Mechanism of Ruanmai decoction in treating atherosclerosis based on YWHAZ/p38MAPK/CASP3 signaling pathway / 中国药理学通报

Aim To explore the mechanism of action of Ruanmai decoction in treating atherosclerosis through network pharmacology. Methods The chemical components and targets of Ruanmai decoction were queried using TCMSP. Relevant targets for atherosclerosis were retrieved from DrugBank, GeneCards, OMIM, and TTD databases. The " Drug-Active Ingredient-Target" PPI network was constructed using Cyto-scape software. GO and KEGG enrichment analysis were performed using the David database. Molecular docking verification of key components with core targets was conducted using the Seesar software. Atherosclerosis mouse models were established by feeding ApoE mice with a high-fat diet, and Ruanmai decoction granules were administered orally. Aortic pathological sections were stained, blood lipids were measured, and immunofluorescence was used to detect Mac2 and YWHAZ protein expression. Western blot was used to detect p-p38MAPK and C-CASP3 protein expression. Results Ruanmai decoction screened a total of 72 active drug components corresponding to 168 target genes for the treatment of atherosclerosis. The targets were primarily enriched in biological processes related to lip-id metabolism, inflammation and immunity, oxidative stress, vascular endothelial function, cell proliferation and apoptosis, glycolysis, and ubiquitination. Signaling pathways such as МАРК, TNF, PDK-Akt, and IL-17 were also involved. Animal experiments verified that RMJ could regulate the p38MAPK signaling pathway by down-regulating key targets YWHAZ, p-p38MAPK, and C-CASP3, thereby reducing AS inflammation and inflammation-induced apoptosis. Conclusions Ruanmai decoction can inhibit the expression of YWHAZ and activate the p38MAPK signaling pathway, potentially improving vascular inflammation, lipid metabolism, oxidative stress, and other pathological processes by regulating the МАРК, TNF, PDK-Akt, and IL-17 signaling pathways, thus preventing and treating atherosclerosis.

Regulatory Mechanism of Radiation Therapy for Lung Cancer with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Lung cancer is the fastest-growing cancer type in terms of incidence and mortality worldwide， posing a huge threat to the health and life of the population. Radiation therapy is one of the main methods for treating lung cancer， and there is a clear dose-effect relationship between the radiation dose and local control rate of lung cancer. However， the lung is a radiation dose-limiting organ， and the radiation resistance of lung cancer tissues and the radiation damage to normal tissues limit the radiation efficacy for lung cancer. The pathogenesis of lung cancer in traditional Chinese medicine （TCM） is characterized by an initial deficiency in vital Qi， followed by the internal invasion and gradual accumulation of pathogenic Qi. After radiation therapy for lung cancer， the body's vital Qi becomes weaker， and syndromes of phlegm coagulation， Qi stagnation， and static blood blocking collaterals become more severe， leading to radiation resistance of lung cancer tissues. Therefore， the key issue to better clinical efficacy of radiation therapy for lung cancer patients is to use drugs to enhance the radiation sensitivity of lung cancer cells and improve the radiation tolerance of normal lung tissues. TCM can be used as a radiation sensitizer by regulating the cell cycle to increase the proportion of cells in the radiation-sensitive phase， promoting upregulation of pro-apoptotic genes and downregulation of anti-apoptotic genes to induce cell apoptosis， enhancing DNA damage caused by radiation and inhibiting damage repair， improving blood circulation and tissue oxygen supply， and so on， to enhance the sensitivity of tumor cells to radiation and amplify the toxicity of radiation to tumor tissues. TCM can also be used as a radiation protector by inhibiting cell damage， regulating cytokines and immune balance， reducing the release of inflammatory and fibrotic factors， and inhibiting the activation of related signaling pathways to prevent and treat radiation-induced lung injury. This article systematically reviewed the research results of TCM on radiation sensitization and radiation protection in lung cancer in recent years， aiming to elucidate the mechanism of TCM in regulating the effect of radiation therapy for lung cancer and provide more theoretical and practical basis for TCM to participate in improving the prognosis of lung cancer patients undergoing radiation therapy.

