Prognostic Value and Immune Infiltration of Anoikis-related LncRNAs in Lung Adenocarcinoma / 肿瘤防治研究

Objective To explore the prognostic value and immune infiltration landscape of anoikis-related long noncoding RNAs (arlncRNAs) in lung adenocarcinoma. Methods RNA-seq and clinical data of lung adenocarcinoma were downloaded from the TCGA database, and anoikis-related genes were obtained from the GeneCards and Harmonizome databases. Coexpression, differential, and WGCNA analyses were performed to screen differentially expressed arlncRNAs closely related to the occurrence of lung adenocarcinoma. A prognostic risk model was then constructed based on the arlncRNAs, and its predictive efficacy was further validated. Finally, consensus clustering was used to identify the molecular subtypes associated with anoikis in lung adenocarcinoma. Results Seven prognostic arlncRNAs were identified, and the prognostic risk models established based on them had AUC values of ROC curves greater than 0.7. Survival and immune infiltration analyses revealed that low-risk patients had high overall survival and immune infiltration, implying that they experienced good immune treatment effects. Drug sensitivity analysis showed that the high-risk patients were more sensitive to commonly used chemotherapeutic agents than the low-risk patients. According to the expression of model genes, subtypes C1 and C2 were identified through consensus clustering, and C1 showed a good prognosis. Conclusion The prognostic risk model based on the seven arlncRNAs can effectively predict the prognosis of lung adenocarcinoma patients. The results of immune-related and drug sensitivity analyses provide a reference for the precise individualized treatment of patients with lung adenocarcinoma.

The relationship between mean daily step counts and pulmonary complications after thoracoscopic lobectomy in elderly patients: A propensity score matching study / 中国胸心血管外科临床杂志

@#Objective     To investigate the relationship between preoperative mean daily step counts and pulmonary complications after thoracoscopic lobectomy in elderly patients. Methods     From 2018 to 2021, the elderly patients with pulmonary complications after thoracoscopic lobectomy were included. A 1∶1 propensity score matching was performed with patients without pulmonary complications. The clinical data were compared between the two groups. Results    Totally, 100 elderly patients with pulmonary complications were enrolled, including 78 males and 22 females, aged 66.4±4.5 years. And 100 patients without pulmonary complications were matched, including 71 males and 29 females aged 66.2±5.0 years. There was no significant difference in the preoperative data between the two groups (P>0.05). Compared to the patients with pulmonary complications, the ICU stay was shorter (8.1±4.4 h vs. 12.9±7.5 h, P<0.001), the first out-of-bed activity time was earlier (8.8±4.5 h vs. 11.2±6.1 h, P=0.002), and the tube incubation time was shorter (19.3±9.2 h vs. 22.5±9.4 h, P=0.015) in the patients wihout pulmonary complications. There was no statistical difference in other perioperative data between the two groups (P>0.05). The mean daily step counts in the pulmonary complications group were significantly less than that in the non-pulmonary complications group (4 745.5±2 190.9 steps vs. 6 821.1± 2 542.0 steps, P<0.001). The daily step counts showed an upward trend for three consecutive days in the two groups, but the difference was not significant. Conclusion     The decline of preoperative mean daily step counts is related to pulmonary complications after thoracoscopic lobectomy in elderly patients. Recording daily step counts can promote preoperative active exercise training for hospitalized patients.

Research progress on 577 nm subthreshold micropulse laser for retinal diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Laser photocoagulation is one of the important methods for treating retinal diseases, and retinal laser technology continues to advance. For decades, researchers have been striving to find a laser treatment that can minimize tissue damage while achieving optimal results. With low toxicity, low scattering light, strong penetrating power, small compared with the traditional laser damage, light reaction and no pain, the 577 nm subthreshold micropulse laser(SML)turns this goal into reality and ushers in a new era of laser treatment for fundus diseases. This article reviews the concept, mechanism, related parameters and clinical application progress of 577 nm SML in a variety of retinal diseases, aiming to provide references for clinical treatments.

