The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective To compare the difference and consistency between OPD-Scan Ⅲ and IOL-Master 700 in the measurement of corneal curvature(flat keratometry,K1 and steep keratometry,K2)and horizontal corneal diameter(white-to-white(WTW)distance).Methods Totally 268 patients with 328 eyes(164 right eyes and 164 left eyes)who underwent cataract surgery at the Department of Ophthalmology of the Aerospace Centre Hospital from October 2021 to September 2022 were selected for this study.The K1,K2,and WTW values of the sampled right or left eyes were measured and analyzed using OPD-Scan Ⅲ and IOL-Master 700,respectively.Parameter comparisons were performed through paired t-tests;correlations between parameters were detected through the Pearson correlation analysis;and the Bland-Altman method and intragroup correlation coefficient(ICC)analysis were employed to determine the consistency of parameter measurements between the two instruments.Results The K1 and K2 values measured by OPD-Scan Ⅲ were greater than those measured by IOL-Master 700,while the WTW values were lower than those measured by IOL-Master 700,but the differences were statistically significant(all P＜0.001).K1,K2,and WTW values measured by OPD-Scan Ⅲ were positive-ly correlated with the corresponding values measured by IOL-Master 700,and the differences were statistically significant(all P＜0.001).The proportions of K1,K2,and WTW values outside the 95％limits of agreement for both instruments were within 5％,but the absolute value of the difference in values within the 95％limits of agreement was close to or more than(1.0)D,indicating a sizeable clinical deviation.ICC analysis confirmed a good consistency between K1 and K2 values of the left and right eyes measured by the two instruments(ICC＞0.90).The difference in WTW values measured by the two instruments was significantly correlated with K2 values(both P＜0.05).There were 5 samples(83.33％)outside the positive deviation range of WTW values,of which K2 measured by IOL-Master 700 was above 47.03.Conclusion The OPD-Scan Ⅲ and IOL-Master 700 have been found to have measurement biases when assessing K1,K2 and WTW.In clini-cal practice,the two instruments cannot be interchanged as an alternative to each other.The WTW values measured by IOL-Master 700 are greater than those obtained by OPD-Scan Ⅲ;when K2≥47.03,the WTW values may not be reliably ref-errable.

Aim To explore the possibility of resveratrol ( RES) combined with irinotecan ( IRI) in the treatment of colorectal cancer ( CRC ) and the underlying molecular mechanism of RES ameliorating IRI chemoresistance of CRC cells. Methods CRC cells used in this study were HT-29 and RKO cells. The effects of RES, IRI and their combination on the proliferation of CRC cells were analyzed by MTT assay and colony formation assay. The effects of RES,IRI and their combination on the migration of CRC cells were assessed by Wound-healing assay. On this basis,the role of RES in regulating IRI chemoresistance of CRC cells and the underlying molecular mechanisms were further explored. Results The proliferation and migration ability of CRC cells in the RES and IRI combined treatment group were significantly lower than those in the IRI treated group, which showed that RES could enhance the inhibiting effect of IRI on the proliferation and migration of CRC cells, indicating that RES was able to a-meliorate the chemoresistance of CRC cells to IRI. And remarkably lower marker proteins expression levels of EGFR/AKT/mTOR signaling pathway in the RES and IRI combined treatment group was observed. Moreover, both EGFR activator (NSC 228155) and AKT activator (SC79) could reverse the ameliorating effect of RES on IRI chemoresistance of CRC cells, whereas AKT inhibitor (MK2206 ) could partially reverse the effect of NSC 228155. Conclusions RES can inhibit the proliferation and migration of CRC cells by down-regulating EGFR/AKT/mTOR signaling pathway, so as to ameliorate the chemoresistance of CRC cells to IRI, suggesting that RES combined with IRI can be a promising novel treatment for CRC.