Comparison of the control effect of corneal refractive therapy with vision shaping treatment designed orthokeratology on corneal morphology myopia at low E-values / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe and analyze the effectiveness and safety of wearing corneal refractive therapy(CRT)and vision shaping treatment(VST)designed orthokeratology in controlling myopic progression in adolescents with low E-value corneal morphology.METHODS: This prospective study involved 100 cases(100 eyes)of adolescent myopia patients fitted with orthokeratology at our optometry clinic from January 2020 to December 2021. The data of right eye were collected for research, and they were divided into low myopia group(-1.00 to -3.00 D)and moderate myopia group(-3.25 to -5.00 D)according to spherical equivalent, with 50 cases in each group. Each group of patients was further randomly divided into the CRT group and the VST group, with 25 cases in each group. Uncorrected visual acuity, refractive error, axial length(AL), tear film break-up time(BUT), corneal endothelial cell density, corneal staining grading, lens decentration, and refractive power at 15°-30° were measured before and after wearing orthokeratology, with a follow-up duration of 1.5 a.RESULTS: The uncorrected visual acuity of CRT and VST subgroups in the low myopia group showed no statistical significance at any time point after wearing orthokeratology. However, in the moderate myopia group, CRT subgroup showed better uncorrected visual acuity than the VST subgroup, with significant differences at 1 d and 1 wk(t=-9.474, -12.067, both P<0.01); no significant differences were noted at other time points. After wearing lens for 6 mo and 1.5 a, the AL growth for the CRT subgroup in low and moderate myopia was less than the VST subgroup, with no statistically significant differences. There were no statistically significant differences in binocular BUT and corneal endothelial cell density after wearing lens for 6 mo and 1.5 a. Corneal injury was lower in the CRT subgroup than that in the VST subgroup, but the difference was not statistically significant(Z=-1.803, P=0.071). Lens decentration was significantly better in the CRT subgroup than in the VST subgroup(Z=-4.629, P<0.001). In the periphery of the retina at 15°-30°, there were no significant differences in the amount of myopic defocus between the two groups, while it was statistically significant at 1, 3, and 6 mo in the moderate myopia subgroup(t=-3.949, P=0.008; t=-5.833, P<0.001; t=-6.231, P<0.001), indicating that CRT subgroup could produce a greater amount of myopic defocus.CONCLUSION: For patients with low E-value corneal morphology, CRT, using the vector height at 8 mm on the cornea for fitting, is not limited to the corneal E-value. It shapes faster and improves uncorrected visual acuity after shaping, especially for moderate myopia, achieving better daytime vision. In terms of controlling myopia, CRT fitting elevates return zone depth(RZD), creating a small central optical zone to produce more peripheral myopic defocus. However, there was no significant difference between the two groups in controlling AL growth. Both groups showed minimal corneal damage, indicating consistent safety in myopia control.

Effects of co-culture of dendritic cells loaded with MAGE-A3 antigen and cytokine-induced killer cells on tumor stem cells and malignant progression of endometrial cancer / 中国临床药理学与治疗学

AIM: To explore the effects of dendritic cells (DC) and cytokine-induced killer cells (CIK) carrying melanoma-associated antigen gene A3 (MAGE-A3) on endometrial cancer tumor stem cells and malignant progression. METHODS: Human peripheral blood was collected to separate mono-nuclear cells, and DC and CIK cells were induced by cytokines, respectively. DCs were incubated with MAGE-A3 and then co-cultured with CIK, and the phenotypes of DC-CIK and MAGE-A3-DC-CIK were detected by flow cytometry; The CD133

Analysis on Feasibility of Electronic Nose Technology for Rapid Identification of Bletillae Rhizoma and Its Approximate Decoction Pieces / 中国实验方剂学杂志

