Testing and Validation of a Custom Retrained Large Language Model for the Supportive Care of HN Patients with External Knowledge Base.

PURPOSE: This study aimed to develop a retrained large language model (LLM) tailored to the needs of HN cancer patients treated with radiotherapy, with emphasis on symptom management and survivorship care. METHODS: A comprehensive external database was curated for training ChatGPT-4, integrating expert-identified consensus guidelines on supportive care for HN patients and correspondences from physicians and nurses within our institution's electronic medical records for 90 HN patients. The performance of our model was evaluated using 20 patient post-treatment inquiries that were then assessed by three Board certified radiation oncologists (RadOncs). The rating of the model was assessed on a scale of 1 (strongly disagree) to 5 (strongly agree) based on accuracy, clarity of response, completeness s, and relevance. RESULTS: The average scores for the 20 tested questions were 4.25 for accuracy, 4.35 for clarity, 4.22 for completeness, and 4.32 for relevance, on a 5-point scale. Overall, 91.67% (220 out of 240) of assessments received scores of 3 or higher, and 83.33% (200 out of 240) received scores of 4 or higher. CONCLUSION: The custom-trained model demonstrates high accuracy in providing support to HN patients offering evidence-based information and guidance on their symptom management and survivorship care.

Investigation on the proton range uncertainty with spectral CT-based virtual monoenergetic images.

OBJECTIVE: The stopping power ratio (SPR) prediction error will contribute to the range uncertainty of proton therapy. Spectral CT is promising in reducing the uncertainty in SPR estimation. The purpose of this research is to determine the optimal energy pairs of SPR prediction for each tissue and to evaluate the dose distribution and range difference between the spectral CT with the optimal energy pairs method and the single energy CT (SECT) method. METHODS: A new method was proposed based on image segmentation to calculate the proton dose with spectral CT images for the head and body phantom. CT number of each organ region were converted to SPR with the optimal energy pairs of each organ. The CT images were segmented into different organ parts with thresholding method. Virtual monoenergetic (VM) images from 70 keV to 140 keV were investigated to determine the optimal energy pairs for each organ based on Gammex 1467 phantom. The beam data of Shanghai Advanced Proton Therapy facility (SAPT) was employed in matRad (an open-source software for radiation treatment planning) for the dose calculation. RESULTS: The optimal energy pairs were obtained for each tissue. The dose distribution of two tumor sites (brain and lung) were calculated with the aforementioned optimal energy pairs. The maximum dose deviation between spectral CT and SECT at the target region was 2.57% and 0.84% for the lung tumor and brain tumor respectively. The range difference between spectral and SECT was significant with 1.8411 mm for the lung tumor. γ passing rate was 85.95% and 95.49% for the lung tumor and brain tumor with the criterion 2%/2 mm. CONCLUSIONS: This work presents a way to determine the optimal energy pairs for each organ and to calculate the dose distribution based on the more accurate SPR prediction.

End-to-End QA with Polymer Gel Dosimeter for Photon Beam Radiation Therapy.

With the complexity and high demands on quality assurance (QA) of photon beam radiation therapy, end-to-end (E2E) QA is necessary to validate the entire treatment workflow from pre-treatment imaging to beam delivery. A polymer gel dosimeter is a promising tool for three-dimensional (3D) dose distribution measurement. The purpose of this study is to design a fast "one delivery" polymethyl methacrylate (PMMA) phantom with a polymer gel dosimeter for the E2E QA test of the photon beam. The one delivery phantom is composed of ten calibration cuvettes for the calibration curve measurement, two 10 cm gel dosimeter inserts for the dose distribution measurement, and three 5.5 cm gel dosimeters for the square field measurement. The one delivery phantom holder is comparable in size and shape to that of a human thorax and abdomen. In addition, an anthropomorphic head phantom was employed to measure the patient-specific dose distribution of a VMAT plan. The E2E dosimetry was verified by undertaking the whole RT procedure (immobilization, CT simulation, treatment planning, phantom set-up, imaged-guided registration, and beam delivery). The calibration curve, field size, and patient-specific dose were measured with a polymer gel dosimeter. The positioning error can be mitigated with the one-delivery PMMA phantom holder. The delivered dose measured with a polymer gel dosimeter was compared with the planned dose. The gamma passing rate is 86.64% with the MAGAT-f gel dosimeter. The results ascertain the feasibility of the one delivery phantom with a polymer gel dosimeter for a photon beam in E2E QA. The QA time can be reduced with the designed one delivery phantom.

