ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

OBJECTIVE To elucidate the possible mechanism, and to explore the main components, core targets, and key signaling pathways of Haimufang Decoction(HMF) in treating non-small cell lung cancer(NSCLC) by the network pharmacology and serum pharmacology methods. METHODS TCMSP and DisGeNET databases were used to search and summarize the components, targets and non-small cell lung cancer-related targets of HMF, respectively. The common targets were obtained by intersection of drug targets and disease targets, and uploaded to the STRING data platform to construct a protein-protein interaction(PPI) network to screen core targets. GO and KEGG enrichment analysis of core targets were performed using DAVID database. Cytoscape 3.9.1 software was used to construct the network of "HMF flavor-components-targets-pathways", predicting the possible mechanisms of action of HMF. Finally, the cell cycle arrest and apoptosis induction experiments of HMF-containing serum on NSCLC NCI-H1975 cells were used to verify the effect of HMF on lung cancer and its potential mechanism. RESULTS A total of 65 compounds were identified from HMF, and 47 main compounds such as 24-keto-cholesterol, quercetin and diisobutyl phthalate were screened out. PPI network analysis shown that tumor protein p53, tumor necrosis factor, cystein-asparate protease-3 and other 55 proteins might be the core target proteins of HMF in the treatment of NSCLC, involving multiple signaling pathways such as pathways in cancer. In subsequent validation experiments, cell cycle arrest and apoptosis induction in the pathways in cancer pathway have been shown to be involved in the inhibition of non-small cell lung cancer. CONCLUSION HMF plays a role in the treatment of NSCLC through multi-component, multi-target and multi-channel signaling pathways, which provides a theoretical basis for the mechanism and clinical application of HMF.

Fermentum Rubrum（FR） is a kind of traditional Chinese medicine with dual-use functions of medicine and food， which has been used for more than 1 000 years. By referring to the ancient herbal classics and modern laws and regulations， the author sorted out the origin of FR， sorted out the development of processing， and analyzed the problems existing in the quality standard， aiming to provide a basis for further research and development of FR. There are many theories about the origin of FR. After summarizing and sorting out the relevant literature， three viewpoints are mainly drawn， including Han dynasty origin theory， Wei and Jin origin theory and Tang dynasty origin theory. After synthesizing the views of various schools， it is believed that the origin of FR should be no later than the Eastern Han dynasty. FR is made from rice by fermentation， which has the effect of strengthening the spleen， eliminating food， promoting blood circulation and removing stasis after fermentation. Although the natural fermentation in ancient times has been able to pay attention to the influence of temperature， humidity and strain on the quality of FR， due to the low level of science and technology， there are still problems such as complicated and cumbersome process， large workload and high labor cost. To the pure fermentation in modern times， the fermentation processing method of FR has been evolved， gradually improved and perfected. However， due to the lack of standardized research， there is no unified standard for the fermentation process of FR in various regions， and the quality standard lags behind seriously， which leads to the unstable product quality on the market. Among the 15 specifications for the preparation of FR， only 6 have been published in the past 5 years， and most of them have not been revised in a timely manner， and some of them have not been included in the updated version. Based on this， it is recommended to carry out a systematic study on processing technology of FR， and the best process is selected to accelerate the revision and improvement of its standardization， so as to improve the quality of FR sold in the market and promote its stable and sustainable development.

