Bronchial asthma （BA） is a common chronic inflammatory airway disease characterized by airway hyperresponsiveness and reversible airflow limitation. Lung macrophages （LMs）， as important effector cells of the innate immune system， play an important role in recognizing and engulfing pathogens， clearing harmful particles， and regulating immune responses. LMs can be polarized to M1 （pro-inflammatory） or M2 （anti-inflammatory） in different immune environments and participate in promoting or inhibiting inflammatory response， as well as lung parenchyma injury and repair （airway remodeling）， playing a key role in the BA occurrence and development. Regulating the polarization balance of macrophages can not only inhibit the inflammatory response in the airway and reduce airway hyperresponsiveness， but also improve airway remodeling and immune regulation， reduce airway mucus secretion， and alleviate the clinical BA symptoms. Traditional Chinese medicine and its active ingredients， especially polysaccharides and saponins， can regulate the polarization balance of M1/M2 macrophages. Traditional Chinese medicine compounds can balance the secretion of anti-inflammatory and pro-inflammatory factors by staging treatment and targeting the polarization state of M1/M2 macrophages， inhibit inflammatory response in the airway， reduce airway remodeling， and improve the BA symptoms. This paper summarized the research progress on the regulation of M1/M2 macrophage polarization by traditional Chinese medicine and its active ingredients， aiming to provide scientific evidence for the precise targeted therapy of BA.

Bronchial asthma （BA） is a common chronic inflammatory airway disease characterized by airway hyperresponsiveness and reversible airflow limitation. Lung macrophages （LMs）， as important effector cells of the innate immune system， play an important role in recognizing and engulfing pathogens， clearing harmful particles， and regulating immune responses. LMs can be polarized to M1 （pro-inflammatory） or M2 （anti-inflammatory） in different immune environments and participate in promoting or inhibiting inflammatory response， as well as lung parenchyma injury and repair （airway remodeling）， playing a key role in the BA occurrence and development. Regulating the polarization balance of macrophages can not only inhibit the inflammatory response in the airway and reduce airway hyperresponsiveness， but also improve airway remodeling and immune regulation， reduce airway mucus secretion， and alleviate the clinical BA symptoms. Traditional Chinese medicine and its active ingredients， especially polysaccharides and saponins， can regulate the polarization balance of M1/M2 macrophages. Traditional Chinese medicine compounds can balance the secretion of anti-inflammatory and pro-inflammatory factors by staging treatment and targeting the polarization state of M1/M2 macrophages， inhibit inflammatory response in the airway， reduce airway remodeling， and improve the BA symptoms. This paper summarized the research progress on the regulation of M1/M2 macrophage polarization by traditional Chinese medicine and its active ingredients， aiming to provide scientific evidence for the precise targeted therapy of BA.

Objective In response to the practical issues of pilot ground simulation ejection training relying on subjective evaluation,which requires high professionalism and lacks objectivity and systematicity,an objective evaluation system and method for ejection training based on pressure detection has been designed.Methods According to the rules of ejection training about posture,maneuver and time,and utilizing technologies such as pressure detection,infrared detection,and time-triggered detection,this paper designed separate modules for ejection posture detection,ejection timing detection,and comprehensive analysis and evaluation.These modules are closely integrated with the ejection training process,achieving objective evaluation of the ejection training.Results This system and method can provide a scientific and real-time objective evaluation of the posture,movements,and time in ejection training without affecting the normal organization and process.Conclusion The objective evaluation system can provide a new approach that is highly objective and easy to operate for comprehensively evaluating and enhancing the effectiveness of ejection training,as well as for scientifically conducting ejection training and assessment.

