk stage III colon cancer.

BACKGROUND: This study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future. PATIENTS AND METHODS: PRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan-Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation. RESULTS: Nine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004-7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158-5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953-17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623-13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317-6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858-5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613-2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731-2.033, P < 0.001). CONCLUSION: Combined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.

Clinical efficacy of rhGM-CSF gel and medical collagen sponge on deep second-degree burns of infants: A randomized clinical trial.

BACKGROUND: This study aimed to observe clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel, medical collagen sponge and rhGM-CSF gel in combination with medical collagen sponge on deep second-degree burns of head, face or neck in infants. METHODS: A total of 108 infants with deep second-degree burns on head, face or neck were randomly divided into rhGM-CSF group, medical collagen sponge group, and rhGM-CSF + medical collagen sponge group. The scab dissolving time, healing time, bacterial positive rate and Vancouver scar scale were evaluated and analyzed. RESULTS: The data analysis showed that scab dissolving time and healing time were shorter in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group, and the difference was statistically significant (P < .05). Bacterial positive rate was lower in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). After 3 months, score of Vancouver scar scale (scar thickness, pliability, pigmentation and vascularity) was less in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). CONCLUSION: rhGM-CSF gel in combination with medical collagen sponge is significantly effective in treating deep second-degree burns of head, face or neck in infants. This combination is beneficial for infection control, acceleration of scab dissolving and wound healing, and reduction of scar hyperplasia and pigmentation, which is worthy of clinical application and promotion.

A study on molecular mechanism of Xihuang pill in the treatment of glioblastoma based on network pharmacology and validation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains unclear. AIM OF THE STUDY: This study aimed to explore the core molecular mechanisms of Xihuang pill in treating glioblastoma by an integrative pharmacology-based investigation. MATERIALS AND METHODS: The main active compounds of Xihuang pill were identified from TCMSP, BATMAN-TCM, TCMID and CNKI. Glioblastoma-related therapeutic targets were retrieved from GeneCards and UniProt. Subsequently, a protein-protein interaction (PPI) network analysis was constructed using STRING. GO and KEGG enrichment were performed to analyze the intersection targets between the active compounds of Xihuang pill and glioblastoma. Based on the above analysis, we built a CTP network. The in vitro and in vivo experiments were further performed to validate the crucial molecular targets of Xihuang pill for the treatment of glioblastoma. RESULTS: A total of sixty active compounds of Xihuang pill and ten potential targets related to glioblastoma were found. Based on topological analysis, fourteen ingredients were selected as the main active compounds, and MY11 might be the most important metabolite in Xihuang pill. PI3K/Akt signaling pathway and receptor tyrosine kinases were considered as crucial targets for Xihuang pill against glioblastoma through KEGG enrichment and CTP analysis. The present experiments indicated that Xihuang pill suppressed the activation of PI3K/Akt/mTOR signaling pathway in glioblastoma cells and mouse xenografts via modulating the expression of PTEN and Rheb proteins, the interaction between TSC2 and Rheb, and the production of PIP3. Meanwhile, after glioblastoma cells treatment with Xihuang pil, the release of IL-1ß, INF-γ was increased and the production of IL-10, TGF-ß1 was decreased in glioblastoma cells after incubated with Xihuang pill. In addition, the activation of the upstream positive modulators of PI3K/Akt/mTOR pathway including PDGF/PDGFR and FGF/FGFR signaling were down-regulated in glioblastoma cells and mouse xenografts after treatment with Xihuang pill. CONCLUSION: Taken together, Xihuang pill inhibiting glioblastoma cell growth might be partly through down-regulating the activation of PDGF/PDGFR or FGF/FGFR-PI3K/Akt/mTOR signaling axis and improving immuno-suppressive micro-environment of glioblastoma.

Effects of the Oat Hay Feeding Method and Compound Probiotic Supplementation on the Growth, Antioxidant Capacity, Immunity, and Rumen Bacteria Community of Dairy Calves.