ObjectiveTo investigate the feasibility of applying electronic nose technology to rapidly identify Bletillae Rhizoma and its approximate decoction pieces. MethodA total of 134 batches of Bletillae Rhizoma and its approximate decoction pieces， including 45 batches of Bletillae Rhizoma， 30 batches of Gastrodiae Rhizoma， 30 batches of Polygonati Odorati Rhizoma and 29 batches of Bletillae Ochraceae Rhizoma， were collected as test samples. The olfactory sensory data of the samples were collected by PEN3 electronic nose as the independent variable（X）. Based on the identification results of the 2020 edition of Chinese Pharmacopoeia and local standards， as well as the high performance liquid chromatography（HPLC） fingerprint and original purchase information of 134 batches of the decoction pieces， the benchmark data Y of the identification model were obtained， and four chemometric methods of principal component analysis-discriminant analysis（PCA-DA）， partial least squares-discriminant analysis（PLS-DA）， least square-support vector machine（LS-SVM） and K-nearest neighbor（KNN） were used to establish the binary identification model for 45 batches of Bletillae Rhizoma and 89 batches of non-Bletillae Rhizoma and the quadratic identification model of the four kinds of decoction pieces， that is， Y=F（X）. ResultAfter leave-one-out cross validation， the positive discrimination rates of the above four models were 97.01%， 97.01%， 98.51% and 97.01% in the binary identification， and 97.76%， 89.55%， 98.51% and 97.01% in the quadratic identification， respectively. The highest positive discrimination rate could reach 98.51% for the binary and quadratic identification models， and LS-SVM algorithm is both the optimal one， the most suitable kernel functions were chosen as radial basis function and linear kernel function， respectively. The optimal models discriminated well with no unclassified samples. ConclusionElectronic nose technology can accurately and rapidly identify Bletillae Rhizoma and its approximate decoction pieces， which can provide new ideas and methods for rapid quality evaluation of other decoction pieces.

Nusinersen treatment in patients with spinal muscular atrophy: A safety analysis of laboratory parameters / 西安交通大学学报(医学版)

【Objective】 To explore the changes of laboratory parameters and safety of nusinersen in the treatment of spinal muscular atrophy (SMA). 【Methods】 Retrospective analysis was made on the six SMA patients treated with nusinersen in the Department of Neurology at The First Affiliated Hospital of Xi’an Jiaotong University from December 2021 to December 2022. We summarized the patients’ clinical data, including genetic diagnosis results, disease classification, and clinical manifestations. Intrathecal injection of 5 mL/12 mg of nusinersen administered on the 1st, 14th, 28th, and 63rd days, followed by maintenance treatment every 4 months. After each administration, we compared and evaluated the patients’ cerebrospinal fluid, blood routine, liver function, kidney function, and coagulation function with baseline values. We regularly followed up the patients and recorded adverse reactions after administration to evaluate medication safety. 【Results】 A total of six patients were diagnosed with SMA, including four cases of SMA3 type and two cases of SMA4 type. The deletion of exon 7 of the survival motor neuron gene 1 (SMN1) in patients led to changes in motor neuron, most of which were caused by limb weakness; in severe cases, the patients were unable to stand. The baseline abnormal test indicators of patients included the increase of cerebrospinal fluid lactate dehydrogenase (CSF-LDH), the increase of creatine kinase (CK), and the decrease of creatinine (Cr). After four times of treatment, the patients’ CSF-WBC, CSF-Glu, CSF-Pro, CSF-LDH, WBC, PLT, RBC, ALT, AST, GGT, BUN, uric acid (UA), INR, aPTT, and D-dimer had no significant difference from the baseline (P>0 05). The patients had no other significant adverse reactions except headaches, dizziness, and back pain after puncture. 【Conclusion】 Nusinersen has good safety on SMA patients.

Applicability Analysis of Gender Selection in Mitochondrial Replacement Technology / 中国医学伦理学

Whether gender selection should be conducted is a controversial topic in ethical research on mitochondrial replacement technology. Scholars put forward different moral judgments based on different positions, and after reviewing these judgments, it was found that those who support gender selection mainly rely on the utility theory and rights theory, while those who oppose gender selection mainly rely on the dignity theory and community theory. It is not difficult to find that relying on traditional moral theory to defend moral judgments or actions often leads to endless debates among "moral strangers" , and does not provide effective guidance for solving specific problems. Principlism is a systematic and comprehensive analytical approach constructed with a series of clear and effective frameworks, which can reasonably solve the differences and disagreements between different value systems and cultural concepts. In the discussion of whether gender selection should be conducted in mitochondrial replacement technology, principlism refined and balanced it through the method of reflective equilibrium, and finally obtained the best judgment plan that allows for gender selection. To truly achieve the humane purpose of avoiding harm in gender selection, it is necessary to clearly limit the objects and stages of use, and regulate them from the dual dimensions of ethics and morality, as well as policy regulation.