Objective:To evaluate the efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy.Methods:In this multicenter, non-inferiority, randomized controlled trial, 300 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-60 yr, with body mass index of 18-28 kg/m 2, who underwent daytime laparoscopic cholecystectomy under general anesthesia with tracheal intubation at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou First People′s Hospital Affiliated to Westlake University School of Medicine, Ningbo No. 2 Hospital, and the Second Affiliated Hospital of Nanchang University from August 2021 to August 2023, were selected and divided into 2 groups ( n=150 each) using a random number table method: remimazolam group (R group) and propofol group (P group). Anesthesia was induced as follows: Sufentanil was intravenously injected at a rate of 0.5 μg/kg, remimazolam was intravenously injected at a rate of 0.3 mg/kg in group R, propofol was intravenously injected at a rate of 2.0-2.5 mg/kg in group P, and cisatracurium besilate was intravenously injected at a rate of 0.2 mg/kg after loss of consciousness in two groups. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained as follows: Remimazolam was intravenously injected at a rate of 0.5-1.0 mg·kg -1·h -1 in group R, propofol was intravenously injected at a rate of 4-10 mg·kg -1·h -1 in group P, and remifentanil was intravenously infused at a rate of 0.25-2.00 μg·kg -1·min -1, maintaining intraoperative bispectral index value of 40-60. The success rate of sedation was recorded, and non-inferiority tests were conducted. The time to loss of consciousness, emergence time, extubation time, recovery time of orientation, time of stay in post-anesthesia care unit and occurrence of delayed emergence were recorded. Liver function and renal function were measured before operation and within 24 h after operation. The occurrence of abnormal alanine transaminase, abnormal aspartate transaminase, abnormal creatinine and abnormal urea was recorded. The occurrence of adverse reactions during and after operation was recorded. Results:The success rates of sedation were 98.6% and 99.3% in group R and group P, respectively, there was no statistically significant difference in the success rate of sedation between the two groups ( P>0.05), and the difference in the success rates of sedation between the two groups was -0.007 (95% confidence interval-0.0301-0.0161), which met the pre-set non-inferiority criteria(95% confidence interval >-0.055). Compared with group P, the time to loss of consciousness and recovery time of orientation were significantly prolonged, and the incidence of delayed emergence was increased ( P<0.05), and no statistically significant changes were found in the emergence time, extubation time, time of stay in post-anesthesia care unit and severity of postoperative nausea and vomiting in group R ( P>0.05). There was no statistically significant difference in the abnormal rates of alanine transaminase, aspartate transaminase, creatinine and urea before and after operation between the two groups ( P>0.05). Conclusions:The efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy is not inferior to that of propofol-based anesthesia.

Objective:To evaluate the efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy.Methods:In this multicenter, non-inferiority, randomized controlled trial, 300 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-60 yr, with body mass index of 18-28 kg/m 2, who underwent daytime laparoscopic cholecystectomy under general anesthesia with tracheal intubation at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou First People′s Hospital Affiliated to Westlake University School of Medicine, Ningbo No. 2 Hospital, and the Second Affiliated Hospital of Nanchang University from August 2021 to August 2023, were selected and divided into 2 groups ( n=150 each) using a random number table method: remimazolam group (R group) and propofol group (P group). Anesthesia was induced as follows: Sufentanil was intravenously injected at a rate of 0.5 μg/kg, remimazolam was intravenously injected at a rate of 0.3 mg/kg in group R, propofol was intravenously injected at a rate of 2.0-2.5 mg/kg in group P, and cisatracurium besilate was intravenously injected at a rate of 0.2 mg/kg after loss of consciousness in two groups. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained as follows: Remimazolam was intravenously injected at a rate of 0.5-1.0 mg·kg -1·h -1 in group R, propofol was intravenously injected at a rate of 4-10 mg·kg -1·h -1 in group P, and remifentanil was intravenously infused at a rate of 0.25-2.00 μg·kg -1·min -1, maintaining intraoperative bispectral index value of 40-60. The success rate of sedation was recorded, and non-inferiority tests were conducted. The time to loss of consciousness, emergence time, extubation time, recovery time of orientation, time of stay in post-anesthesia care unit and occurrence of delayed emergence were recorded. Liver function and renal function were measured before operation and within 24 h after operation. The occurrence of abnormal alanine transaminase, abnormal aspartate transaminase, abnormal creatinine and abnormal urea was recorded. The occurrence of adverse reactions during and after operation was recorded. Results:The success rates of sedation were 98.6% and 99.3% in group R and group P, respectively, there was no statistically significant difference in the success rate of sedation between the two groups ( P>0.05), and the difference in the success rates of sedation between the two groups was -0.007 (95% confidence interval-0.0301-0.0161), which met the pre-set non-inferiority criteria(95% confidence interval >-0.055). Compared with group P, the time to loss of consciousness and recovery time of orientation were significantly prolonged, and the incidence of delayed emergence was increased ( P<0.05), and no statistically significant changes were found in the emergence time, extubation time, time of stay in post-anesthesia care unit and severity of postoperative nausea and vomiting in group R ( P>0.05). There was no statistically significant difference in the abnormal rates of alanine transaminase, aspartate transaminase, creatinine and urea before and after operation between the two groups ( P>0.05). Conclusions:The efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy is not inferior to that of propofol-based anesthesia.