This study aimed to investigate the effects of the oat hay feeding method and compound probiotics (CMP) on the growth, health, serum antioxidant and immune indicators, rumen fermentation, and bacteria community of dairy calves from 3 to 5 months of age. Forty-eight female Holstein calves (80 ± 7 days of age, 93.71 ± 5.33 kg BW) were selected and randomly divided into four groups. A 2 × 2 factorial design was adopted for the experiment, with the factors of the oat hay feeding method (fed as free-choice or 16.7% in the diet) and compound probiotics (CMP) inclusion (0.15% or 0%) in the pelleted starter. The results showed that, compared with giving oat hay as free-choice, feeding a diet of 16.7% oat hay increased the pelleted starter intake at 1-84 d (p < 0.05), with an average daily gain (ADG) at 61-84 d (p = 0.02); adding CMP to the pelleted starter did not significantly affect body weight, and reduced the fecal index (p < 0.05). Feeding 16.7% oat hay increased the concentration of IgA, IgG, and IgM (p < 0.01), while adding CMP increased the catalase (p < 0.01) and decreased the concentration of malondialdehyde (p < 0.01) in serum. Feeding 16.7% oat hay increased the ruminal concentration of propionic acid (p < 0.05) and isobutyric acid (p = 0.08), and decreased the ruminal pH (p = 0.08), the concentration of acetic acid (p < 0.05), and the ratio of acetic acid to propionic acid (p < 0.01). Feeding 16.7% oat hay reduced the relative abundance of ruminal Firmicutes, Unidentified-Bacteria, Actinobacteria, Prevotella, NK4A214-group, Olsenella, and Actinobacteriota (p < 0.05); adding CMP increased the relative abundance of ruminal Prevotella, Rikenellaceae-RC9-gut-group, Ruminococcus, NK4A214-group, and Ruminococcus (p < 0.05), and decreased the abundance of Desulfobacterora, Prevotella-7, and Erysipelotricaceae-UCG-002 (p < 0.05). In conclusion, feeding a diet of 16.7% oat hay increased the pelleted starter intake and average daily gain, while slightly reducing the ruminal pH values; adding CMP to the pelleted starter resulted in reduced diarrhea incidence, increased serum antioxidant capacity and immunity, as well as ruminal richness and diversity of microorganisms in dairy calves from 3 to 5 months of age.

[Research of implant accuracy using a digital registration method].

PURPOSE: The aim of this study was to introduce a new method to evaluate the clinical accuracy of implant position. The results were compared to traditional cone beam CT (CBCT) method. METHODS: A total of 36 implants from 24 patients with sufficient bone volume were enrolled into the study. CBCT method and digital registration method were compared to evaluate the accuracy of implant position. The measurement parameters were defined as deviations between ideal and postsurgical implant position at occlusal point(d1), apical point(d2) and axis(α). The deviations between two methods were analyzed with SPSS 19.0 software package. RESULTS: The deviations between ideal and postsurgical implant position using CBCT were (0.88±0.64) mm for occlusal point, (1.07±0.85) mm for apical point and (4.74±2.35)° for angle. In digital registration method, the deviations were (0.86±0.67) mm for occlusal point, (1.12±0.88) mm for apical point and (4.56±2.66)° for angle. No significant difference(P＞0.05) was found between the two methods. CONCLUSIONS: There was no significant difference between the two methods in evaluating the clinical accuracy of implant position. Digital registration method could be accepted in clinical application.