Effect of recombinant human coagulation factor Ⅶa combined with Bakri balloon compression on oxidative stress and coagulation in patients with refractory postpartum hemorrhage / 中国输血杂志

【Objective】 To investigate the effects of recombinant human coagulation factor Ⅶa combined with Bakri balloon compression on oxidative stress and coagulation in patients with refractory postpartum hemorrhage. 【Methods】 Prospectively, 80 patients with refractory postpartum hemorrhage in Chengdu Fifth People′s Hospital from June 2019 to June 2022 were selected and grouped according to the random number table method. The control group (n=40) was treated with Bakri balloon compression, and the observation group (n=40) was treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression. The bleeding-related indexes and adverse effects were observed in both groups, and the prenatal and 24 h postpartum oxidative stress, coagulation function and inflammatory factors were compared between the two groups. 【Results】 The blood loss in the observation group and the control group was (683.96±146.52) vs(796.63±152.41)mL during operation, (812.46±161.53) vs(965.39±166.22)mL in 2 h after delivery, (899.53±178.74) vs(1 084.31±203.67)mL in 24 h after delivery, and the transfusion volume was (512.31±104.76) vs(683.25±113.52)mL, and the onset time of hemostasis was (14.63±3.18) vs (21.72±5.29) min (P0.05). At 24 h postpartum, NE, Cor, SOD and MDA were higher than those before delivery in both groups, but the observation group was lower than the control group (P<0.05); TT, APTT and PT were longer and Fib was lower in both groups than before delivery, but TT, APTT and PT were shorter and Fib was higher in the observation group than in the control group (P<0.05); CRP, IL-8 and TNF-α were higher in both groups than before delivery, but the observation group was lower than in the control group (P<0.05). 【Conclusion】 Hemostasis in patients with refractory postpartum hemorrhage treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression was effective, which can improve coagulation, reduce transfusion, decrease oxidative stress injury and inflammatory response without increasing adverse effects.

Communication and cooperation within a stroke rehabilitation team: a qualitative research / 中国康复理论与实践

ObjectiveTo explore the obstacles and causes of communication and cooperation among doctors, nurses and rehabilitation therapists in a stroke rehabilitation team. MethodsFrom July to October, 2022, twelve rehabilitation evaluation meetings were observed using ethnographic research, based on Shared Mental Model theory. Semi-structured interviews were held with five doctors, ten nurses and four rehabilitation therapists. ResultsFour themes and nine sub-themes were presented, namely equipment (poor interoperability of information system, limited knowledge of rehabilitation equipment for doctors and nurses), task (members were under time pressure to attend meeting, imperfect inter-discipline communication system), team interaction (insufficient information sharing, unfamiliar with roles/responsibilities, misunderstanding between specialties) and team member (less participation of nurses, limited multidisciplinary knowledge). ConclusionThe communication and cooperation among stroke rehabilitation team members is limited by many factors, such as equipment, task, team interaction and team members. It is suggested to improve interoperability of information systems, create a supportive environment, know each other's roles/responsibilities, strengthen interdisciplinary crossover, pay attention to and support the cultivation of nurses' ability, to promote efficient communication and cooperation among team members.

Association between HLA-DRB1 gene polymorphisms and genetic susceptibility of early-onset severe preeclampsia / 中国当代儿科杂志

OBJECTIVES@#To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE).@*METHODS@#Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups.@*RESULTS@#Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05).@*CONCLUSIONS@#The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.

Comparison of posterolateral approach and combined approach in treatment of Mason type 2B posterior malleolar fracture / 中国修复重建外科杂志