Recommendations from Annals of Surgical Oncology： Clinical guidelines for extrahepatic cholangiocarcinoma and gallbladder carcinoma / 临床肝胆病杂志

Biliary tract carcinoma （BTC） is a type of gastrointestinal tumor with a low incidence rate and a strong invasive ability， mainly including intrahepatic cholangiocarcinoma （ICC）， extrahepatic cholangiocarcinoma （ECC）， and gallbladder carcinoma （GC）， often accompanied by local progression or distant metastasis. Surgery is often the preferred treatment method for patients with local resectable tumor； however， there is still a high risk of recurrence after radical surgery. Therefore， multiple treatment modalities are often required for BTC patients， including surgical resection， systemic treatment （such as targeted therapy， chemotherapy， and immunotherapy）， and/or a combination of local treatment methods. With the development of the field of BTC， it is critical for surgical oncologists to understand and master the latest surgical strategies and the best patient selection and management systems. In view of the complexity of treatment and the continuous development of diagnosis and treatment techniques， Annals of Surgical Oncology， an authoritative American journal of cancer surgery， recently published the practical diagnosis and treatment guidelines for hepatobiliary tumors， including hepatocellular carcinoma （HCC）， ICC， ECC， and GC， aiming to provide more evidence-based evidence for the clinical management and decision-making of patients with hepatobiliary tumors. Due to the limitations of length and different emphases， this article mainly introduces the recommendations for the evaluation points and clinical treatment of ECC and GC in the guidelines， so as to provide a reference for clinical practice.

Development and validation of a method for quantitation of cefepime/avibactam in M-H broth: application to antibacterial activity using in vitro PK/PD Model / 中国临床药理学与治疗学

AIM: To establish a method for quantitation of cefepime and avibactam in M-H broth, and applicated in the in vitro dynamic PK/PD model. METHODS: The cefepime was also determined using the high-performance liquid chromatography method (HPLC), the avibactam was also determined using the liquid chromatography-mass spectrometry (LC-MS/MS), an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae (CRKP). RESULTS: The linear ranges of cefepime and avibactam were good at (0.5-20) and (0.1-25) μg/mL (r=0.999), and the lower limit concentrations were 0.5 and 0.1 μg/mL. The extraction recoveries of cefepime and avibactam in M-H broth were 88.0%-101.7% and 90.9%-95.2%, the relative standard deviation of intra-day precision and inter-day precision were less than 5.2%. The concentration-time curves were well simulated by the PK/PD model. All observed concentrations in each experiment were in the range of 20% of the targeted values. For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL, the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mL at the cefepime/avibactam 2.5 g q8 h administration after 24 h. CONCLUSION: The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability. For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.

Association of polycyclic aromatic hydrocarbon metabolite concentration with sleep quality in workers / 环境与职业医学

Background Sleep is a crucial physiological activity for the human body, and research has shown that air pollution can affect sleep quality. However, the association between polycyclic aromatic hydrocarbons (PAHs) exposure, neurotoxic compounds in air pollutants, and sleep quality remains uncertain. Objective To evaluate the association of PAHs exposure with sleep quality, and to provide evidence for improving sleep quality. Methods This study used a cross-sectional design. We selected 632 workers from a coking plant of a large state-owned enterprise as the exposure group, and 477 workers from the energy and power plant of the same enterprise as the control group. All workers worked in three shifts. A questionnaire survey was conducted to collect basic information including gender, years of service, age, educational level, smoking, alcohol consumption, consumption of fried foods, cooking frequency, types of cooking fuels. Worker's post-shift morning midstream urine was sampled to determine the concentrations of eight PAHs metabolites (OH-PAHs) using gas chromatography-tandem mass spectrometry (GC-MS). Worker's sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI). A higher PSQI score indicated a lower sleep quality. Associations of urinary OH-PAHs levels with sleep quality in the workers were analyzed using linear regression, Bayesian kernel-machine regression (BKMR), and quantile g-computation. Results The median (P25, P75) concentration of total OH-PAHs in the exposure group [88.84 (46.27, 151.96) μg·L−1] was higher than that in the control group [54.33 (24.86, 97.97) μg·L−1]. Additionally, the PSQI score (\begin{document}$ \overline{x}\pm {s} $\end{document}) in the exposure group (5.16±3.84) was higher than that in the control group (4.60±3.17). The multiple linear regression revealed that an increase in the sum of the concentrations of eight OH-PAHs after natural logarithmic transformation (lnΣ8OH-PAHs) was associated with an increase of 0.3646 (95%CI: 0.1337, 0.5955) in PSQI score, and an increase in lnΣlow-ring OH-PAHs was associated with an increase of 0.2954 (95%CI: 0.0941, 0.4967) in PSQI score. The BKMR analysis demonstrated that PSQI score was gradually increased as the increasing of lnΣ8OH-PAHs concentration. The quantile g-computation analysis indicated that a quantile increase in lnΣ8OH-PAHs concentration was associated with an increase of 0.4062% (95%CI: 0.1176%, 0.6949%) in PSQI score. Conclusion Compared to the controls, the coking workers show a higher concentration of urinary OH-PAHs and report worse sleep quality. The concentration of OH-PAHs is significantly negatively associated with sleep quality.

