Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

Objective To investigate the effect of cysteine-rich acidic secretory protein-like protein 1(SPARCL1)on atherosclerosis(AS)plaque formation.Methods A case-control study design was used,394 patients with con-firmed AS were selected as the case group,and 394 healthy medical examiners matched for age and gender were se-lected as the control group.The expression level of serum SPARCL1 was determined by enzyme-linked immunosor-bent assay;immunohistochemistry was used to assess the expression level and localization of SPARCL1 protein in the AS plaque region,and the expression of SPARCL1 protein was also detected in the neutrophils and monocytes of peripheral blood of AS patients and normal controls;SPARCL1 overexpressing and the recombinant adenoviral vec-tors were constructed to inhibit SPARCL1 overexpression and expression,and the effects of SPARCL1 on cell mi-gration were observed in the cell scratch assay using mouse macrophage cells(J774A.1)as target cells.Results Serum SPARCL1 levels in the AS patient group were lower than those in the healthy group(P<0.05);high SPARCL1 expression was detected in AS plaques and was mainly expressed in the cytoplasm of foamy cells;SPARCL1 expression levels in peripheral blood neutrophils and monocytes were lower than those in normal controls in AS patients(P<0.05);recombinant SPARCL1 overexpression and inhibition of expression of adenovirus was successfully constructed;the cell migration rate was decreased in J774A.1 cells that inhibited SPARCL1 expression and increased in J774A.1 cells that overexpressed SPARCL1(P<0.05).Conclusion SPARCL1 is highly ex-pressed in foam cells at the site of AS lesions,which may result from compensatory recruitment of peripheral blood monocytes and neutrophils,and SPARCL1 may be involved as a protective factors for blood vessels in inhibiting the development of AS plaques.

Background Lung cancer is a malignancy of high incidence rate and mortality in China.The fear of relapse can affect the patient's treatment compliance and reduce their quality of life.There have been previous studies on the relationship between fear of lung cancer relapse and disease perception,as well as disease perception and psychological flexibility.However,current research on the status quo of fear of lung cancer relapse and its correlation with illness perception and psychological flexibility is limited.Objective To explore the fear of cancer relapse and its relations with illness perception and psychological flexibility in patients with lung cancer,and to provide references for subsequent related clinical interventions.Methods A total of 96 patients were selected as the research subjects,who were pathologically diagnosed with lung cancer and admitted to Fuyang People's Hospital from January 2021 to July 2022.Fear of Progression Questionnaire-Short Form(FoP-Q-SF),Brief Illness Perception Questionnaire(BIPQ)and Acceptance and Action Questionnaire-Ⅱ(AAQ-Ⅱ)were used for evaluation.Pearson correlation analysis was used to examine the correlation between scores of various scales,and multiple linear regression analysis was used to explore the influencing factors of relapse fear in lung cancer patients.Results The total FoP-Q-SF score of lung cancer patients was(35.35±7.66)and a total of 65 cases(67.71%)had a FoP-Q-SF score&ge;34.As relevant analyses showed,the BIPQ total score of lung cancer patients was positively correlated with the total score,social family dimension score and physiological health dimension score of Fop-Q-SF(r=0.586,0.445,0.475,P<0.05),the AAQ-Ⅱ score was positively correlated with the total score,social family dimension score and physiological health dimension score of FoP-Q-SF(r=0.485,0.652,0.513,P<0.05).According to the results of single factor analysis and multiple linear regression analysis,age(β=-0.142,P<0.01),education level(β=-0.254,P<0.01),monthly household income(β=-0.527,P<0.01),illness perception(β=0.847,P<0.01)and psychological flexibility(β=0.781,P<0.01)are all factors influencing the fear of relapse in lung cancer patients.Conclusion Most lung cancer patients have a fear of recurrence.It is not only related to illness perception and psychological flexibility,but also influenced by factors including age,education level and monthly family income.

