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.

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.

Application of discrete event simulation model in analysis on cost-effectiveness of epidemiology screening / 中华流行病学杂志

Discrete event simulation (DES) model is based on individual data, by which discrete events over time are simulated to reflect disease progression. The effects of individual characteristics on disease progression could be considered in the DES model. Moreover, unlike state-transition models, DES model without setting of fixed cycle can contribute to more accurate estimation of event time, especially in the evaluation of the long-term effectiveness of screening strategies for complex diseases in which time dimension needs to be considered. This article introduces the general principles, construction steps, analytic methods and other relevant issues of the DES model. Based on a research case of estimating the cost-effectiveness of screening for abdominal aortic aneurysms in women aged 65 years and above in the United Kingdom, key points in applications of the DES model in analysis on effectiveness of complex disease screening are discussed in detail, including model construction and analysis and interpretation of the results. DES model can predict occurring time of discrete events accurately by establishing the distribution function of their occurring time and is increasingly used to evaluate the screening strategies for complex diseases in which time dimension needs to be considered. In the construction of DES model, it is necessary to pay close attention to the clear presentation of model structure and simulation process and follow the relevant reporting specification to conduct cost-effectiveness analysis to ensure the transparency and repeatability of the research.

Effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis / 中国血吸虫病防治杂志

Objective To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. Methods A “admission-hospitalization-discharge” whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. Results The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = −7.688, −3.576 and −4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ2 = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ2 = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ2 = 11.767, P < 0.01). Conclusions The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients’ cure.

Clinical characteristics and progression risk factors for patients with monoclonal gammopathy of undetermined significance / 中华血液学杂志

Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.

Effectiveness of Longji Daoyin exercise on adolescents of mild idiopathic scoliosis / 中国学校卫生

Objective@#To explore the effectiveness of spinal guidance exercise on adolescents of mild idiopathic scoliosis, so as to provide an experimental reference and method for promoting adolescents spinal health.@*Methods@#From the scoliosis screening, 96 children who met the diagnostic criteria were selected in June 2021, and were divided into the experimental group and the control group, with 48 cases in each group. The experimental group received a 12 week Longji Daoyin exercise training, and the control group received health education, observation and monitoring. Before and after the experiment, the axial trunk rotation (ATR) and scoliosis Cobb angle of the two groups were tested respectively, and the subjective sensation of the patients was measured by Scoliosis Research Society-22(SRS-22) questionnaire.@*Results@#After 12 weeks, the ATR and Cobb angles of the experimental group decreased [( 5.02± 2.85，7.59±3.94)°]，compared to (7.08±2.84)° and (15.84±2.00)° before intervention( t =14.02, 17.09, P < 0.01 ). Scores of functional activity, self image and mental health in the SRS-22 score increased from (4.65±0.14)(3.49±0.21) and (3.99±0.17) to(4.77±0.14)(4.62±0.13)(4.42±0.13)( t =-4.86,-39.12,-13.92, P <0.01 ). The ATR and Cobb angles of the control group increased from (6.94±2.15)° and (15.82±1.76)° to (8.25±2.49)° and (18.63±3.12)°( t =7.44,8.99, P <0.01), and the scores of self image and mental health in the SRS-22 score decreased from (3.49±0.19) and (4.00±0.15) to (3.44±0.18) and (3.94±0.14)( t =-3.74,-4.39, P <0.05).@*Conclusion@#Early adolescent idiopathic scoliosis is easy to aggravate during the observation period. Longji Daoyin exercise is of preventive and therapeutic significance.