[Abstract] Objective To explore the inhibitory effect of sodium ferulate (SF) on the inflammatory response in migraine rats by regulating the c-Jun N-terminal kinase (JNK) / p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Methods The migraine rat model was prepared by intraperitoneal injection of nitroglycerin. After successful modeling, the rats were randomly grouped into model group, SF low dose (SF-L) group (50 mg/ kg), SF high dose (SF-H) group (100 mg/ kg), SF+JNK inhibitor (SF + SP600125) group (SF 100 mg/ kg +SP600125 10 mg/ kg), and SF+JNK activator [SF + anisomycin(AN)] group (SF 100 mg/ kg +AN 5 mg/ kg), 12 in each group, another 12 SD rats without treatment were taken as blank group. The behavioral changes of the rats in each group were observed 24 hours after the administration, the levels of 5-hydroxytryptamine (5-HT), nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum were detected by ELISA, the neuronal apoptosis in brain tissue was observed by TUNEL staining, immunohistochemistry was used to evaluate the expressions of TNF-α, IL-6 and calcitonin gene-related peptide (CGRP) in brain tissue, Western blotting was used to detect the expressions of JNK/ p38 MAPK pathway-related proteins in brain tissue. Results Compared with the blank group, the number of times of scratching the head and climbing the cage of the rats in the model group increased significantly, and the apoptosis rate of neurons increased significantly; the content of 5-HT in serum decreased significantly, and the levels of NO, TNF-α and IL-6 increased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of phosphorylated JNK (p-JNK) / JNK and phosphorylated p38 MAPK(p-p38 MAPK) / p38 MAPK in brain tissue obviously increased (all P<0. 05). Compared with the model group, the number of times of scratching the head and the times of climbing the cage of the rats in the SF-L group and the SF-H group reduced significantly, and the neuron apoptosis rate reduced significantly; the content of 5-HT in serum increased significantly, and the levels of NO, TNF-α and IL-6 decreased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of p-JNK/ JNK and p-p38 MAPK/ p38 MAPK in brain tissue obviously decreased (all P<0. 05). Compared with SF-H group, the protective effect of SF on migraine rats in SF+SP600125 group enhanced significantly; the protective effect of SF on migraine rats in the SF+AN group reversed significantly. Conclusion SF may inhibit the expression of JNK/ p38 MAPK signaling pathway, effectively inhibit neurogenic inflammatory response in migraine rats, reduce neuronal apoptosis, and achieve a protective effect on migraine rats.

Ischemic stroke causes brain inflammation and multi-organ injury, which is closely associated with the peroxisome proliferator-activated receptor-gamma (PPARγ) signaling pathway. Recent studies have indicated that ginsenoside Rb1 (GRb1) can protect the integrity of the blood-brain barrier after stroke. In the current study, a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established to determine whether GRb1 can ameliorate brain/lung/intestinal barrier damage via the PPARγ signaling pathway. Staining (2,3,5-triphenyltetrazolium chloride, hematoxylin, and eosin) and Doppler ultrasonography were employed to detect pathological changes. Endothelial breakdown was investigated with the leakage of Evans Blue dye and the expression of TJs (tight junctions) and AJs (adherent junctions). Western blot and immunofluorescence were used to determine the levels of cell junction proteins, PPARγ and NF-κB. Results showed that GRb1 significantly mitigated multi-organ injury and increased the expression of cerebral microvascular, pulmonary vascular, and intestinal epithelial connexins. In brain, lung, and intestinal tissues, GRb1 activated PPARγ, decreased the levels of phospho-NF-κB p65, and inhibited the production of proinflammatory cytokines, thereby maintaining barrier permeability. However, co-treatment with GRb1 and the PPARγ antagonist GW9662 reversed the barrier-protective effect of GRb1. These findings indicated that GRb1 can improve stroke-induced brain/lung/intestinal barrier damagevia the PPARγ pathway.
Animals ; Brain ; Brain Ischemia ; Ginsenosides ; Infarction, Middle Cerebral Artery ; Lung ; Mice ; NF-kappa B ; Neuroprotective Agents ; PPAR gamma ; Reperfusion ; Reperfusion Injury ; Signal Transduction