OBJECTIVE@#To compare the effectiveness between the posterolateral approach and the posterolateral combined posteromedial approaches in the treatment of Mason type 2B posterior malleolar fracture.@*METHODS@#A retrospective analysis was performed on the clinical data of 79 patients with posterior ankle fracture who met the selection criteria between January 2015 and January 2022. There were 62 cases of Mason 2B Pilon subtype and 17 cases of avulsion subtype. Among Mason 2B Pilon subtype patients, 35 were treated with posterolateral approach (group A), 27 patients were treated with combined approach (group B). There was no significant difference in gender, age, injured side, cause of injury, time from injury to operation, preoperative hospital stay, preoperative visualanalogue scale (VAS) score, and intraoperative internal fixation between the two groups ( P>0.05). All patients with Mason 2B avulsion subtype were treated by posterolateral approach, including 7 males and 10 females, aged from 25 to 68 years, with an average of 46.1 years. The operation time, intraoperative blood loss, postoperative hospital stay, and complications were recorded. The reduction quality was evaluated by Ovadia deals radiographic score, and the ankle function and pain were evaluated by VAS score, American Orthopaedic Foot and Ankle Society (AOFAS) score, and ankle range of motion.@*RESULTS@#Mason 2B Pilon subtype: There was no significant difference in operation time, intraoperative blood loss, postoperative hospital stay, and follow-up time between the two groups ( P>0.05). The radiological evaluation of Ovadia deals in group A was significantly worse than that in group B ( P<0.05). The VAS score in the two groups significantly improved at each time point after operation, and the VAS score and AOFAS score further improved with the extension of time after operation, and the differences were significant ( P<0.05). Except that the AOFAS score of group A was significantly lower than that of group B at last follow-up ( P<0.05), there was no significant difference in VAS score and AOFAS score between the two groups at other time points ( P>0.05). At last follow-up, the ankle range of motion in group A was significantly less than that in group B ( P<0.05). There was no significant difference in the incidence of sural nerve injury, deep tissue infection, limitation of toe movement, and traumatic ankle arthritis between the two groups ( P>0.05). Mason 2B avulsion subtype: The operation time was (119.47±20.61) minutes and the intraoperative blood loss was 50 (35, 55) mL. Seventeen patients were followed up 13-25 months, with an average of 18 months. The Ovadia deals score was excellent in 10 cases, good in 6 cases, and poor in 1 case at 1 week after operation, and the excellent and good rate was 94.1%. All fractures healed in 8-18 weeks with an average of 12.35 weeks. There were 1 case of sural nerve injury and 3 cases of traumatic ankle arthritis after operation. No deep tissue infection or limitation of toe movement occurred. The VAS score decreased significantly and AOFAS score increased significantly with time, and the differences were significant between different time points before and after operation ( P<0.05). The ankle range of motion at last follow-up was (56.71±2.47)°.@*CONCLUSION@#Compared with the posterolateral approach, the combined approach is a better choice for the treatment of Mason 2B Pilon subtype. If the posteromedial bone block does not affect the reduction of the medial malleolus, the posterolateral approach can achieve good effectiveness for Mason 2B avulsion subtype.

Isolation and identification of chemical constituents from aerial parts of Glycyrrhiza uralensis / 中国中药杂志

The present study investigated the chemical constituents from the aerial parts of Glycyrrhiza uralensis. The ethanol extract of the aerial parts of G. uralensis was separated and purified by different column chromatographies such as macroporous resin, silica gel, and Sephadex LH-20, and through preparative HPLC and recrystallization. Thirteen compounds were isolated and identified as(2S)-6-[(Z)-3-hydroxymethyl-2-butenyl]-5,7,3'-trihydroxy-4'-methoxy-dihydroflavanone(1),(2S)-8-[(E)-3-hydroxymethyl-2-butenyl]-5,7,3',5'-tetrahydroxy-dihydroflavanone(2), α,α'-dihydro-5,4'-dihydroxy-3-acetoxy-2-isopentenylstilbene(3), 6-prenylquercetin(4), 6-prenylquercetin-3-methyl ether(5), formononetin(6), 3,3'-dimethylquercetin(7), chrysoeriol(8), diosmetin(9),(10E,12Z,14E)-9,16-dioxooctadec-10,12,14-trienoic acid(10), 5,7,3',4'-tetrahydroxy-6-prenyl-dihydroflavanone(11), naringenin(12), dibutylphthalate(13). Compounds 1-3 are new compounds, and compounds 10 and 13 are isolated from aerial parts of this plant for the first time.

Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study / 北京大学学报(医学版)

OBJECTIVE@#To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study.@*METHODS@#A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

Effects of Akkermansia on AOM/DSS Inflammatory-associated Colorectal Cancer / 肿瘤防治研究

Objective To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells. Methods AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR. Results Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated. Conclusion AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.