Efficacy comparison of Jensen and augmented Hummelsheim procedure in the treatment of complete paralytic esotropia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficacy of Jensen and augmented Hummelsheim procedures in the treatment of complete paralytic esotropia.METHOD: A total of 35 patients(44 eyes)who were diagnosed with complete paralytic esotropia from October 2016 to October 2020 were retrospectively analyzed, of which 15 cases(21 eyes)underwent Jensen procedure combined with recession of antagonist muscle(Jensen procedure group), and 20 cases(23 eyes)received augmented Hummelsheim procedure combined with recession of antagonist muscle(Hummelsheim procedure group). The operation time, preoperative and postoperative esotropia deviation, degree of abduction paralysis, recession of medial rectus muscle and cure rate were observed.RESULTS: Clinical data and operation time of the patients in two groups were not statistically significant(P &#x0026;#x003E;0.05). During the last follow-up, the esotropia deviation of Jensen procedure group decreased from 102.33±41.70PD to 3.93±4.82PD(P&#x0026;#x003C;0.001), and it decreased from 94.75±33.03PD to 2.85±5.96PD in Hummelsheim procedure group(P&#x0026;#x003C;0.001), while the degree of abduction paralysis were significantly improved from -4.81±0.40 to -1.57±0.51 in the Jensen procedure group(P&#x0026;#x003C;0.001)and from -4.91±0.29 to -1.22±0.42 in Hummelsheim procedure group(P&#x0026;#x003C;0.001). Besides, there was no statistical difference in postoperative esotropia deviation between the two groups(P&#x0026;#x003E;0.05), but the degree of postoperative abduction paralysis in the Hummelsheim procedure group was significantly better than that of Jensen procedure group(P&#x0026;#x003C;0.05). The recession of medial rectus muscle of the two groups were 7.16±2.07 and 6.37±2.34 mm, respectively(P&#x0026;#x003E;0.05). During the last follow-up, in the Jensen procedure group, 2 patients were undercorrection(+10PD and +12PD respectively)and 13 cases(87%)were cured. In the Hummelsheim procedure group, 1 patient was undercorrection(+25PD)and 19 patients were cured(95%), and there was no statistical significance in cure rates of the two groups(P=0.565).CONCLUSIONS: Both Jensen procedure and augmented Hummelsheim procedure can effectively treat complete paralytic esotropia, and the latter is more effective in improving the abduction paralysis.

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.

Research on strategies to improve the social co-governance of food safety / 上海预防医学

Shanghai municipal administration of market supervision focuses on "the people's city built by the people， and the people's city for the people". Through the regular "you order， I inspect" activities on food safety the administration has established an important window for disseminating market regulation information， showcasing the image of market regulation， and telling the story of market regulation. Over the past three years， by combining the needs of the citizens in Shanghai and the routine food safety spot-checking plan through the food safety “you order，I inspect” activities， the administration has enabled the public to perceive and evaluate the quality of the inspection services， and has actively built a food safety social co-governance service brand. While ensuring that people can eat at ease and buy at will， we will also boost consumer confidence and promote high-quality development of food safety， so as to create a vivid picture of people participating in and benefiting from food safety governance.

Relationship between myocardial viability and early application of intra-aortic balloon pump after coronary artery bypass grafting / 中国胸心血管外科临床杂志

@#Objective    To explore the relationship between myocardial viability in patients with coronary artery disease who underwent elective coronary artery bypass grafting (CABG) and early application of intra-aortic balloon pump (IABP) after coronary revascularization, and to provide relevant clinical reference for the pre-implantation of 16G single-lumen catheter in the femoral artery of high-risk patients to facilitate the addition of IABP after operation. Methods    This retrospective study included 521 patients (414 males and 107 females, aged 62.50±8.82 years) who underwent positron emission tomography (PET)-computed tomography (CT) perfusion-metabolism imaging prior to CABG surgery in our institution from December 2015 to August 2020. The myocardial viability information and left ventricular functional parameters were measured, including the proportion of non-viable myocardium (perfusion-metabolic imaging match), hibernating myocardium (perfusion-metabolic imaging mismatch) and dysfunctional myocardium (non-viable+viable myocardium), left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume (LVESV). The patients were divided into an IABP group and a non-IABP group  according to whether they received IABP treatment after revascularization. The clinical data were reviewed and compared to explore significant impact factors between the two groups. And the multivariate logistic regression analysis was performed to investigate the correlation between preoperative myocardial viability and early use of IABP after CABG. Results    In multivariate logistic regression analysis, the amount of non-viable, dysfunctional myocardium and LVESV value were identified as the independent predictors for the probability of IABP use in the initial postoperative period. Receiver operating characteristic analysis showed that 9.5% non-viable myocardium, 19.5% dysfunctional myocardium, and LVESV of 114.5 mL were the optimal cutoff for predicting early IABP implantation during CABG. Conclusion    The myocardial survival status displayed by preoperative PET-CT myocardial perfusion-metabolism imaging can predict the possibility of applying IABP in CABG perioperative period. In addition to routine pre-anesthesia assessment, anesthesiologists can conduct risk stratification assessment for patients with CABG according to the results of preoperative myocardial viability imaging, which is of great significance to ensure the perioperative safety of high-risk patients with CABG.