Objective:To summarize the incidence of cerebral venous reflux (CVR) in patients with recent small subcortical infarct (RSSI) and explore its correlation with enlarged perivascular spaces (EPVS).Methods:Patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022 were included. The baseline demographic data, medical history, and laboratory results of the patients were collected. CVR was assessed by time-of-flight magnetic resonance angiography. Patients were stratified into 2 groups based on the presence (CVR group) or absence of CVR (non-CVR group), and baseline characteristics as well as laboratory test results were compared between the 2 groups. The location and number of EPVS were evaluated using a visual grading scale, with EPVS with higher scores defined as high-grade EPVS (HEPVS). Simultaneous evaluation of cerebral white matter hyperintensities and lacunar infarctions was conducted, followed by intergroup comparisons. The relationship between EPVS and CVR was studied using multiple Logistic regression analysis.Results:A total of 571 patients with RSSI in the lentiform artery area were ultimately included, including 180 females (31.5%). Their age was (59.37±12.87) years. Among them, 73 patients (12.8%) exhibited CVR based on imaging findings, so the incidence of CVR was 12.8%. In comparison between the CVR group ( n=73) and the non-CVR group ( n=498), the proportion of females [21.9% (16/73) vs 32.9% (164/498), χ 2=3.578, P=0.059] was lower and the proportion of history of smoking [38.4% (28/73) vs 27.7% (138/498), χ 2=3.499, P=0.061] was higher in the CVR group, but without statistical significance. Additionally, the history of alcohol consumption [34.2% (25/73) vs 21.7% (108/498), χ 2=5.621, P=0.018] and the proportion of patients with concomitant HEPVS in the basal ganglia area [41.1% (30/73) vs 25.3% (126/498), χ 2=7.999, P=0.005] was higher in the CVR group with statistical significance. Multiple Logistic regression analysis showed that HEPVS in the basal ganglia region remained independently associated with CVR ( OR=1.988, 95% CI 1.190-3.320, P=0.009). Conclusion:EPVS in the basal ganglia region is significantly associated with CVR in the RSSI population, suggesting that venous dysfunction may be closely related to the formation of EPVS.

Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Objective:To explore the significance of CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage in the treatment of hypertensive basal ganglia cerebral hemorrhage.Methods:The clinical data of 60 patients with hypertensive basal ganglia cerebral hemorrhage, who underwent CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage in Beijing Luhe Hospital, Capital Medical University from January 2018 to December 2022, were retrospectively analyzed. The surgical related indexes and adverse reactions were recorded. The patients were followed up for 6 months, and the prognosis was evaluated using the Glasgow outcome score (GOS).Results:A total of 60 cases of CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage were all successfully performed, and the operation time was (53 ± 18) min. There were 2 cases (3.3%) of postoperative puncture path hematoma, which were completely resolved with conservative treatment. The expansion of postoperative intracerebral hematoma was not observed. The drainage tube retention after operation ≤2 d was in 44 cases (73.3%), and the drainage tube retained for 3 to 4 d was in 16 cases (26.7%), all of them had no intracranial infection after operation. Fifteen cases (25.0%) were complicated with severe pneumonia after operation, and 2 cases (3.3%) died due to severe pneumonia combined with multiple organ failure. Follow up at 6 months after operation, 17 cases (28.3%) were good, 19 cases (31.7%) had mild disability, 16 cases (26.7%) had severe disability, 6 cases (10.0%) had vegetative survival status, and 2 cases (3.3%) died.Conclusions:The CAS-R-2 frameless brain stereotactic instrument assisted trepanation and drainage for the treatment of hypertensive basal ganglia cerebral hemorrhage has the characteristics of simple operation, accurate positioning, minimal trauma, and fewer complications. It is a safe and effective method for treating hypertensive basal ganglia cerebral hemorrhage.

Objective:To construct a comprehensive and targeted risk assessment index system for central venous catheter (CVC) dysfunction in patients undergoing continuous renal replacement therapy (CRRT) .Methods:The risk assessment indicators for CVC dysfunction in CRRT patients were determined based on literature review and Delphi expert consultation. From July to September 2023, 19 experts in hemodialysis were selected for expert consultation. Based on expert opinions and screening criteria, corresponding indicators were added, deleted, or modified. After the second round of consultation, the expert opinions tended to be consistent.Results:A total of 17 experts completed two rounds of consultation. In the two rounds of consultation, the effective response rates of the questionnaires were 89.5% (17/19) and 100.0% (19/19), respectively, and the expert authority coefficients were 0.87 and 0.88, respectively. The Kendall harmony coefficients were 0.131 and 0.138 ( P<0.05). The final risk assessment index system included seven primary indicators and 44 secondary indicators. Conclusions:The risk assessment index system for CVC dysfunction in CRRT patients constructed is scientific, reliable, and practical, which can provide reference for clinical medical and nursing staff to improve catheter risk management in CRRT patients.