Inhibition of Pannus Formation by Wutoutang in AIA Rats with Wind-cold-dampness Bi Syndrome Via Down-regulating HIF-1α/VEGFA/Ang Signaling Pathway / 中国实验方剂学杂志

ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis （AIA） rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free （SPF） rats were selected and divided into blank group， wind-cold-dampness Bi syndrome group ［Complete Freund's Adjuvant （CFA）， 200 μg］， Wutoutang group （15 g·kg-1·d-1）， and indometacin group （10 mg·kg-1） according to random number table method. Except for the blank group， the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days， the basic conditions， onset time， arthritis index score， and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally， peripheral arterial blood， ankle joint， and synovial tissue were taken. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum hypoxia-inducible factor-1α （HIF-1α）， vascular endothelial growth factor A （VEGFA） protein content， and rheumatism， including anti-O （ASO）， C-reactive protein （CRP）， and rheumatoid factor （RF）. Hematoxylin-eosin （HE） staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA， two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to reveal mRNA levels of HIF-1α， VEGFA， angiopoietin-1 （Ang-1）， and angiopoietin-2 （Ang-2） in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher （P<0.01） compared with the blank group. Serum CRP， RF， and ASO levels were considerably elevated （P<0.01）. HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation， angiogenesis and pannus formation， and aggravated bone destruction， indicating successful modeling. After the intervention of Wutoutang， the onset time was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. The inflammatory hyperplasia of synovial tissue， angiogenesis and pannus formation， and bone destruction were alleviated. The mRNA levels of HIF-1α， VEGFA， Ang-1， and Ang-2 in the synovial membrane were significantly decreased （P<0.05， P<0.01）. The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased （P<0.01）. In the indomethacin group， the onset time of the disease was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. HIF-1α/VEGFA/Ang signaling pathway was activated， and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome， reduce foot swelling volume， arthritis score， rheumatic activity， and improve joint histopathology. It can inhibit pannus formation， and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.

Efficacy of ursodeoxycholic acid in the prevention and treatment of COVID-19 in patients with chronic hepatitis B / 临床肝胆病杂志

ObjectiveTo investigate the potential effect of ursodeoxycholic acid （UDCA） in the prevention and treatment of COVID-19 in patients with chronic hepatitis B. MethodsClinical data were collected from 324 patients with chronic hepatitis B who were treated in Beijing Ditan Hospital， Capital Medical University， from January to December 2022， and according to whether UDCA was administered， they were divided into UDCA group and control group. The propensity score matching （PSM） method was used to balance the confounding factors such as age， sex， and chronic complications， and the two groups were compared in terms of SARS-CoV-2 infection rate， symptoms， and recovery time after COVID-19. The two groups were also compared in terms of related laboratory markers （white blood cell count ［WBC］， hemoglobin ［Hb］， platelet count ［PLT］， alanine aminotransferase ［ALT］， aspartate aminotransferase ［AST］， albumin ［Alb］， alkaline phosphatase ［ALP］， total bilirubin ［TBil］， triglyceride ［TG］， and total cholesterol ［TC］）， vaccination， and the incidence rate of liver disease symptoms after COVID-19. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of data with skewed distribution between the two groups； the chi-square test and the continuously corrected chi-square test were used for comparison of categorical data between two groups. The binary Logistic regression model was used for univariate and multivariate analyses to investigate the influencing factors for COVID-19 after matching. ResultsThere were 87 patients in the UDCA group and 237 patients in the control group， and after PSM， there were 78 patients in the UDCA group and 137 patients in the control group， with good balance between the two groups. There was a significant difference in SARS-CoV-2 infection rate between the UDCA group and the control group ［82.1% （64/78） vs 95.6% （131/137）， χ2=10.847， P=0.001］. After COVID-19， compared with the control group， the UDCA group had a significantly lower proportion of the patients with chill （10.9% vs 38.9%， χ2=16.124， P<0.001） and cough （56.3% vs 74.8%， χ2=6.889， P=0.009）. There was a significant difference between the UDCA group and the control group in the proportion of the patients with a recovery time of ≤7 days after COVID-19 （79.7% vs 61.1%， χ2=6.760， P=0.009）. Both univariate and multivariate logistic regression analyses showed that UDCA was an independent influencing factor for COVID-19 （odds ratio=0.21 and 0.17， both P<0.05）. ConclusionUDCA is an protective factor against COVID-19 in patients with chronic hepatitis B and can alleviate related symptoms to some extent and shorten the recovery time， and therefore， it has an important value in the prevention and treatment of COVID-19.