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.

Protein phosphatase 4 catalytic subunit (PP4C) increases hepatitis B virus X protein levels and promotes its biological functions / 中华微生物学和免疫学杂志

Objective:To investigate the role of protein phosphatase 4 catalytic subunit (PP4C) in regulating hepatitis B virus X protein (HBx) levels and its effects on the biological functions of HBx, thus to provide a potential therapeutic targets for hepatitis B virus (HBV)-related hepatocellular carcinoma.Methods:In vivo and in vitro interactions between HBx and PP4C were analyzed by co-immunoprecipitation (Co-IP) and GST pull-down assay. Recombinant plasmids of PP4C and HBx were co-transfected with Lipofectamine 3000 reagents into hepatoma cells to detect the protein levels of HBx by Western blot. The half-life of HBx in the transfected cells treated with cycloheximide (CHX) were detected. The phosphorylation assay was used to evaluate the effects of PP4C on HBx phosphorylation. CCK8 assay, wound healing assay and Matrigel invasion chamber assay were used to analyze the effects of PP4C on the biological functions of HBx. Results:PP4C interacted with HBx in vivo and in vitro. PP4C overexpression significantly increased the protein level and stability of HBx and the phosphorylation assay confirmed that PP4C overexpression decreased the serine phosphorylation of HBx in hepatoma cells. PP4C overexpression enhanced the migration and invasion of hepatoma cells, but had no significant effects on the proliferation. Conclusions:The interactions between HBx and PP4C promoted the stability of HBx and ultimately enhanced the migration and invasion of hepatoma cells, and the mechanisms might be related to the decrease of HBx serine phosphorylation by PP4C. This study provided a theoretical basis for further investigation of the pathogenic mechanisms of HBx, and targeting PP4C and HBx interaction might provide insights for developing novel treatment for HBV-related hepatocellular carcinoma.

Advances of aerobic glycolysis in renal interstitial fibrosis / 中华肾脏病杂志

Aerobic glycolysis is a metabolic process in which cellular energy production favors the low-efficiency energy-producing glycolytic pathway in the presence of sufficient oxygen, reducing dependence on aerobic respiration, while producing energy rapidly and providing advantages for cell survival and proliferation. In recent years, several studies have shown that aerobic glycolysis is involved in the development of renal interstitial fibrosis (RIF) and involves various cell types such as fibroblasts, endothelial cells, renal tubular epithelial cells, pericytes, and inflammatory cells. Drugs targeting glycolysis may provide new ideas for the prevention and treatment of RIF. This article reviews the research progress of abnormal aerobic glycolysis in different cells and glycolytic intervention drugs in RIF.

One case of myeloid sarcoma with multiple space occupying lesions in the spinal canal / 中华神经科杂志

Myeloid sarcoma (MS) is a tumor mass formed by the proliferation of one or more myeloid primitive cells outside the marrow, which is mostly related to acute myeloid leukemia (AML). It is reported that 2.5% to 9.1% of AML patients have MS, and AML with spinal canal MS is very rare. Spinal canal MS often has an acute onset and is difficult to diagnose. It is easy to cause missed diagnosis and misdiagnosis, which will lead to a delay in accurate diagnosis seriously affecting the treatment and quality of life among these patients. The clinical data, diagnosis and treatment process of a case of MS with multiple space occupying lesions in the spinal canal diagnosed and treated by the Department of Hematology of Peking Union Medical College Hospital are reported, in order to provide reference for clinical workers.

The roles and clinical controversies of radiotherapy and immunotherapy in abscopal effect / 中华放射肿瘤学杂志

As early as the 20 th century, it has been observed that radiotherapy (RT), as a local therapy, can activate the adaptive immune system, resulting in spontaneous regression of tumors out of the radiation field, which is known as "abscopal effect". Although the occurrence of abscopal effect is still rare, with the gradual increase in the application of immunotherapy, more and more clinical cases of abscopal effect have been reported. Increasing attention has been paid to the therapeutic potential of RT in inducing systemic anti-tumor response. Especially, the combination of RT and immunotherapy enhances the research value of abscopal effect. However, its mechanism has not been fully elucidated, and the optimal timing, dose and fractionation of RT are also under study. How to classify the beneficiary groups is also a key issue. In this article, the history of abscopal effect, and the role of RT and immunotherapy in this phenomenon were briefly introduced, and the existing controversies in clinical application were illustrated, aiming to clarify the direction of current research and development and open a new chapter for tumor treatment in a short period of time.