Establishment of a screening cell model for cannabinoid type 1 receptor agonists / 药学学报

Cannabinoid receptors are one of the most expressed G protein-coupled receptors in the central nervous system, which are potential drug targets for inflammation, pain and drug abuse. Cannabinoid receptors are composed of type 1 receptor (CB1R), type 2 receptor (CB2R) and other receptors, of which CB1R plays a vital role in regulating central memory, cognition, and motor function. Therefore, screening CB1R agonists has potential value in treating nervous system diseases. In this study, the intracellular loop 3 (ICL3) domain of CB1R was replaced with a circular-permutated enhanced green fluorescent protein (cpEGFP). After infecting HEK 293T cells with lentivirus particles, we obtained a stable cell line that was overexpressed human CB1R-cpEGFP after puromycin selection. The interaction between receptor agonists and CB1R led to the change of receptor conformation, resulting in de-protonation of the EGFP, and enhancing the fluorescence intensity. Therefore, active CB1R compounds could be verified by measuring the fluorescence intensity. Using CB1R agonist arachidonyl-2′-chloroethylamide (ACEA) as a positive control to evaluate the reliability of this model, studies have shown that ACEA could induce receptor activation and increase fluorescence intensity, while antagonist rimonabant inhibited receptor activation with unchanged fluorescence intensity. In conclusion, this study successfully constructed a fluorescent probe screening model for CB1R agonists.

Clinical characteristics and treatment of patients with acute acquired concomitant esotropia in different refractive status / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the clinical characteristics and treatment of patients with acute acquired concomitant esotropia(AACE)in different refractive status.METHODS: A retrospective analysis was conducted on 110 patients with non-type I AACE treated from January 2020 to January 2022. The non-myopic group(30 cases, spherical equivalent&#x003E;-0.5D)and the myopic group(80 cases, spherical equivalent≤-0.5D)were divided according to the refractive status. The degree of deviation, accommodative convergence and accommodation ratio(AC/A), visual function, and surgical methods were observed. RESULTS: The non-myopic group had no difference in the degree of near deviation [(47.13±23.54)△] and the degree of distant deviation [(48.90±22.59)△](P&#x003E;0.05); near deviation [(40.49±26.09)△] of myopic group was less than distant deviation [(50.09±25.41)△](P&#x003C;0.001); and there was no difference in the same distance between the two groups(P&#x003E;0.05). AC/A in the non-myopic group(5.40±2.23)was higher than that in the myopic group(3.14±3.10; P&#x003C;0.05). Patients in the myopic group had better near stereopsis than the non-myopic group(P&#x003C;0.05). The non-myopic group had a variety of surgical methods, while the myopic group mostly used lateral rectus resection or/and medial rectus recession.CONCLUSION: AACE can occur in different refractive status. Non-myopic patients have the same degree of distant and near strabismus, high AC/A, and varied surgical methods. However, myopic patients have less degree of near deviation than distant deviation and have normal AC/A and better near stereopsis, and lateral rectus resection or/and medial rectus recession are commonly used.

Analysis of Formulation and Characteristics of Provincial Standards for Traditional Chinese Medicine Dispensing Granules / 中国实验方剂学杂志

In order to standardize the quality control of traditional Chinese medicine（TCM） dispensing granules， the Chinese Pharmacopoeia Commission has promulgated and implemented 200 national drug standards for TCM dispensing granules， but there are still varieties of TCM dispensing granules without unified standards. Many provinces have actively invested in the formulation of provincial standards for TCM dispensing granules to make up for the gaps in standards for varieties of traditional Chinese medicine dispensing granules other than the national standards. By the end of July 2022， 29 provincial-level administrative regions have successively promulgated and implemented a total of 5 602 provincial standards for TCM dispensing granules， involving more than 400 varieties. In order to better understand the formulation and characteristics of provincial standards， this study took 105 provincial standards that have been promulgated and implemented in Henan province as an example， and comprehensively analyzed the formulation and characteristics through quality control indicators such as dry extract rate of raw materials， contents of index components and their transfer rates， specifications and so on. The formulation and characteristics of the same TCM dispensing granules in the provincial standards of different provinces were further analyzed， in order to provide reference for the formulation of provincial standards of TCM dispensing granules and the implementation of national standards.

HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.

Evaluation of anticholinergic burden in elderly outpatients and the risk factors / 中南大学学报(医学版)

OBJECTIVES@#The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs.@*METHODS@#A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia.@*RESULTS@#A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine).@*CONCLUSIONS@#There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation / 中国中药杂志

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.