ObjectiveTo investigate the effect of combined therapy of lung and intestine （Mahuangtang + Da Chengqitang） on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in rats and its protective mechanism. MethodWistar rats were randomly divided into blank group， model group， low-， medium-， and high-dose groups with combined therapy of lung and intestine ， and dexamethasone group. LPS （10 mg·kg^-1） was given （ip） to induce ALI in rats. The general state of rats in each group was observed and recorded. The body temperature of rats in each group was recorded 0-8 h after modeling by means of anal temperature measurement. Serum and lung tissues were collected 24 h after modeling. Serum levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and arginase-1 （Arg-1） were determined by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein levels of nuclear factor kappa B p65 （NF-κB p65）， phosphorylated NF-κB p65 （p-NF-κB p65）， NF-κB inhibitor α （IκBα）， and phosphorylated IκBα （p-IκBα） in lung tissues of rats. The levels of classically activated （M1） macrophage marker CD80 and IL-1β and macrophage markers F4/80 and IL-10 were detected by double immunofluorescence. ResultCompared with the blank group， the model group showed increased body temperature and thermal response index （TRI）， elevated serum levels of pro-inflammatory factor TNF-α and IL-1β and anti-inflammatory factor IL-10 （P<0.01）， up-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues （P<0.01）， and increased levels of F4/80， CD80， and IL-1β in lung tissues （P<0.01）. Compared with the model group， the lung-intestine combined treatment groups and the dexamethasone group exhibited decreased body temperature and TRI in rats （P<0.01）， declined serum levels of inflammatory factor TNF-α and IL-1β （P<0.05， P<0.01）， elevated serum levels of anti-inflammatory factor IL-10 and Arg-1 （P<0.05， P<0.01）， down-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues （P<0.05， P<0.01）， decreased levels of CD80 and IL-1β， and increased levels of IL-10 in lung tissues （P<0.01）， while the level of F4/80 was not significantly changed. ConclusionThe combined therapy of lung and intestine can obviously alleviate the fever and inflammatory state of ALI rats， and the mechanism may be related to the inhibition of NF-κB inflammatory pathway and the polarization of lung tissue macrophages to anti-inflammatory phenotype.

Lung and intestine combination therapy(LICT) is effective in the treatment of acute lung injury(ALI). In this study, the combination of Mahuang Decoction and Dachengqi Decoction(hereinafter referred to as the combination), a manifestation of LICT, was employed to explore the effect of nuclear factor kappaB(NF-κB)/nucleotide binding oligomerization domain-like receptors-3(NLRP3) pathway and alveolar macrophage activation on the lung inflammation in rats with ALI, for the purpose of elucidating the mechanism of LICT in treating ALI. After the modeling of ALI with limpolysaccharide(LPS, ip), rats were respectively given(ig) the combination at 10, 7.5, and 5 g·kg~(-1)(high-dose, medium-dose, and low-dose LICT groups, separately), once every 8 h for 3 times. Haematoxylin-eosin(HE) staining was used to observe the histopathological changes of lung tissue, followed by the scoring of inflammation. Immunohistochemistry was applied to detect alveolar macrophage activation, enzyme-linked immunosorbent assay(ELISA) was applied to detect the serum content of tumor necrosis factor-α(TNF-α) and interleukin-18(IL-18), Western blot was applied to detect the protein expression of phosphorylated-nuclear factor kappaB p65(p-NF-κB p65), nuclear factor kappaB p65(NF-κB p65), phosphorylated-inhibitor kappaB alpha(p-IκBα), inhibitor kappaB alpha(IκBα), and NLRP3 in lung tissue, and quantitative reverse transcription-PCR(qRT-PCR) was applied to detect the mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. The results showed that LICT groups demonstrated lung injury relief, decrease in inflammation score, alleviation of alveolar macrophage activation, significant decline in serum content of inflammatory factors TNF-α and IL-18, and decrease of the protein expression of p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3, and mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. In summary, LICT has definite therapeutic effect on ALI. The mechanism is that it inhibits alveolar macrophage activation by suppressing NF-κB/NLRP3 signaling pathway, thereby reducing the activation and release of inflammatory factors and finally inhibiting inflammation.
Acute Lung Injury/genetics* ; Animals ; Drugs, Chinese Herbal ; Intestines ; Lipopolysaccharides ; Lung/metabolism* ; Macrophage Activation ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Rats ; Signal Transduction