Detection rate and clinical characteristics of vulvar squamous intraepithelial lesion / 中华妇产科杂志

Objective:To explore the detection rate, clinical characteristics of vulvar squamous intraepithelial lesion (SIL).Methods:Women diagnosed with vulvar high-grade squamous intraepithelial lesions (HSIL) through colposcopy-guided biopsy from January 1, 2018 to August 31, 2022 in Obstetrics and Gynecology Hospital of Fudan University were included in a 1∶1 ratio with patients diagnosed with vulvar low-grade squamous intraepithelial lesions (LSIL) during the same period. Clinical characteristics including human papillomavirus (HPV) infection rate, genotype, cytology result, colposcopy impression, and lesion location were retrospectively analyzed.Results:(1) The proportion of vulvar SIL detected by colposcopy-guided biopsy increased annually from 2018 to 2022, with rates of 1.64% (740/45 057), 2.34% (1 110/47 402), 2.68% (1 108/41 335), 3.26% (1 536/47 078), 3.31% (667/20 155), with an average rate of 2.57% (5 161/201 027). (2) A total of 1 096 cases of vulvar HSIL and 1 096 cases of vulvar LSIL were included. The overall infection rate of HPV was 92.7% (1 993/2 150), with higher infection rate in vulvar HSIL patients than that in vulvar LSIL patients [96.0% (1 012/1 054) vs 89.5% (981/1 096); χ2=33.62, P<0.001]. Among vulvar HSIL patients, the common HPV genotype from high to low were HPV 16 (66.7%), HPV 52 (14.3%), and HPV 58 (10.0%). For vulvar LSIL patients, the most common HPV genotype were respectively HPV 16 (24.9%), HPV 6 (20.1%) and HPV 52 (17.1%). The overall sensitivity rate of cytology was 53.6%, with no significance difference between vulvar LSIL and HSIL groups (54.3% vs 52.9%; χ2=0.40, P=0.526). The accuracy of colposcopy impression for vulvar HSIL was lower than that for vulvar LSIL [40.2% (163/405) vs 81.7% (380/465); χ2=158.72, P<0.001]. About 57.3% (1 257/2 192) of the patients had concomitant cervical and vaginal lesions, with a higher rate in vulvar HSIL group than that in vulvar LSIL group [62.6% (686/1 096) vs 52.1% (571/1 096); χ2=24.67, P<0.001]. Unifocal lesion was the main type, with no significance difference between vulvar LSIL and HSIL groups [81.4% (381/468) vs 82.5% (386/468); χ2=0.18, P=0.671]. The most common lesion locations were the posterior commissure, followed by labia minora, vaginal vestibule, labia majora, perianal and clitoris. Conclusions:The detection rate of vulvar SIL under colposcopy is about 3%, and the infection rate of HPV is 92.7%. Vulvar SIL, especially vulvar HSIL, is likely to cause concomitant cervical and vaginal lesions. The accuracy of colposcopy in diagnosing vulvar HSIL is low. Therefore a comprehensive and careful examination of the vulva is necessary and suspicious vulvar lesions should be undergone colposcopy-guided biopsy for diagnosis.

Effect of diosmetin on ferroptosis of hippocampal cells in rats with bacterial meningitis and the mechanism of SIRT1-Nrf2 signaling pathway / 中华行为医学与脑科学杂志