Dynamic Microbial Shifts and Signatures of Long-Term Remission in Allergic Rhinitis After an Herbal Formula Treatment.

A mixed Chinese herbal formula, Xiao-Qing-Long-Decoction (XQLD), may contribute to sustained remission in allergic rhinitis (AR), but it is unknown which factors determine such long-term effect. Here, we aimed to identify bacterial signatures associated with sustained remission. To this end, samples from AR patients at four different times were analyzed to compare the dynamic bacterial community and structure shifts. Diversity indices Chao1 showed significant difference across different time (p<0.05), and the Kruskal-Wallis test identified that Dialister (OTU_31), Roseburia (OTU_36), Bacteroides (OTU_22), Bacteroides (OTU_2040), and Prevotella_9 (OTU_5) were the significant differential bacterial taxa (p<0.05). These distinctive genera were significantly associated with the change of AR clinical indices and the predicted functional pathways such as PPAR signaling pathway, peroxisome, and citrate cycle (TCA cycle) (p<0.05), indicating that they may be important bacterial signatures involving in the sustained remission in AR (p<0.05). Besides, lower Firmicutes/Bacteroidetes (F/B) ratio at 6 months follow-up may also contribute to the long-term remission of AR. No seriously adverse events and safety concerns were observed in this study. In conclusion, XQLD is a meaningful, long-term efficient and safe medication for AR treatment. The underlying mechanisms of sustained remission in AR after XQLD treatment may be associated with the dynamic alteration of featured gut bacteria taxa.

Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies.

Intestinal barrier dysfunction contributes to the development of intestinal diseases. Propionic acid (PA), a metabolite generated by anaerobic fermentation of dietary fiber in the intestinal cavity, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role of PA in LPS-induced intestinal barrier dysfunction is still unclear. Accordingly, we examined the latent mechanism of PA and its protective role in LPS-induced intestinal barrier dysfunction by both in vitro and in vivo experiments. In vitro, we identified that PA treatment could strongly promote cell migration, inhibit activation of NLRP3 inflammasome and maintain intestinal barrier function in LPS-induced IEC-6 cells, indicating the protective effect on the intestinal barrier function of PA. Further investigation of the mechanism involved revealed that PA could suppress the activation of TLR4/NF-κB pathway. In vivo, in a LPS-induced rat model, PA-induced protective effects in intestinal barrier dysfunction could be detected. In summary, our findings clarify the role of PA in intestinal barrier dysfunction and suggest that it is promising for the treatment of LPS-related intestinal diseases.

Correction to: Gut microbial characteristics of adult patients with allergy rhinitis.

An amendment to this paper has been published and can be accessed via the original article.

Gut microbial characteristics of adult patients with allergy rhinitis.