Xihuang pill in the treatment of cancer: TCM theories, pharmacological activities, chemical compounds and clinical applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pill as a famous traditional Chinese formula has long been used as an adjuvant therapy for cancer. AIM OF THE STUDY: This study is aimed at summarizing recent advances in research of Xihuang pill's anti-cancer efficacies from the theoretical basis of traditional Chinese medicine, pharmacological activities, chemical components and its clinical application. MATERIALS AND METHODS: The literature information was obtained from several authoritative databases including PubMed, Embase, Cochrane Library, CNKI and Wan Fang before April 30, 2023. We also analyzed the representatively chemical compounds of Xihuang pill in vivo experiments using HPLC-Q/TOF-MS. RESULTS: The present study indicated that Xihuang pill, a classic anti-tumor prescription, had efficacies of strengthening body resistance, clearing heat and detoxification, and promoting blood circulation for removing blood stasis. Modern basic researches showed that Xihuang pill played anti-cancer roles through inducing cancer cell apoptosis, inhibiting cell proliferation, migration, invasion and angiogenesis, improving immune function and tumor microenvironment, and regulating related signaling pathways. Its chemical components are primarily consisted of amino acids, terpenoids, fatty acids, fatty acid esters, phenolics, bile acids, bile pigments and volatile oil. Clinically, Xihuang pill, as an adjuvant drug for cancer treatment, was mostly combined with chemotherapy, which could prolong survival, enhance response rate, improve patients' life quality, regulate immune function and alleviate chemotherapy-induced toxicities. CONCLUSIONS: This present study suggests that Xihuang pill may be a promising adjuvant therapy for cancer, and proposes the possibility of future research directions for Xihuang pill based on the current research status.

Low-coverage and cost-effective whole-genome sequencing assay for glioma risk stratification.

PURPOSE: To investigate chromosomal instability (CIN) as a biomarker for glioma risk stratifications, with cost-effective, low-coverage whole-genome sequencing assay (WGS). METHODS: Thirty-five formalin-fixed paraffin-embedded glioma samples were collected from Huashan Hospital. DNA was sent for WGS by Illumina X10 at low (median) genome coverage of 1.86x (range: 1.03-3.17×), followed by copy number analyses, using a customized bioinformatics workflow-Ultrasensitive Copy number Aberration Detector. RESULTS: Among the 35 glioma patients, 12 were grade IV, 10 grade III, 11 grade II, and 2 Grade I cases, with high chromosomal instability (CIN +) in 24 (68.6%) of the glioma patients. The other 11 (31.4%) had lower chromosomal instability (CIN-). CIN significantly correlates with overall survival (P = 0.00029). Patients with CIN + /7p11.2 + (12 grade IV and 3 grade III) had the worst survival ratio (hazard ratio:16.2, 95% CI:6.3-41.6) with a median overall survival of 24 months. Ten (66.7%) patients died during the first two follow-up years. In the CIN + patients without 7p11.2 + (6 grade III, 3 grade II), 3 (33.3%) patients died during follow-up, and the estimated overall survival was around 65 months. No deaths were reported in the 11 CIN- patients (2 grade I, 8 grade II, 1 grade III) during the 80-month follow-up period. In this study, chromosomal instability served as a prognosis factor for gliomas independent of tumor grades. CONCLUSION: It is feasible to use cost-effective, low-coverage WGS for risk stratification of glioma. Elevated chromosomal instability is associated with poor prognosis.

Projection of Premature Cancer Mortality in Hunan, China, Through 2030: Modeling Study.

