Objective To observe the effects of amyloid-β(Aβ)receptor PirB on mouse astrocyte proliferation and reactive astrogliosis in vitro.Methods Mouse primary astrocytes were cultured,and divided into control group,Aβ group,Aβ+0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group,Aβ+Fluspirilene group,Aβ+GFP-LV group,and Aβ+mPirB-LV group.The mouse astrocytes were treated with soluble PirB extracellular peptide PEP or PirB inhibitor Fluspirilene,respectively,to inhibit endogenous PirB receptor,or overexpressed PirB gene via lentivirus transfection and then treated with Aβ1-42 oligomers.The proliferation of astrocytes was observed by RTCA and EdU methods,and the mRNA expression levels of S-100 calcium-binding protein B(S-100β),Vimentin,Nestin and amyloid precursor protein(APP)associated with reactive astrogliosis of astrocytes were observed by real-time PCR,and the expression level of glial fibrillary acid protein(GFAP)was detected by Western-blotting.Results The results of RTCA monitoring showed that normalized cell index(NCI)values of each group decreased sharply after treatment,and then increased gradually and tended to be stable.The results of EdU staining showed that the proliferative activity of astrocytes was significantly enhanced in the Aβ group(P<0.05)compared with control group;Compared with Aβ group,cell proliferation activity in Aβ + 0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group and Aβ+Fluspirilene group were significantly decreased(P<0.01 or P<0.001).The results of real-time PCR showed that compared with control group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ group were significantly increased(P<0.05);Compared with Aβ group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ+0.4 μmol/L PEP group were significantly decreased(P<0.01);Compared with Aβ+GFP-LV group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ +mPirB-LV group were significantly increased(P<0.05).The results of Western blotting showed that compared with control group,the expression of GFAP in Aβ group was significantly increased(P<0.05);Compared with Aβ group,the expression of GFAP in Aβ+0.4 μmol/L PEP group was significantly decreased(P<0.05).Conclusions PirB is an upstream molecule which could regulate astrocyte proliferation and reactive astrogliosis,and inhibiting PirB receptor in astrocytes may be a potential treatment for Alzheimer's disease.

Objective To observe the effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12α hydroxylase(CYP8B1)in spontaneously hypertensive rats(SHR).Methods Fifty SHR were randomly divided into model group,control group(1.0 mg·kg-1·d-1 benazepril by gavage)and experimental-L,-M,-H groups(8.63,17.25 and 34.50 g·kg-1·d-1 Zhengan Xifeng decoction by gavage),another 10 homologous male Wistar-Kyoto(WKY)rats were taken as the normal group.The model group and the normal group were given the same amount of distilled water.The rats in the 6 groups were administered once a day for 8 weeks.The animal non-invasive sphygmomanometer was used to measure the blood pressure of rats in each group by tail-cuff method;the bile acid spectrum of rats in each group was detected by UPLC-MS/MS;the expression of CYP8B1 mRNA in rat liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction.Results The systolic blood pressure at the 8th week of the experimental-M,-H groups,control group,model group,normal group were(169.63±12.10),(170.32±9.64),(175.95±15.47),(189.47±7.42)and(146.40±9.45)mmHg;the diastolic blood pressure at the 8th week were(135.10±11.99),(129.73±15.10),(135.18±17.62),(149.20±8.83)and(110.53±10.92)mmHg;the relative expression levels of CYP8B1 mRNA were 3.36±0.94,5.45±1.46,4.29±0.95,0.89±0.14 and 1.00±0.00,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(P＜0.01,P＜0.05).Compared with the model group,the bile acid spectrum of experimental-L,-M,-H groups bile changed significantly,and a total of 9 different bile acids were found,which were hyodeoxycholic acid,glycohyodeoxycholic acid,glycochenodeoxycholic acid,glycoursodeoxycholic acid,α-muricholic acid,ursodeoxycholic acid,cholic acid,β-muricholic acid and glycocholic acid.Conclusion Zhengan Xifeng decoction may correct bile acid spectrum disorder of bile and reduce blood pressure by up-regulating liver CYP8B1 expression.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