Clinical Observation on Rongjin Tongbi Decoction in Treating Sciatica Caused by Lumbar Intervertebral Disc Herniation with Liver and Kidney Deficiency Type / 中国实验方剂学杂志

ObjectiveTo evaluate the efficacy and safety of Rongjin Tongbi decoction on sciatica caused by lumbar intervertebral disc herniation with liver and kidney deficiency type based on a randomized controlled study. MethodFrom January 2019 to July 2022， 90 patients in the department of Traditional Chinese medicine（TCM） of Beijing Jishuitan Hospital who met the inclusion criteria were selected and divided into two groups according to the random number table， with 45 patients in each group. During the study， 19 cases dropped out， with 41 cases included in the final observation group and 30 cases in the control group. The observation group was given Rongjin Tongbi decoction orally， and the control group was given Loxoprofen Sodium Tablets orally for 28 days. The differences in the visual analog scale （VAS） scores， the Japanese Orthopaedic Association （JOA） scores， activities of daily living （ADL） assessments， TCM clinical symptoms， subjective symptoms， and clinical signs scores between two groups before and after treatment were observed. Liver and kidney functions and gastrointestinal adverse reactions were detected for safety evaluation. ResultBefore treatment， there was no statistically significant difference in scores between the observation group and the control group. After treatment， the absolute values of the differences in VAS and ADL scores in the observation group were higher than those in the control group （P<0.05）. There was no statistically significant difference in the absolute value of the difference in JOA scores between two groups. The absolute value of the difference in TCM clinical symptom scores in the observation group was higher than that in the control group （P<0.01）. There was no statistically significant difference in the absolute values of the differences in subjective symptom and clinical sign scores between two groups. The levels of liver and kidney function indicators in both groups before and after the experiment were normal， and there was no significant difference in gastrointestinal reactions. ConclusionRongjin Tongbi decoction can significantly improve the symptoms of sciatica patients caused by lumbar intervertebral disc herniation with liver and kidney deficiency type. After treatment， the patients exhibited significant improvements in pain， activity and other aspects， and it is proven to be safe and reliable， which is conducive to the recovery of physical function.

Analysis of associated factors of attempting e-cigarettes use among senior high school students in Beijing City between 2019 and 2023 / 中国学校卫生