BACKGROUND: The United Nations Sustainable Development Goals for 2030 include reducing premature mortality from noncommunicable diseases by one-third. Although previous modeling studies have predicted premature mortality from noncommunicable diseases, the predictions for cancer and its subcategories are less well understood in China. OBJECTIVE: The aim of this study was to project premature cancer mortality of 10 leading cancers in Hunan Province, China, based on various scenarios of risk factor control so as to establish the priority for future interventions. METHODS: We used data collected between 2009 and 2017 from the Hunan cancer registry annual report as empirical data for projections. The population-attributable fraction was used to disaggregate cancer deaths into parts attributable and unattributable to 10 risk factors: smoking, alcohol use, high BMI, diabetes, physical inactivity, low vegetable and fruit intake, high red meat intake, high salt intake, and high ambient fine particulate matter (PM2.5) levels. The unattributable deaths and the risk factors in the baseline scenario were projected using the proportional change model, assuming constant annual change rates through 2030. The comparative risk assessment theory was used in simulated scenarios to reflect how premature mortality would be affected if the targets for risk factor control were achieved by 2030. RESULTS: The cancer burden in Hunan significantly increased during 2009-2017. If current trends for each risk factor continued to 2030, the total premature deaths from cancers in 2030 would increase to 97,787 in Hunan Province, and the premature mortality (9.74%) would be 44.47% higher than that in 2013 (6.74%). In the combined scenario where all risk factor control targets were achieved, 14.41% of premature cancer mortality among those aged 30-70 years would be avoided compared with the business-as-usual scenario in 2030. Reductions in the prevalence of diabetes, high BMI, ambient PM2.5 levels, and insufficient fruit intake played relatively important roles in decreasing cancer premature mortality. However, the one-third reduction goal would not be achieved for most cancers except gastric cancer. CONCLUSIONS: Existing targets on cancer-related risk factors may have important roles in cancer prevention and control. However, they are not sufficient to achieve the one-third reduction goal in premature cancer mortality in Hunan Province. More aggressive risk control targets should be adopted based on local conditions.

Chrysanthemum sporopollenin: A novel vaccine delivery system for nasal mucosal immunity.

Objective: Mucosal immunization was an effective defender against pathogens. Nasal vaccines could activate both systemic and mucosal immunity to trigger protective immune responses. However, due to the weak immunogenicity of nasal vaccines and the lack of appropriate antigen carriers, very few nasal vaccines have been clinically approved for human use, which was a major barrier to the development of nasal vaccines. Plant-derived adjuvants are promising candidates for vaccine delivery systems due to their relatively safe immunogenic properties. In particular, the distinctive structure of pollen was beneficial to the stability and retention of antigen in the nasal mucosa. Methods: Herein, a novel wild-type chrysanthemum sporopollenin vaccine delivery system loaded with a w/o/w emulsion containing squalane and protein antigen was fabricated. The unique internal cavities and the rigid external walls within the sporopollenin skeleton construction could preserve and stabilize the inner proteins. The external morphological characteristics were suitable for nasal mucosal administration with high adhesion and retention. Results: Secretory IgA antibodies in the nasal mucosa can be induced by the w/o/w emulsion with the chrysanthemum sporopollenin vaccine delivery system. Moreover, the nasal adjuvants produce a stronger humoral response (IgA and IgG) compared to squalene emulsion adjuvant. Mucosal adjuvant benefited primarily from prolongation of antigens in the nasal cavity, improvement of antigen penetration in the submucosa and promotion of CD8+ T cells in spleen. Disccusion: Based on effective delivering both the adjuvant and the antigen, the increase of protein antigen stability and the realization of mucosal retention, the chrysanthemum sporopollenin vaccine delivery system has the potential to be a promising adjuvant platform. This work provide a novel idea for the fabrication of protein-mucosal delivery vaccine.

Construction and Validation of a Novel Prognosis Model in Colon Cancer Based on Cuproptosis-Related Long Non-Coding RNAs.

Colon cancer (CC) is one of the most common (6%) malignancies and leading cause of cancer-associated death (more than 0.5 million) worldwide, which demands reliable prognostic biomarkers. Cuproptosis is a novel modality of regulated cell death triggered by the accumulation of intracellular copper. LncRNAs have been reported as prognostic signatures in different types of tumors. However, the correlation between cuproptosis-related lncRNAs (CRLs) and CC remains unclear. Data of CC patients were downloaded from public databases. The prognosis-associated CRLs were identified by co-expression analysis and univariate Cox. Least absolute shrinkage and selection operator were utilized to construct the CRLs-based prognostic signature in silico for CC patients. CRLs level was validated in human CC cell lines and patient tissues. ROC curve and Kaplan-Meier curve results revealed that high CRLs-risk score was associated with poor prognosis in CC patients. Moreover, the nomogram revealed that this model possessed a steady prognostic prediction capability with C-index as 0.68. More importantly, CC patients with high CRLs-risk score were more sensitive to eight targeted therapy drugs. The prognostic prediction power of the CRLs-risk score was further confirmed by cell lines, tissues and two independent CC cohorts. This study constructed a novel ten-CRLs-based prognosis model for CC patients. The CRLs-risk score is expected to serve as a promising prognostic biomarker and predict targeted therapy response in CC patients.