Objective:To investigate the association of R wave peak time(RWPT)with severity of coronary artery disease and short-term prognosis in patients with acute coronary syndrome(ACS).Methods:A total of 133 ACS patients who were treated in Shenzhen Longhua District Central Hospital between January 2019 and June 2022 and received coronary angiography were selected.According to number of diseased coronary arteries,they were divided into single-vessel coronary disease group(n=43),double-vessel coronary disease group(n=51)and multi-vessel coronary disease group(n=39);according to severity of coronary artery disease,they were divided into mild group(n=40),medium group(n=48)and severe group(n=45).ECG indexes were compared among groups with different number of diseased coronary arteries and severity of coronary artery disease.Pearson correlation analysis was used to analyze corre-lation between ECG indexes and Gensini score;patients were divided into major adverse cardiovascular events(MACE)group(n=46)and no MACE group(n=87)according to presence of MACE during hospitalization.Clinical data were compared between two groups,and multivariate Logistic regression was used to analyze risk factors of MACE during hospi-talization in ACS patients.Results:QRS duration and RWPT significantly increased according to the order of single-ves-sel,double-vessel and multi-vessel coronary disease group(P＜0.05 or＜0.01);QRS duration and RWPT significantly increased according to the order of mild,medium and severe group(P＜0.05 or＜0.01).Pearson correlation analysis indi-cated that QRS duration and RWPT were significant positively correlated with Gensini score in ACS patients(r=0.222,0.557,P=0.010,＜0.001).Multivariate Logistic regression analysis indicated that hypertension,diabetes,RWPT,Gensini score and multi-vessel disease were independent risk factors for MACE during hospitalization in ACS patients(OR=3.171～9.360,P＜0.05 or＜0.01).Conclusion:RWPT is closely related to the severity of coronary artery disease in ACS patients.RWPT detection helps to guide risk stratification and secondary prevention of ACS patients,therefore im-prove their short-term prognosis.

Shiwei-Ruxiang-capsule (SWRXC) is a classic formulation widely used in the treatment of rheumatoid arthritis (RA). The study used liquid chromatography-tandem mass spectrometry (LC-MS/MS) serum untargeted metabolomics and high-throughput 16S rRNA gene sequencing association analysis to elucidate the mechanism of action of SWRXC for the treatment of Freund's complete adjuvant-induced RA. The results showed that SWRXC significantly improved symptoms and reduced serum cytokine levels in RA rats. Based on LC-MS/MS technology, metabolomics identified tryptophan metabolism, nucleotide metabolism and purine metabolism as the most relevant pathways for treatment. In addition, 16S rRNA sequencing results showed that SWRXC could ameliorate RA-induced intestinal microbial oncogenesis in rats. In conclusion, SWRXC can improve the morphology and structure of RA joint tissues, reduce serum factor levels, and may play a role in improving RA by modulating related metabolic pathways such as tryptophan metabolism, nucleotide metabolism and purine metabolism, and altering the composition of intestinal flora. Animal protocols were approved by the Animal Ethics Committee of Qinghai Normal University (No. 2021041203).

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.
Humans ; Nonprescription Drugs ; Shock, Septic/drug therapy* ; Sepsis/drug therapy* ; Endotoxins ; Anticoagulants/therapeutic use*

Dynamic multi-leaf collimator, which has the function of radiation beam shaping, is a key executive component of tumor precise radiotherapy, and plays a core role in improving the accuracy, efficiency and quality of radiotherapy. A new type of collimator leaf end structure with circular arc and plane combination was studied, and collimator penumbra performance analysis model combining analytical expression and graphic analysis was developed. The influence of leaf end structure on penumbra was analyzed quantitatively, and a set of three-dimensional structure design of dynamic multi-leaf collimator was completed. The feasibility of the structural design and analysis model was verified through experimental measurements.
Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Particle Accelerators ; Neoplasms ; Radiotherapy Dosage

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.