Objective@#To analyze prevalence and associated factors of attempting e cigarettes use among senior high school students in Beijing City between 2019 and 2023, in order to providing references for the construction of smoke free senior high schools environments.@*Methods@#In 2019, 9 137 students from 44 senior high schools in Beijing City were monitored, including 27 general senior high schools and 17 vocational senior high schools. In 2023, the study included 6 709 students from 30 senior high schools comprising 21 general senior high schools and 9 vocational senior high schools. On site investigations using anonymous questionnaires were conducted. The monitoring content included demographic information, second hand smoke exposure, tobacco product use and tobacco awareness. Chi square test was used to compare the differences of various indicators in different groups, and multivariate Logistic regression analysis was adopted to analysis the influencing factors among senior high school students attempting to use e cigarettes between 2019 and 2023.@*Results@#In 2019, the rates of vocational senior high school and general senior high school students attempting to use e-cigarettes were 22.57% and 9.78%, respectively. In 2023, it decreased to 14.39% and 6.43%, respectively. In 2019 ( OR =1.59,95% CI =1.35-1.88) and 2023 ( OR =1.71,95% CI =1.38-2.11), vocational senior high school students both hold higher risk of attempting to use e-cigarettes,compared with general senior high school students. In 2019, non-indigenous senior high school students attempting to use e cigarettes were more than indigenous senior high school students ( OR = 1.28 , 95% CI =1.05-1.56). In 2019 ( OR =1.62, 95% CI =1.34-1.95) and 2023 ( OR =1.77, 95% CI =1.35-2.31), smoking anywhere in households increased the risk of attempting to use e-cigarettes among senior high school students. In both 2019 and 2023, not attempting to smoke cigarettes ( OR =0.24,95% CI =0.21-0.29; OR =0.15,95% CI =0.11-0.19), not currently smoking cigarettes ( OR =0.29,95% CI =0.22-0.40; OR =0.30,95% CI =0.17-0.53), not being exposed to secondhand smoke in school ( OR =0.62, 95% CI = 0.53 -0.72; OR =0.51, 95% CI =0.41-0.64) or in outdoor public places ( OR =0.74, 95% CI =0.63-0.86; OR = 0.62 , 95% CI =0.50-0.78) all reduced the risk of attempting to use e-cigarettes among senior hgih school students( P <0.05).@*Conclusion@#The influencing factors of attempts by senior high school students in Beijing City to use e-cigarettes are generally consistent between 2023 and 2019, with a focus on vocational senior high schools to ensure the continuity of intervention measures and promote the construction of smoke free senior high schools.

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes / 中国结合医学杂志

OBJECTIVE@#To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.@*METHODS@#Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.@*RESULTS@#TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).@*CONCLUSIONS@#TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

Searching for Novel Candidate Small Molecules for Ameliorating Idiopathic Pulmonary Fibrosis: a Narrative Review

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)-β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

Investigation on the pharmacological mechanisms of Shirebi granules in treating gouty arthritis with damp-heat syndrome based on crosstalk of Wnt/β-catenin signaling / 药学学报

Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).

Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping / 药学学报

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Mechanism of Dahuang Zhechongwan in Inhibiting Renal Fibrosis in Rats by Regulating Intestinal Flora Based on 16S rDNA Sequencing / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Dahuang Zhechongwan （DHZCW） on adenine-induced renal fibrosis in rats from the perspective of intestinal flora. MethodThirty-six SD rats were randomly divided into a blank group， a model group， and high-， medium- and low-dose DHZCW groups （0.168， 0.084， 0.042 g·kg-1）， and a pirfenidone group （200 mg·kg-1）， with 6 rats in each group. Except for those in the blank group， rats in other groups were treated with adenine suspension （250 mg·kg-1） by gavage for 28 days for renal fibrosis model induction. Subsequently， they received drug intervention for 4 weeks. Urine samples were collected from rats in metabolic cages， and renal function indicators including blood urea nitrogen （BUN）， urea， creatinine （Crea）， cystatin C （Cys C）， and 24-hour urine protein （24 h TP） were measured. Kidney samples were collected and subjected to hematoxylin-eosin （HE） staining and Masson's trichrome staining to observe the pathological changes in rat renal tissues. Western blot was used to detect the expression levels of key effector proteins α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， and type Ⅲ collagen （ColⅢ） in the kidneys. High-throughput sequencing of 16S rDNA was used to analyze the species diversity of rat intestinal flora. ResultCompared with the blank group， the model group showed increased BUN， urea， Crea， Cys C， and 24 h TP levels （P<0.01）. Compared with the model group， the high-， medium-， and low-dose DHZCW groups， as well as the pirfenidone group， showed significant reductions in BUN， urea， Crea， Cys C， and 24 h TP levels （P<0.01）， indicating that DHZCW intervention significantly improved renal function. In the model group， renal tissues exhibited significant fibrotic changes， and the protein levels of α-SMA， ColⅠ， and ColⅢ were significantly increased （P<0.01） compared to those in the blank group. Compared with the model group， the high-dose DHZCW group and the pirfenidone group had relatively normal tissue structure， with no significant pathological damage observed. However， fibrotic changes were observed in the medium- and low-dose DHZCW groups， with the changes being more significant in the low-dose group. The protein levels of α-SMA， ColⅠ， and ColⅢ were significantly decreased in the high-， medium-， and low-dose DHZCW groups， as well as the pirfenidone group （P<0.01）， indicating that DHZCW effectively reduced abnormal collagen deposition and inhibited renal fibrosis. From the perspective of intestinal flora， at the phylum level， compared with the blank group， the model group showed a significant increase in the abundance of Firmicutes and a decrease in Bacteroidetes， leading to a significant imbalance in their ratio. At the family level， the model group decreased the abundance of Lachnospiraceae， Prevotellaceae， and Bacteroidota_unclassified， and increased the abundance of Ruminococcaceae， Lactobacillaceae， and Oscillospiraceae. At the genus level， the model group showed significantly reduced abundance of Firmicutes_unclassified， Bacteroidota_unclassified， and Prevotellaceae_UCG-001， etc.， and increased abundance of UCG-005， Clostridia_UCG-014_unclassified， etc. Compared with the model group， DHZCW effectively reduced the abundance of potential pathogenic bacteria and increased the abundance of beneficial bacteria， regulating the intestinal flora. ConclusionDHZCW can effectively improve renal function and inhibit renal fibrosis， and its mechanism of action may be related to the regulation of intestinal flora.

Surgical versus conservative treatment for acute type A aortic intramural hematoma: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To compare the outcomes following emergency surgery or conservative treatment for patients with acute type A aortic intramural hematoma (IMH). Methods    Clinical data of consecutive patients diagnosed with acute type A aortic IMH in our hospital from September 2014 to December 2018 were retrospectively analyzed. The patients who met our surgical indications received surgery (an operation group) and other patients received strict conservative treatment (a conservative treatment group). Results    Finally 127 patients were enrolled, including 112 males and 15 females with an average age of 53.6±13.0 years. Of 127 patients, 85 (66.9%) patients accepted emergency surgery and 42 (33.1%) patients accepted strict conservative treatment. There was no difference between the two groups in early mortality or complications (P>0.05). The 5-year survival rate was 90.4% in the operation group and 74.3% in the conservative treatment group (P=0.010). A maximum aortic diameter in the ascending aorta and aortic arch≥45 mm and maximum thickness of IMH in the same section≥8 mm were risk factors for IMH-related death in patients undergoing conservative treatment (P<0.001). Conclusion    The mortality associated with emergency surgery for patients with acute type A aortic IMH is satisfactory. In clinical centers with well-established surgical techniques and postoperative management, emergency surgical treatment may provide a better outcome than conservative treatment for patients with acute type A aortic IMH.

Metabolic regulation of Nod-like receptor protein 3 inflammasome and its role in renal diseases / 中华肾脏病杂志

In recent years, with the development of metabolic reprogramming research, people have changed their understanding of the biological effects of immune cells. Under the stimulation of inflammatory response, immune cells re-regulate their metabolism and bioenergetics, provide energy and substrates for cell survival, and initiate immune effect functions. Nod-like receptor protein 3 (NLRP3) inflammasome, as an important component of the innate immune system, has been shown to sense metabolites such as uric acid and cholesterol crystals, and can be inhibited by metabolites such as ketones. It is also regulated by mitochondrial reactive oxygen species and glycolytic components (such as hexokinase). Recent studies have shown that a variety of metabolic pathways converge as effective regulators of NLRP3 inflammasome. The paper reviews the metabolic regulatory pathways and specificity of NLRP3 inflammasome activation, and its role in renal diseases.

Clinical characteristics of a case of developmental and epileptic encephalopathy caused by PPP3CA gene mutation and literature review / 中华神经科杂志