Background Women face more reproductive health problems in their whole life cycle. Occupational exposure to harmful factors in the petrochemical industry may have a synergistic effect on women’s existing health problems. Objective To analyze the influencing factors of perimenopausal syndrome (PMS) in female workers in petrochemical industry, and establish a nomogram model of the risk of PMS in female workers, so as to provide a easy and quick health monitoring and evaluation method for female workers. Methods A total of 2653 perimenopausal female workers aged 45-55 years old were selected from a petrochemical enterprise. A questionnaire survey was conducted to collect information on demographic characteristics, occupational characteristics, psychological status, and reproductive health information. The prevalence of PMS of female workers was evaluated by the Kupperman Index Scale, the physical fatigue and mental fatigue were evaluated by the Fatigue Scale. A linear graph prediction model was established by multiple logistic regression. A nomogram was presented and C-index was used to verify the differentiation of the model. Then Bootstrap method was used for internal validation. Results Among the 2653 female worker, a total of 1306 cases (49.2%) presented PMS with a Kupperman score ≥7. The main symptoms were fatigue (79.95%), irritability (71.32%), and insomnia (66.79%). Significant differences in PMS prevalence were found among female workers of different age, body mass index, and working posture groups (P < 0.05). The participants with alcohol drinking, maternal premature or late menopause, hypertension, lack of physical exercise, heavy lifting, sick leave in the last 6 months, combined occupational exposures to dust, chemicals, noise [> 80 dB(A)], or electromagnetic field, and not wearing protective masks, gloves or protective earplugs reported higher prevalence rates of PMS (P < 0.05). The prevalence rate of PMS in female workers with sleep duration ≤ 6 h was higher than that with > 6 h (P < 0.05), and higher in female workers with physical and mental fatigue than in those without (P < 0.05). The results of logistic regression analysis showed that those with maternal premature or late menopause (OR=1.572, 95%CI: 1.320−1.872), hypertension (OR=1.579, 95%CI: 1.127−2.213), alcohol drinking (OR=1.286, 95%CI: 1.080−1.532), no physical exercise (OR=1.598, 95%CI: 1.330−1.920), sleep duration ≤ 6 h (OR=1.853, 95%CI: 1.518−2.263), sick leave in recent 6 months (OR=1.614, 95%CI: 1.226−2.123), physical fatigue (OR=2.384, 95%CI: 1.887−3.012), mental fatigue (OR=5.649, 95%CI: 4.382−7.283), combined exposure to occupational harmful factors (OR=1.329, 95%CI: 1.108−1.593), long-time sitting (OR=2.014, 95%CI: 1.271−3.190), and heavy lifting (OR=1.505, 95%CI: 1.178−1.923) showed a higher risk of reporting PMS (P<0.05). The C-index from the ROC curve of the nomogram model was 0.748 (95%CI: 0.729−0.766). The results of Bootstrap validation showed that the standard curve and the predicted curve almost overlapped, and the absolute error was 0.008, indicating that the model fitness was good. Conclusion PMS in female petrochemical workers may occur due to long-term exposures to multiple factors. The established nomogram model has good predictive ability and could be applied to monitor and evaluate female reproductive health in petroleum industry.

OBJECTIVE: To investigate the prognostic value of interim ¹⁸F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (△SUVmax%) cut-off value. The prognostic value of △SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum △SUV max% cut-off value was 74.9%. Patients with △SUVmax%≥74.9% had a lower rate of progression or recurrence than those with △SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). △SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). △SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), △SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that △SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION Both 5-PS and △SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of △SUVmax% is superior to that of 5-PS.
Fluorodeoxyglucose F18/therapeutic use* ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Prognosis ; Retrospective Studies ; Thiamine

The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval. Silencing PVT neurons inhibited extinction retrieval at recent time point (24 h after extinction), while activating them promoted extinction retrieval at remote time point (7 d after extinction), suggesting a critical role of the PVT in extinction retrieval. In the mPFC-PVT circuit, projections from IL rather than prelimbic cortex to the PVT were dominant, and disrupting the IL-PVT projection suppressed extinction retrieval. Moreover, the axons of PVT neurons preferentially projected to the CeL. Silencing the PVT-CeL circuit also suppressed extinction retrieval. Together, our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit.