To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

Objective To discover new-structure active molecules in order to provide candidate compounds for anti-radiation drug research.Methods Conformational fixation and functional group conversion strategies were used to modify the structure of Ex-RAD before substituted 2H-benzopyran-3-formylaniline compounds were designed and synthesized.The anti-radiation activities of the synthesized compounds were screened via irradiated cell survival models and the cytotoxicity of the active compounds was examined.Western blotting assay was used to investigate the effects of the optimal compound on the expressions of apoptosis related proteins in irradiated cells.The anti-radiation activity of the optimal compound was evaluated through irradiated mice models.Results Twenty-one target compounds were synthesized,eight of which were found to significantly improve the survival of irradiated cells.Four compounds were selected for re-screening and cytotoxicity evaluation.Compound D19 was determined as the optimal compound that could affect the expressions of apoptosis related proteins in irradiated AHH-1 cells by Western blotting assay.Compared with the radiation group,the 30-day survival rate of D19 treated mice irradiated with 8.6 Gy of whole-body radiation increased by 70%.D19 showed protective effect on the blood system of non-lethal dose irradiated mice.Conclusion The novel compound D19 has shown strong anti-radiation activity and deserves more research.

Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Objective:To analyze the exposure level and changes in severe respiratory infection among Chinese residents aged ≥40 years in China and to provide essential data for preventing and controlling chronic respiratory diseases.Methods:The data came from chronic obstructive pulmonary disease surveillance of Chinese residents in 2014-2015 and 2019-2020. The surveillance covers 31 provinces (autonomous regions and municipalities) in China. A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥40 years. Relevant information about exposure to severe respiratory infections during childhood was collected through investigation. Rigorous complex sampling and weighted analysis were applied to estimate the exposure rate of severe respiratory infections among children with different characteristics among residents aged ≥40 years in China from 2019 to 2020. Additionally, changes in severe respiratory infections during childhood were analyzed over 2014-2015 and 2019-2020.Results:In 2019-2020, the exposure rate of severe respiratory infection before 18 for residents aged ≥40 years in China was 21.58‰ (95% CI: 17.57‰-25.59‰). The exposure rate of severe respiratory infection before the age of 14 was 19.40‰ (95% CI:15.25‰-23.55‰), the difference in the exposure rate between men and women was not statistically significant (both P>0.05), and the exposure rate of urban residents is higher than that of rural residents. The results of multivariate logistic regression analysis showed that in western rural areas, factors including being born by cesarean section, exposure to secondhand smoke before age 14 years old, and a family history of chronic respiratory diseases were associated with severe respiratory infections in childhood. Compared with 2014-2015, the proportion of residents aged 40 and older in China hospitalized for pneumonia or bronchitis before 14 from 2019 to 2020 was slightly lower than five years prior. Conclusions:Among residents in China aged ≥40 years, 21.58‰ experienced severe respiratory infection exposure during childhood, varying exposure levels across different demographic groups. The burden of chronic respiratory diseases in adulthood cannot be ignored. Efforts should be made to expand the coverage of planned immunization and to focus on early-life interventions during childhood to reduce the incidence of severe respiratory infections.

Ebola virus (EBOV) is an enveloped negative-sense RNA virus and a member of the filovirus family. Nucleoprotein (NP) expression alone leads to the formation of inclusion bodies (IBs), which are critical for viral RNA synthesis. The matrix protein, VP40, not only plays a critical role in virus assembly/budding, but also can regulate transcription and replication of the viral genome. However, the molecular mechanism by which VP40 regulates viral RNA synthesis and virion assembly/budding is unknown. Here, we show that within IBs the N-terminus of NP recruits VP40 and is required for VLP-containing NP release. Furthermore, we find four point mutations (L692A, P697A, P698A and W699A) within the C-terminal hydrophobic core of NP result in a stronger VP40-NP interaction within IBs, sequestering VP40 within IBs, reducing VP40-VLP egress, abolishing the incorporation of NC-like structures into VP40-VLP, and inhibiting viral RNA synthesis, suggesting that the interaction of N-terminus of NP with VP40 induces a conformational change in the C-terminus of NP. Consequently, the C-terminal hydrophobic core of NP is exposed and binds VP40, thereby inhibiting RNA synthesis and initiating virion assembly/budding.
Ebolavirus/physiology* ; HEK293 Cells ; HeLa Cells ; Humans ; Nucleocapsid Proteins/metabolism* ; RNA, Viral/metabolism* ; Viral Matrix Proteins/metabolism* ; Virion/metabolism* ; Virus Assembly

AIM: To study the protective effect and mechanism of swimming on kidney of diabetic mice. METHODS: The mice were randomly divided into normal control group, normal swimming group, type 2 diabetes mellitus (T2DM) mice model group, diabetic swimming group and metformin group. T2DM model was established by streptozotocin (STZ) method. The mice in normal swimming group and diabetic swimming group were given swimming exercise (1 h a day), and the metformin group were given metformin (200 mg/kg) by gavage once a day for 7 weeks. Fasting blood glucose and serum insulin were measured and insulin resistance index was calculated. The contents of uric acid, urea and creatinine in serum were determined. The ratio of renal mass to body mass was calculated, and the pathological changes of renal tissues were observed. The relative expressions of autophagy related proteins LC3 and P62 in renal tissues were detected by Western blot. RESULTS: Compared with normal control group, insulin resistance index and renal mass/body mass ratio in model group were significantly increased. Serum uric acid, urea and creatinine levels increased, and glomerular pathological changes were obvious. LC3II/LC3I ratio decreased significantly. The expression of P62 was significantly increased. Compared with model group, insulin resistance index and renal mass/body mass ratio in diabetic swimming group were significantly decreased. The contents of serum uric acid, urea and creatinine decreased, and the pathological changes of glomerular were alleviated. LC3II/LC3I ratio increased significantly. The expression of P62 decreased significantly (P even <0.05). CONCLUSION: Swimming protects the kidney injury of T2DM mice, and its mechanism may be related to promoting the autophagy process of renal tissue.