BACKGROUND: Although recent studies have indicated that intestinal microbiota dweller are involved in the pathogenesis of allergy rhinitis (AR), the influence of gut microbiota on AR adult has not been fully elucidated yet. Hence, we carried out this study to uncover the distinctive bacterial taxa that differentiate allergy rhinitis patients from healthy individuals. Feces samples from thirty three AR patients and thirty one healthy individuals were analyzed by 16S rRNA gene sequencing. RESULTS: Results showed that the bacterial diversity in AR group was significantly higher than that of the non-AR group. Bacterial communities between AR and non-AR group were significantly differentiated as revealed by Principal coordinates analysis (PCoA) and the variation within non-AR were higher than that of the counterpart. Firmicutes, Fusobacteria, Actinobacteria, Cyanobacteria and Chloroflexi were the significantly differed phyla taxa and the top significantly distinguished bacterial genus included Prevotella_9, Phascolarctobacterium, Roseburia, Megamonas, Alistipes, Lachnoclostridium and Fusobacterium. The higher network complexity in AR group were dominated by taxa belonging to Firmicutes. The predicted function, alpha linolenic acid metabolism and bacterial invasion of epithelial cells pathway were higher in non-AR group while gonadotropin-releasing hormone (GnRH) signaling pathway, Fc γ-R mediated phagocytosis and endocytosis were higher in AR patients. Although the bacterial diversity between moderate and severe AR patients showed no significant difference, the significant correlation between featured genus and total nasal symptom score or rhinoconjunctivitis quality of life questionnaire, such as Butyricicoccus and Eisenbergiella, revealed the potential to intervene the AR status by means of gut microbiota. CONCLUSIONS: In conclusion, patients with allergy rhinitis had distinguished gut microbiota characteritics in comparison with healthy controls. The results suggest that gut microbiota might play crucial roles in influencing the course and different symptoms of AR. Trial registration ChiCTR, ChiCTR1900028613. Registered 29 December 2019, https://www.chictr.org.cn/showproj.aspx?proj=47650 .

Spatial Uniformity Assessment of Particles Distributed in a Spherical Fuel Element Using a Non-Destructive Approach.

In many manufacturing procedures, a large number of identical particles need to be disseminated uniformly into a given space. The uniformity of the spatial distribution of the particles can be critical to the properties of the final products. We proposed an image processing-based non-destructive technique to evaluate the particles' spatial uniformity in a spherical space imaged with computed tomography. Both graphic (qualitative) and numerical (quantitative) methods were developed to demonstrate the (non-) uniformity of the particles. Simulation results indicated that the technique helped detecting the non-uniformity in the particles' spatial distribution accurately. We conclude that the proposed technique can be used to test whether a number of particles in a sphere are uniformly distributed statistically and graphically.

Difference of Liver and Kidney Metabolic Profiling in Chronic Atrophic Gastritis Rats between Acupuncture and Moxibustion Treatment.

Acupuncture and moxibustion proved to be very effective in chronic atrophic gastritis (CAG). According to the Chinese traditional medicine theory, chronic diseases have an influence on the function of liver and kidney. However, there is little research to demonstrate this theory. This study is aimed at assessing the 1H NMR-based metabolic profiling in liver and kidney of CAG rats and comparing the difference between electroacupuncture and moxibustion treatment. Male SD rats were subjected to CAG modeling by intragastric administration of mixture of 2% sodium salicylate and 30% alcohol coupled with compulsive sporting and irregular fasting for 12 weeks and then treated by electroacupuncture or moxibustion at Liangmen (ST 21) and Zusanli (ST 36) acupoints for 2 weeks. A 1H NMR analysis of liver and kidney samples along with histopathological examination and molecular biological assay was employed to assess and compare the therapeutic effects of electroacupuncture and moxibustion. CAG brought characterization of metabolomic signatures in liver and kidney of rats. Both electroacupuncture and moxibustion treatment were found to normalize the CAG-induced changes by restoring energy metabolism, neurotransmitter metabolism, antioxidation metabolism, and other metabolism, while the moxibustion treatment reversed more metabolites related to energy metabolism in liver than electroacupuncture treatment. CAG did have influence on liver and kidney of rats. Both of these treatments had good effects on CAG by reversing the CAG-induced perturbation in liver and kidney. For regulating the energy metabolism in liver, the moxibustion played more important role than electroacupuncture treatment.

The Application of Auriculotherapy to the Treatment of Chronic Spontaneous Urticaria: A Systematic Review and Meta-analysis.

Auriculotherapy has been extensively used for chronic spontaneous urticaria in China. However, the evidence of its effectiveness and safety for the treatment of chronic spontaneous urticaria is insufficient. Hence, we conducted this study to compare auriculotherapy or auriculotherapy joint treatment with Western medicine for the cure of chronic spontaneous urticaria. This meta-analysis of seven randomized controlled trials showed that auriculotherapy or auriculotherapy joint treatment was significantly superior to Western medicine in curing clinical signs and symptoms of chronic spontaneous urticaria [odds ration (OR), 2.61; 95% confidence interval (CI), 1.54-4.43; p = 0.0004) and also better in total effect rate (OR, 3.81; 95% CI, 2.07-7.01; p＜0.0001). But, auriculotherapy or auriculotherapy joint treatment was similar to Western medicine in improving clinical signs and symptoms of chronic spontaneous urticaria (OR, 0.74; 95% CI, 0.35-1.56; p = 0.42). Auriculotherapy or auriculotherapy joint treatment was safer than Western medicine for curing chronic spontaneous urticaria (OR, 0.26; 95% CI, 0.09-0.80; p = 0.02). Auriculotherapy alone or auriculotherapy joint treatment appears to be more effective and safer than Western medicine that contains antihistamines in the treatment of chronic spontaneous urticaria. However, these findings should be interpreted with caution due to the unclear risk bias of methodological quality, and further studies with large-scale, better, and more rigorously designed protocol are necessary to prove these findings.

Knockdown of PYCR1 inhibits cell proliferation and colony formation via cell cycle arrest and apoptosis in prostate cancer.

Pyrroline-5-carboxylate reductase 1 (PYCR1) is an enzyme involved in cell metabolism, which has been shown to be up-regulated in cancers. However, the functions of PYCR1 in prostate cancers (PCa) are still largely unknown. In the present study, we found that PYCR1 was highly expressed in prostate cancer tissues and then knocked down PYCR1 in PCa cell lines (DU145, PC-3 and LNCap) via lentivirus-mediated gene delivery and analyzed its biological function. Both qRT-PCR and western blotting indicated that PYCR1 was suppressed efficiently after sh-PYCR1 infection. Further analysis indicated knockdown of PYCR1 significantly inhibited PCa cell growth and colony formation ability. The inhibition effects on growth were likely due to G2/M-phase arrest and enhanced cell apoptosis, as determined by flow cytometer analysis. At last, we verified the expression levels of cell cycle regulatory proteins, including CDK1, CDK2, CDK4 and Cyclin B1 were all downregulated and cell apoptotic-related proteins, including cleaved caspase 3 and cleaved PARP were increased in PCa cells after PYCR1 knockdown. Furthermore, PYCR1 has been shown not to be directly regulated by androgen receptor (AR) levels. These results show the functions of PYCR1 in PCa tumorigenesis for the first time and suggest that PYCR1 might be a good potential therapy approach for treating PCa.

Efficacy and safety of Yinchenwuling powder for hyperlipidemia: a systematic review and Meta-analysis.

OBJECTIVE: To assess the clinical effectiveness and adverse effects of Yinchenwuling powder (YCWLP) in the treatment of hyperlipidemia using Meta-analysis. METHODS: Seven electronic databases were searched for randomized controlled trials designed to evaluate the clinical effectiveness of YCWLP for hyperlipidemia published in any language prior to February 2015. Two reviewers independently identified articles, extracted data, assessed quality, and cross-checked the results. Revman 5.3 was used to analyze the data. RESULTS: Only five randomized controlled trials with poor methodology were included in the analysis. The five trials compared YCWLP with conventional lipid-lowering drugs. Meta-analysis indicated that YCWLP was more effective at the levels of total cholesterol and triglycerides, while increasing the level of high-density lipoprotein cholesterol without serious adverse effects. However, it was not more effective than lipid-lowering drugs in reducing low-density lipoprotein cholesterol and improving hemorheology. CONCLUSION: YCWLP appeared to improve lipid levels. However, given the high risk of bias among the trials, we could not conclude that YCWLP was beneficial to patients with hyperlipidemia. More rigorous trials are required to provide stronger evidence for the conclusion.

MYO6 knockdown inhibits the growth and induces the apoptosis of prostate cancer cells by decreasing the phosphorylation of ERK1/2 and PRAS40.