Objective To investigate whether embolization surgery can improve mid-to-long-term outcomes related to quality of life,anxiety and depression in patients with unruptured intracranial aneurysms(UIA).Methods This prospective study included patients diagnosed with UIA within 30 days.Patients were divided into two groups based on treatment:the embolization group and the conservative group.The assessments of quality of life,depression,and anxiety were conducted using the medical outcome study short form-36(SF-36),self-rating depression scale(SDS),and self-rating anxiety scale(SAS)at baseline,3 months,and 5 years after treatment.In the embolization group,psychological trauma was assessed using the impact of event scale-revised(IES-R)at 3 months and 5 years post-surgery.Results A total of 113 patients were involved in the analysis including 76 in the embolization group and 37 in the conservative group.Compared to the conservative group,SF-36 data showed that the embolization group had a lower physical function(80.3±16.4 vs.86.1±12.8,P=0.046)and role-physical(47.37±43.32 vs.67.57±34.29,P=0.015)scores at 3 months,but a higher mental health score(68.16±18.80 vs.61.62±14.62,P=0.048).At 5 years,all dimensions of SF-36 improved significantly compared to baseline(all P<0.05).The SDS and SAS scores in the embolization group were significantly lower at both 3 months and 5 years compared to baseline(both P<0.05).The decrease in SDS(-2.8±10.6 vs.0.5±6.5)and SAS(-2.7±11.8 vs.1.2±5.4)scores in the embolization group at 3 months was greater than in the conservative group(both P<0.05).Subgroup analysis showed that patients with depression or anxiety at baseline in the embolization group experienced a significant decrease in SDS and SAS scores at 3 months and 5 years compared to baseline(both P<0.05).Additionally,in the embolization group,the IES-R score at 3 months was 37.5±13.8,which was significantly higher than the critical threshold(P=0.005),but decreased to 33.8±13.3 at 5 years post-surgery.Conclusions Patients with unruptured intracranial aneurysms experienced long-term improvements in quality of life after embolization surgery.Embolization surgery also helped alleviate depression and anxiety.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective:To investigate the role of miR-144-3p in cisplatin resistance of bladder cancer.Methods:Bladder cancer T24 cells were cultured in vitro and divided into blank group (untreated), mimetic control group, miR-144-3p mimetic transfection group, inhibitor control group, and miR-144-3p inhibitor transfection group. Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to verify the transfection effect, methyl thiazolyl tetrazolium (MTT) method was used to detect the survival rate of cells treated with cisplatin in each group, and Western blot was used to detect the expression of the target protein. The targeting relationship between miR-144-3p and nuclear factor E2 related factor 2 (Nrf2) was validated using dual fluorescence reporter gene experiments. Furthermore, Nrf2 was knocked out in each group of cells, and the mRNA and protein expression levels of HO-1, Bcl-2, and Caspase-3 were detected by qRT-PCR and Western blot in each group of cells.Results:Compared with the control group, bladder cancer cells in the miR-144-3p mimetic transfection group were more sensitive to cisplatin, while the miR-144-3p inhibitor transfection group had the opposite effect; The miR-144-3p simulant transfection group can effectively inhibit the mRNA and protein expression level of Nrf2 in bladder cancer cells (all P<0.05), while the miR-144-3p inhibitor transfection group can up regulate the mRNA and protein level of Nrf2 (all P<0.05). The miR-144-3p mimetic transfection group showed significant downregulation of mRNA and protein expression of HO-1 and Bcl-2, while the expression of Caspase-3 was upregulated (all P<0.05), while the miR-144-3p inhibitor transfection group showed the opposite results. The luciferase results confirmed that miR 144 3p can directly bind to the 3′- UTR region of Nrf2, reducing the mRNA level of Nrf2. When Nrf2 was knocked out, whether miR-144-3p mimetic transfection group or miR-144-3p inhibitor transfection group, the mRNA and protein expression levels of HO-1, Bcl-2 and Caspase-3 did not change significantly, and miR-144-3p lost the ability to regulate the cisplatin sensitivity of bladder cancer cells. Conclusions:miR-144-3p targets to regulate the sensitivity of Nrf2 to cisplatin in bladder cancer, and miR-144-3p is expected to become a new target for the treatment of cisplatin resistant or refractory bladder cancer.

Objective    To explore the risk factors and predictive value of acute kidney injury (AKI) after total aortic arch replacement. Methods    The clinical data of patients undergoing total aortic arch replacement in our hospital from January 2018 to June 2019 were retrospectively analyzed, and patients receiving preoperative renal replacement therapy and missing creatinine values were excluded. According to whether postoperative AKI occurred, patients were divided into an AKI group and a control group. The univariate and multivariate analyses (logistic regression) were used to explore the independent risk factors of AKI. The receiver operating characteristic curve was used to analyze the significant factors in predicting the occurrence of AKI after total aortic arch replacement. Results    A total of 162 patients were included in the study, including 135 (83.3%) males and 27 (16.7%) females, with an average age of 52.61±9.90 years (range: 22 to 73 years). The incidence of AKI was 68.5% (n=111). The results of univariate and multivariate analyses showed that the postoperative serum cystatin C level (OR=76.145, 95%CI 15.575-372.260, P<0.01) was an independent risk factor for AKI after total aortic arch replacement. When its cut-off value was above 1.08 mg/L, the specificity for predicting postoperative AKI was 70.59%, and the sensitivity was 85.59%. Conclusion    The postoperative cystatin C level is an independent risk factor for AKI after total aortic arch replacement and has predictive value.