Objective:To explore the effect and mechanism of diosmetin (Dio) on neuronal ferroptosis in rats with bacterial meningitis (BM).Methods:Male SD rats aged 6-7 weeks of SPF grade were selected for the experiment. The BM model was established by injecting group B hemolytic streptococcus into the cisterna magna of cerebellum. Sixty BM model rats were successfully modeled and divided into model group, low-dose Dio group, medium-dose Dio group, high-dose Dio group and inhibitor group according to the random number table method, with 12 rats in each group. Another 12 weight-matched rats were taken as the control group.The rats in the low-dose Dio group, medium-dose Dio group, high-dose Dio group and the inhibitor group were intragastrically administered with Dio at 50 mg/kg, 100 mg/kg, 200 mg/kg and 200 mg/kg, respectively. The rats in the control group were intragastrically administered with an equal volume of 0.9 % sodium chloride solution. On the day of intragastric administration, the rats in the inhibitor group were intraperitoneally injected with SIRT1 pathway inhibitor EX527 (10 mg/kg), and the rats in the other groups were injected with an equal volume of 0.9% sodium chloride solution. The above interventions were performed once a day for 28 consecutive days. Loeffler neurological score was used to evaluate the neurological impairment in rats. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cerebrospinal fluid of rats were detected by ELISA. The number of white blood cells in cerebrospinal fluid was detected by a blood cell analyzer. Glutathione (GSH) was detected by micro-enzyme labeling method, malondialdehyde (MDA) was detected by thiobarbituric acid colorimetric method, reactive oxygen species(ROS) was detected by colorimetry, and Fe 2+ level was detected by ferrozine method. Hematoxylin-eosin staining, Prussian blue staining and TUNEL staining were used to observe the pathological damage, iron accumulation and apoptosis in the hippocampus, respectively.Western blot was applied to measure the expression of transferrin (Tf), proliferating cell nuclear antigen (PCNA), Bcl-2-associated X protein (Bax), caspase-3 and SIRT1/Nrf2/HO-1/Gpx4 signaling pathway proteins. Graphpad Prism 9.0 was used for data analysis. One-way ANOVA was used for statistical analysis, and SNK- q test was used for further pairwise comparisons. Results:(1) There was a statistically significant difference in neurological function scores among the 6 groups of rats ( F=125.451, P<0.001). The neurological function score of the model group was lower than that of control group, while the neurological function scores of the low-dose Dio group, medium-dose Dio group, and high-dose Dio group were higher than those of the model group (all P<0.05). The neurological function score of the inhibitor group ((2.57±0.26)) was lower than that of high-dose Dio group ((4.34±0.48)) ( P<0.05). (2) There were statistically significant differences in the levels of IL-6, TNF-α and the number of white blood cells in the cerebrospinal fluid of rats among the 6 groups ( F=127.817, 102.413, 180.967, all P<0.001). The levels of IL-6, TNF-α and the number of white blood cells in model group were higher than those of control group(all P<0.05). The levels of IL-6, TNF-α and the number of white blood cells in low-dose Dio group, medium-dose Dio group and high-dose Dio group were lower than those of model group (all P<0.001), and those in inhibitor group were all higher than those in high-dose Dio group(all P<0.001). (3) There were statistically significant differences in iron deposition rate and neuronal apoptosis rate among the 6 groups of rats ( F=90.857, 88.835, both P<0.001). The iron deposition rate ((18.37±3.14)%) and neuronal apoptosis rate ((27.58±2.63)%) in the inhibitor group were higher than those in the high-dose Dio group ((6.35±1.08)%, (14.02±1.87)%) (both P<0.05). (4) The levels of GSH, ROS, MDA, and Fe 2+ in the hippocampus of the 6 groups of rats showed statistically significant differences ( F=54.465, 106.453, 55.969, 105.457, all P<0.001). The GSH content in the inhibitor group ((103.48±8.76) mmol/g) was lower than that in the high-dose Dio group ((133.97±10.54) mmol/g), while the contents of ROS, MDA, Fe 2+ ((225.17±16.32) μmol/mg, (10.73±1.58) μmol/mg, (62.71±5.43) μg/g) were higher than those of the high-dose Dio group ((131.87±11.67) μmol/mg, (4.35±0.87) μmol/mg, (34.86±2.95) μg/g) (all P<0.05). (5)There were statistically significant differences in the protein levels of Tf, PCNA, Bax, caspase-3, SIRT1, Nrf2, HO-1 and Gpx4 in the hippocampus of the 6 groups of rats ( F=120.179, 107.568, 157.265, 98.031, 90.932, 52.283, 59.424, 114.539, all P<0.001). The protein levels of Tf, Bax and caspase-3 in the hippocampus of inhibitor group were higher than those of the high-dose Dio group, while the protein levels of PCNA, SIRT1, Nrf2, HO-1, Gpx4 were lower than those of the high-dose Dio group (all P<0.05). Conclusion:Diosmetin can activate SIRT1/Nrf2/HO-1/Gpx4 signaling pathway, thereby inhibiting neuronal ferroptosis in BM rats.