Prostate cancer is the second most frequently diagnosed cancer among males around the world. Myosin VI (MYO6), as a motor protein, has been reported to be implicated in cancer-related cell migration and cellular functions. To investigate the role of MYO6 in prostate cancer, immunohistochemical analysis was firstly applied to prostate cancer tissues and revealed that MYO6 was closely related with the Gleason score in prostate cancer. Then we used specific short hairpin RNA (shRNA) to downregulate MYO6 expression in DU145 and PC-3 cells and found that decreased MYO6 expression significantly suppressed cell proliferation, as determined by MTT and colony formation assays. Flow cytometry confirmed that the suppression of MYO6 promoted cell cycle arrest at the G2/M and sub-G1 phase in the DU145 cells. Furthermore, PathScan intracellular signaling array analysis demonstrated that the phosphorylation of ERK1/2 and PRAS40 was downregulated in the DU145 cells following MYO6 knockdown. Knockdown of MYO6 downregulated the expression of AKT3 and upregulated the expression of PARP, as confirmed by western blot analysis. These results suggest that MYO6 plays an essential role in the progression of prostate cancer and silencing of MYO6 may be a promising therapeutic approach for prostate cancer.

Chinese Herbal Medicine as an Adjunctive Therapy for Breast Cancer: A Systematic Review and Meta-Analysis.

Chinese herbal medicine (CHM) has been widely used as an adjunctive therapy for breast cancer, while its efficacy remains unexplored. The purpose of this study is to evaluate the efficacy of CHM combined with chemotherapy for breast cancer. The study results showed that CHM combined with chemotherapy significantly increased tumor response and KPS as compared to using chemotherapy alone (RR = 1.36; 95% CI = 1.24-1.48; P < 0.00001; RR = 1.38; 95% CI = 1.26-1.52; P < 0.00001, resp.). Besides, CHM as an adjunctive therapy significantly reduced the nausea and vomiting at toxicity grade of III-IV (RR = 0.37; 95% CI = 0.27-0.52; P < 0.00001). Moreover, the combined therapy significantly prevented the decline of WBC in patients under chemotherapy at toxicity grade of III-IV (RR = 0.49; 95% CI = 0.34-0.69; P < 0.00001) and prevented the decline of platelet at toxicity grade of III-IV or I-IV (RR = 0.29; 95% CI = 0.12-0.73; P = 0.008; RR = 0.77; 95% CI = 0.63-0.94; P = 0.009, resp.). This study suggests that CHM combined with chemotherapy in comparison with chemotherapy alone can significantly enhance tumor response, improve KPS, and alleviate toxicity induced by chemotherapy in breast cancer patients. However, a firm conclusion could not be reached due to the lack of high quality trials and large-scale RCTs, so further trials with higher quality and larger scale are needed.

Randomized trial of acupoints herbal patching in Sanfu Days for asthma in clinical remission stage.

BACKGROUND: Although China has a long history of using acupoints herbal patching (acupoints herbal patching means applying herbal patch on special acupoints to stimulate skin to form blisters, hyperemia, and even suppuration) in Sanfu Days (Sanfu Days are supposed to be the three hottest days in a year which is calculated by the ancient calendar) for the treatment of asthma, there is insufficient evidence to support its effectiveness and safety issues. This study investigated the efficacy and safety of acupoints herbal patching compared with placebo in participants with asthma in clinical remission stage. METHODS: We enrolled participants with asthma in clinical remission stage, above 13 years old and both genders in a randomized, double-blind and placebo-control trial at clinical center, School of Chinese Medicine, The University of Hong Kong to assess the effectiveness and safety of acupoints herbal patching, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for three times (these three times were 19 July, 29 July and 8 August 2010), and the primary outcome was pulmonary function test. Secondary outcome was self-made questionnaire which were designed based on Traditional Chinese Medicine theory and clinical experience summary. RESULTS: Three hundred and twenty three eligible participants were enrolled, they were randomly assigned to acupoints herbal patching group (n = 165), placebo control group (n = 158). There was no significant difference in primary and secondary outcome as compared with placebo group at the end of 3rd treatment and four times follow ups. But sub-analysis of secondary outcome in four times follow ups showed that acupoints herbal patching significantly reduced the proportion of participants who didn't need medical treatment when they had a small rise in asthma-related symptoms increased from 6-15 % at 1st follow up and 0-7 % at 3rd follow up (P < 0.05). It indicated that the proportion of participants who can spontaneous resolution of an asthma attack increased through acupoints herbal patching. In addition, acupoints herbal patching was significantly superior to placebo in reducing the percentage of participants who were susceptibly waken up by asthma symptoms from 27-14 %, and the percentage of participants who had the symptom of running nose and sneezing before onset from 18-8 % at 2nd follow up (P < 0.05). Improvements also occurred with treatment group, it reduced the proportion of participants who were spontaneous sweating at 3rd follow up (P < 0.05). CONCLUSIONS: There was no significant difference between acupoints herbal patching and placebo in pulmonary function test in this study. Self-made questionnaire showed that the lasting effect of acupoints herbal patching was significantly better than placebo in reducing the need for medications to control asthma and the proportion of susceptible symptoms in participants with asthma in clinical remission stage. It showed that the low quality of life caused by asthma-related symptoms was significantly improved through acupoints herbal patching in Sanfu Days. Besides, acupoints herbal patching was as safe as placebo for chronic stable asthma. TRIAL REGISTRATION NUMBER: HKUCTR-1128, Registration date 22 Jul 2010.