Objective:To improve clinicians′ understanding of developmental and epileptic encephalopathy (DEE) caused by PPP3CA gene mutation. Methods:Clinical data of a patient with DEE diagnosed in the First Department of Neurology, Hebei Children′s Hospital in September 2018 were collected. The whole-exome sequencing of the proband′s family was performed, and the characteristics of gene mutation were analyzed. Literature review was carried out based on the reported cases related to PPP3CA gene. Results:The proband, a 3 months and 20 days old girl, was admitted to the hospital with a history of paroxysmal confusion with extremities shaking for 2 days. The clinical manifestations included frequent epilepsy seizures and hypoevolutism. Brain magnetic resonance imaging showed that the bilateral frontotemporal extracerebral space was slightly wider. The video electroencephalography showed hyperarrhythmia and a cluster of spastic seizures. Whole exome sequencing of the family revealed that the proband had a heterozygous de novo frameshift truncating mutation in the PPP3CA gene: c.1255-1256delAG (p.Ser419Cysfs*31). From the establishment of the database to May 2022, 8 foreign literatures and 1 Chinese literature were retrieved, and a total of 21 children with PPP3CA gene mutation were reported, with clinical developmental delay, cognitive dysfunction and abnormal electroencephalography activity. Conclusions:The frameshift truncating mutation of the PPP3CA gene (c.1255-1256delAG) is the hereditary etiology of this patient. For cases of frequent seizures with poor efficacy of antiepileptic drugs, and developmental delay, genetic testing should be performed to confirm diagnosis and treatment.

Primary ciliary dyskinesia in children: a case report and literature review / 中国综合临床

Objective:To explore the clinical features and diagnostic methods of primary ciliary dyskinesia (PCD).Methods:A case of PCD diagnosed by Kunming Children's Hospital was analyzed retrospectively (including general information, clinical characteristics, auxiliary examination results), and the literature was reviewed.Results:The patient, an 8-year-old female, went to hospital for repeated cough and suffered from pneumonia and sinusitis repeatedly in the past. The electron microscope of cilia biopsy showed that the number of cilia was reduced. The mutation of c.7615T>C (p.W2539R) in DNA H5 gene located in chr5-13,809,290 was detected by gene test, so the patient was diagnosed as PCD.The mutation site was a new mutation site.Conclusion:PCD is a rare disease in children. Electron microscopy and genetic examination are helpful to the diagnosis of PCD. Children with recurrent respiratory tract infection and wet cough should be alert to the possibility of PCD.

Symptom scores of patients with chronic obstructive pulmonary disease and their response to different inhalation drug treatments / 中国医师杂志

Objective:To analyze the response of patients with chronic obstructive pulmonary disease (COPD) with multiple and few symptoms to different inhalation drugs, including acute exacerbation and symptom changes.Methods:This study was a multi center, retrospective Cohort study. The subjects of this study were patients with chronic obstructive pulmonary disease in stable stage in 12 hospitals in Hunan and Guangxi from December 2016 to February 2022. Demographics data, lung function, Chronic Obstructive Pulmonary Disease Assessment test questionnaire (CAT) score, modified British Medical Research Council dyspnea questionnaire (mMRC) score and inhalation drug scheme of patients were collected. According to the CAT and mMRC scores, patients were divided into a multi symptom group (CAT≥10 points or mMRC≥2 points) or a few symptom group (CAT<10 points and mMRC<1 point); Subsequently, they were divided into four subgroups based on the inhalation drug regimen: long-acting anticholinergic drugs (LAMA) group, long-acting β2-receptor agonists (LABA)+ inhaled corticosteroids (ICS) group, LABA+ LAMA group, and LABA+ LAMA+ ICS group. All patients were followed up for 1 year, with minimum clinical improvement (MCID) defined as a decrease of ≥2 points in the patient′s CAT score at 6 months, and clinical symptom deterioration (CSD) defined as an increase of ≥2 points in the patient′s CAT score at 6 months.Results:A total of 929 patients with chronic obstructive pulmonary disease were included, including 719(77.4%) with multiple symptoms and 210(22.6%) with few symptoms. There was no statistically significant difference in MCID, CSD, acute exacerbation, hospitalization frequency, and mortality rate among subgroups of asymptomatic COPD patients treated with different inhalation drug regimens (all P>0.05). Among patients with multiple symptoms of chronic obstructive pulmonary disease, compared to those who use LAMA or LABA+ ICS, those who used LABA+ LAMA or LABA+ LAMA+ ICS were more likely to obtain MCID and had a more significant improvement in CAT scores, and the risk of acute exacerbation is lower (all P<0.05). Conclusions:Lesser symptomatic COPD patients should receive single drug LAMA as the initial inhalation treatment drug, while multi symptomatic COPD patients should receive LABA+ LAMA as the initial inhalation treatment drug.