Objective To investigate whether there are sex differences in inflammatory bowel disease(IBD)among the offspring of mice with IBD.Methods BALB/c female mice were randomly divided into Na?ve and DSS groups.The mice in the Na?ve group drank autoclaved water freely,and the DSS group freely drank 2％dextran sodium sulfate(DSS)for 7 days before it was replaced with autoclaved water for 10 days.A total of 3～4 cycles were applied,and the IBD female mice were paired with healthy male mice in cages.When the pups were 8 weeks old,they were divided into the Con group and IBD group.The Con group drank autoclaved water freely for 7 days,and the IBD group drank 3％DSS for 7 days.During the modeling period,disease activity index was scored by monitoring body weight,fecal consistency,and the presence of blood in stool every day.Pathological sections were taken to observe changes in goblet cells and the mucus layer of colon tissues.The concentrations of interleukin(IL)-6,IL-1β,IL-33,and IL-10 in the colon were detected by enzyme-linked immunosorbent assay.Real-time quantitative PCR was used to determine the mRNA expression levels of tight-junction proteins and MUC-2 in the colon.Results Compared with female IBD mice,male IBD mice had higher DAI scores,significantly shorter colons,larger amounts of inflammatory infiltrate,more crypt abnormalities,and a higher absence of goblet cells in the colon;their relative mRNA expression of occludin mRNA was significantly reduced,levels of IL-6 and IL-33 were significantly increased,and level of IL-10 was significantly decreased.Conclusions The symptoms of colitis in the offspring of IBD mice were more severe in male than in female mice,a result that was mainly attributed to the more severely impaired intestinal epithelial barrier function in males.

Objective To evaluate the dose distribution and execution accuracy of intensity-modulated radiation therapy(IMRT)plans with different minimum segment widths for patients with primary liver cancer,thereby providing reference for the radiotherapy planning.Methods A retrospective study was conducted on 30 patients with primary liver cancer.With the other optimization condition unchanged,5 IMRT plans with minimum segment widths of 0.6,0.8,1.0,1.2 and 1.5 cm were made for each patient,and the dose distribution,execution efficiency and gamma passing rate of the 5 plans were compared.Results The monitor units and delivery time of the 5 plans decreased with increasing minimum segment width,while the gamma passing rates at 3 mm/3%and 2 mm/2%tended to increase,with statistical differences(P<0.05).Conclusion The 5 plans in the study can be used for clinical treatment.While meeting the clinical requirements,reasonably setting the minimum segment width in IMRT plan can reduce monitor units,shorten delivery time,and improve treatment accuracy.

Osteoclasts are the only cells responsible for bone resorption in the body, and osteoblasts are the main cells responsible for bone regeneration in the body. Under physiological conditions, these cells maintain a dynamic balance to maintain bone homeostasis. It was widely believed that the imbalance of bone metabolism is mainly affected by the expression of related inflammatory factors. However, with the gradual expansion of related studies in recent years, autophagy has been shown to be closely related to the differentiation, apoptosis and functions of osteoclasts and osteoblasts. AMP-activated protein kinase (AMPK) is an important regulator of energy metabolism in vivo and is involved in the regulation of autophagy and bone homeostasis in bone metabolism-related cells. Periodontitis is a chronic infectious disease, and its typical symptoms are alveolar bone resorption. At present, controlling the level of periodontal inflammation and alveolar bone resorption more effectively in clinical practice remains a challenge. The detection of AMPK and autophagy levels in bone metabolism-related cells shows certain prospects for the clinical prevention and treatment of periodontitis in the future. Therefore, this article reviews the regulation of periodontal inflammation levels and bone homeostasis through cell autophagy related to AMPK-mediated bone metabolism.