CHOP deficiency results in elevated lipopolysaccharide-induced inflammation and kidney injury.

C/EBP homologous protein (CHOP) is an important mediator of endoplasmic reticulum (ER) stress-induced cell and organ injury. Here we show that lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with ER stress and elevated CHOP. We postulated that CHOP(-/-) mice would be protected against LPS-induced-AKI. Unexpectedly, while Toll-like receptor 4 (TLR4) expression levels were comparable in kidneys of CHOP(-/-) and wild-type (WT) mice, CHOP(-/-) mice developed more severe AKI after LPS injection. Furthermore, the severe kidney injury in CHOP(-/-) mice was associated with an exaggerated inflammatory response. Serum TNF-α levels were more elevated in LPS-treated CHOP(-/-) mice. There was a 3.5-fold higher amount of renal neutrophil infiltrates in LPS-treated CHOP(-/-) than in WT mice. Additionally, the kidneys of LPS-treated CHOP(-/-) mice had a more prominent increase in NF-κB activation and further upregulation of proinflammatory genes, i.e., c-x-c motif ligand 1 (CXCL-1), macrophage inflammatory protein-2 (MIP-2), and IL-6. Finally, proximal tubules, glomeruli, and podocytes isolated from CHOP(-/-) mice also had an exaggerated proinflammatory response to LPS. Since LPS directly increased CHOP in glomeruli and podocytes of WT mice, together these data suggest that the LPS-induced increase of CHOP in kidneys may inhibit inflammatory response in renal cells and provide protection against AKI.

Protective effect of a polysaccharide from stem of Codonopsis pilosula against renal ischemia/reperfusion injury in rats.

In this study, we purified a homogeneous polysaccharide (S-CPPA1) with a molecular weight (Mw) of 133.2 kDa from the stem of Codonopsis pilosula for the first time. Gas chromatography (GC) analysis identified that S-CPPA1 contained glucose, galactose, and arabinose with a molar ratio of 10.5:3.4:1.7, along with a trace of mannose. Methylation analysis suggested S-CPPA1 was a branched polysaccharide, with five glucosidic linkage forms, namely (1→4)-linked Glcp (residue A), (1→6)-linked Galp (residue B), (1→2,6)-linked Glcp (residue C), (1→5)-linked Araf (residue D), and non-reducing terminal (1→)-linked Glcp (residue E). The protective effect of S-CPPA1 on kidney ischemia/reperfusion (I/R) injury was also evaluated. Blood urea nitrogen (BUN), creatinine and TNF-α levels, as well as lactate dehydrogenase (LDH) and alanine transaminase (AST) activities were elevated in the I/R group as compared to the sham group. On the other hand, S-CPPA1 treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by I/R. The findings imply that S-CPPA1 plays a causal role in the protection against I/R-induced renal injury and its renoprotective effect is probably mediated by inhibiting the proinflammatory cytokine TNF-α release.