Guggulsterone from Commiphora mukul potentiates anti-glioblastoma efficacy of temozolomide in vitro and in vivo via down-regulating EGFR/PI3K/Akt signaling and NF-κB activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Myrrh is an aromatic oleo-gum resin extracted from the stem of Commiphora myrrha (Nees) Engl., and has the efficacies to promote blood circulation and remove blood stasis. Myrrh is mainly used for the treatment of chronic diseases including cancer. Guggulsterone, a major active steroid extracted from myrrh, has been found to inhibit cancer cell growth. Glioblastoma is the most common malignancy of central nervous system, and its prognosis remains very poor mainly due to chemotherapeutic resistance. The active status of EGFR/PI3K/Akt and NF-κB signaling in glioblastoma contributed to poor response for chemotherapy, and blocking this signaling with antagonists sensitized glioblastoma cells to chemotherapy. AIM OF THE STUDY: The present study will investigate whether guggulsterone potentiates the anti-glioblastoma efficacy of temozolomide by down-regulating EGFR/PI3K/Akt signaling and NF-κB activation. MATERIALS AND METHODS: Cell viability and proliferation was determined by cell counting Kit-8 and colony formation assays. Cell apoptosis was evaluated by Annexin V/PI and hoechst 33342 staining assays. Molecular techniques such as western blotting and real-time quantitative PCR were used to demonstrate guggulsterone in vitro effect on EGFR/PI3K/Akt signaling and NF-κB activation. Finally, in vivo studies were performed in orthotopic mouse models of glioblastoma. RESULTS: The results demonstrated that guggulsterone enhanced temozolomide-induced growth inhibition and apoptosis in human glioblastoma U251 and U87 cells. Furthermore, the synergistic anti-glioblastoma efficacy between guggulsterone and temozolomide was intimately associated with the inhibition of EGFR/PI3K/Akt signaling and NF-κB activation in U251 and U87 cells. Our in vivo results on orthotopic xenograft models similarly indicated that guggulsterone potentiated temozolomide-induced tumor growth inhibition through suppressing EGFR/PI3K/Akt signaling pathway and NF-кB activity. CONCLUSIONS: The present study suggested that guggulsterone potentiated anti-glioblastoma efficacy of temozolomide through down-regulating EGFR/PI3K/Akt signaling pathway and NF-кB activation.

[Accuracy evaluation of static guided implant placement using an intraoral scan method].

PURPOSE: To evaluate the accuracy of static guided implant placement with intraoral scanning technology and to analyze the influencing factors of guided surgery. METHODS: Totally 27 cases were included in this retrospective study. The implant designs were made in 3Shape Implant Studio and then guided implant surgeries were performed with CAD-CAM templates. Postoperative implant positions were detected with an intraoral scanner (3Shape TRIOS) and deviation of implantation was evaluated using established CAD/CAM based evaluation method. SAS 9.4 software package was used for data analysis. RESULTS: The mean deviation of entrance point and apical point was (1.182±0.609) mm and (1.658±0.741) mm, respectively. Angular deviation was (5.712±3.347)°. Implant quadrant, location of the implant site, guidance degree, supporting type and implant size influenced direction deviation, while angular deviation was mainly affected by guidance degree and number of missing teeth. CONCLUSIONS: Accuracy of static guided implant placement can be influenced by many factors. More research is needed to improve the accuracy of static guided implantation.