ObjectiveTo explore the effective components， targets， and mechanism of Houttuynia cordata against lung cancer by means of systems pharmacology and further to provide a reference for the further development and clinical application of this medicinal. MethodChemical components of H. cordata were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the active components were screened based on oral bioavailability （OB） and drug-likeness （DL）. Then the potential targets were predicted， followed by enrichment analysis. Finally， sodium houttuyfonate （SH） was selected for verifying the anti-tumor mechanism. Cell counting kit-8 （CCK-8） assay was used to evaluate the effect of SH on the in vitro proliferation of two lung cancer cell lines： A549 and LLC， and the regulation of tumor-related proteins by SH was verified by Western blot. ResultA total of 7 active compounds and 352 targets of the active components were screened out. According to the enrichment analysis of targets， H. cordata had potential therapeutic effects on cancer. SH had inhibitory effect on both A549 and LLC. Western blot results showed that G₁/S-specific Cyclin D₁， E₁ and cyclin-dependent kinase （CDK）2， CDK4 all tended to be down-regulated， and Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） also changed significantly. ConclusionH. cordata has the potential anti-tumor effects by arresting the tumor cells in the G₁ phase through the JAK2/STAT3 pathway.

Background and Objectives: Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity，and VEC (vascular endothelial cell) differentiation in vitro, we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis. Methods: and Results: We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p＜0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3. Conclusions We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.

Objective: To explore the effect of high mobility group box-1 protein (HMGB1) on the balance of Th17/Treg in patients with immune thrombocytopenia (ITP). Methods: A total of 30 patients who were first diagnosed as ITP in the Fifth People's Hospital of Datong from July 2017 to April 2018 were selected as the case group, and another 30 healthy volunteers in the corresponding period were taken as the control group. The proportion of Th17 and Treg cells was detected by using flow cytometry, and the concentration of HMGB1, interleukin (IL)-17 and transforming growth factor β (TGF-β) in plasma was tested by using enzyme-linked immunosorbent assay (ELISA). Isolated peripheral blood mononuclear cells (PBMC) were cultured in vitro. After the treatment with recombinant human HMGB1 (rhHMGB1), real-time polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression changes in Treg cell transcription factor intracellular forkhead helix transcription factor 3 (Foxp3) and Th17 cell transcription factor retinoid related orphan receptor γt (RORγt). The differences of indicators in Treg cell transcription factor peripheral blood between the case group and the control group were compared, and the balance correlation between HMGB1 and Th17/Treg was analyzed. Results: Compared with the healthy control group, the proportion of Th17 cells and the expression level of HMGB1 and IL-17 in peripheral blood of ITP patients were increased (all P < 0.01), while the proportion of Treg cells and the level of TGF-β were decreased (all P < 0.01). The proportion of Th17 cells and the expression level of IL-17 and HMGB1 in peripheral blood of ITP patients were positively correlated with the concentration of HMGB1 (all P < 0.01); the proportion of Treg cells and the level of TGF-β were negatively correlated with the expression level of HMGB1 (all P < 0.01). In vitro experiments, the expression of intracellular RORγt mRNA was increased compared with the negative control group (1.50±0.24 vs. 0.93±0.22, t = 9.612, P < 0.01), and the expression of Foxp3 mRNA was decreased compared with the negative control group after the stimulation of PBMC by rhHMGB1 (0.72±0.19 vs. 1.08±0.18, t = 7.387, P < 0.01). Conclusion The high level of HMGB1 in the peripheral blood of ITP patients induces Th17/Treg imbalance and aggravates inflammatory reactions, which may be an important cause of ITP.

Objective:To explore the influencing factors of uterine myometrial and parauterine venous plexus reflux during transvaginal four-dimensional contrast-enhanced hysterosalpingography, which will help reduce and avoid the occurrence of reflux and improve the accuracy of diagnosis.Methods:A total of 306 infertile patients who underwent transvaginal four-dimensional contrast-enhanced hysterosalpingograph from June 2016 to June 2017 in the Third Affiliated Hospital of Guangzhou Medical University were retrospectively enrolled. The ultrasonographic characteristics were reviewed and the correlations between reflux and endometrial thickness, days after menstruation, intrauterine operation history and patency of fallopian tube were analyzed.Results:The incidence of countercurrent during four-dimensional contrast-enhanced hysterosalpingography was 14.71%. The chi-square test showed that the endometrial thickness and the days after menstruation had statistically significant effects on the incidence of reflux ( P=0.031 and <0.001, respectively). There were no statistically significant effects of intrauterine operation history and patency of the fallopian tube on the incidence of reflux ( P=0.610, 0.137). Logistic regression analysis showed that the incidence of reflux was associated with endometrial thickness ( B=-1.171, P<0.001) and the days after menstruation ( B=0.439, P=0.015). Conclusions:Transvaginal ultrasound measurement of endometrial thickness before angiography and selection of appropriate examination time according to the menstrual cycle can effectively reduce the incidence of reflux, and adverse reactions, and improve the accuracy of four-dimensional contrast-enhanced hysterosalpingography.