Objective To study the expression and clinical significance of neural Wiskott-Alrdich syndrome protein(N-WASP)in pla-centas with preeclampsia.Methods This study included a total of 65 pregnant women:15 in the early-onset preeclampsia group,15 in the early-onset control group,15 in the late-onset preeclampsia group,and 20 in the late-onset control group.Real-time fluorescence quan-titative PCR(RT-qPCR)was used to detect the relative expression of N-WASP mRNA in placental tissues.Western blotting and immu-nohistochemistry were used to detect the expression and position of N-WASP protein in placental tissues from each group.Results RT-qPCR revealed significantly lower N-WASP mRNA expression levels in the placental tissue of the early-onset preeclampsia group compared to those in the early-onset control group(0.50±0.19 vs.0.93±0.73,P＜0.05).The N-WASP mRNA expression levels in late-onset preeclampsia placenta were significantly lower than those in the late-onset control group(0.83±0.34 vs.1.15±0.34,P＜0.05).Western blotting revealed significantly lower N-WASP protein expression in the placental tissue of early-onset preeclampsia compared to that in the early-onset control group(0.35±0.17 vs.0.72±0.21,P＜0.05).The N-WASP protein expression in late-onset preeclampsia placenta was significantly lower than that in the late-onset control group(0.39±0.16 vs.0.76±0.20,P＜0.05).The N-WASP mRNA expression in the placenta negatively correlated with the occurrence of early-onset(r =-0.37,P = 0.042)and late-onset preeclampsia(r =-0.39,P = 0.019).Immunohistochemistry revealed that N-WASP protein was localized in the cytoplasm of syncytiotrophoblasts,cytotrophoblasts,villous stromal cells,and vascular endothelial cells.Conclusion The low expression of N-WASP may be closely associated with preeclampsia.

  Objective   To systematically assess the applicability of the clinical practice guidelines (CPGs) integrating Chinese and western medicine, thereby providing reference for enhancing their future usability.   Methods   PubMed, Web of Science, Embase, SinoMed, WanFang Data, and CNKI databases were searched for guidelines for the integration of Chinese and western medicine. Supplementary searches of Chinese Medical Association, Chinese Medicine Administration, MedSci websites, Website of China Association of Chinese Medicine, Medlive, Website of Dangdang, Chinese Association of Integrative Medicine and World Federation of Traditional Chinese Medicine Societies were conducted. The search time frame was from inception of the databases to December 31, 2022. Four reviewers independently evaluated the implementability of clinical practice guidelines by using "Clinical Practice Guideline (CPG) implementation evaluation tool".   Results   A total of 61 integrative Chinese and western medicine guidelines were included. Of the guidelines assessed, 9 guidelines(14.75%) exhibited strong implementability, 40(65.57%) demonstrated average implementability, and 12 (19.67%) demonstrated poor implementability. Among the 5 domains, the dimensions of "accessibility" and "implementability" were found to be of high quality, while those of "communication", "ease of identification" and "applicability" were relatively poor. Notably, compared to guidelines published between 2006—2016, those published between 2017—2022 showed improvements in the areas of "identification" and "application".   Conclusions   The implementabilityof the existing clinical practice guidelines of the integrative Chinese and western medicine is average and needs to be improved. In the future, emphasis should be placed on the integration of medical education and research, publicity of the guidelines, continuous medical education and training, a more concise form of recommendations, application of the guidelines by clinicians, and the implementability of the integrative Chinese and western medicine guideline.

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) titration based on open-lung strategy on the intraoperative thoracic fluid content (TFC) in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy (TULIP).Methods:Eighty-six American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, patients, aged 65-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective TULIP, were divided into 2 groups ( n=43 each) by the random number table method: fixed PEEP group (group C) and individualized PEEP titration group (group P). PEEP was set at 4 cmH 2O after routine mechanical ventilation in group C. Patients underwent pulmonary recruitment maneuvers combined with individualized PEEP titration during surgery in group P. TFC was measured using a non-invasive cardiac output monitor at 5 min after tracheal intubation (T 0), 30 min after PEEP titration and ventilation (T 1), 5 min before surgery (T 2), and 5 min before leaving the recovery room (T 3). Cardiac output, oxygenation index and stroke volume index were recorded from T 0-T 2, arterial blood gas analysis was simultaneously performed to record peak airway pressure and dynamic lung compliance, and oxygenation index was calculated. The duration of postanesthesia care unit stay, pulmonary complications within 7 days after surgery, and length of hospital stay were also recorded. Results:Eighty-three patients were finally included, with 42 in group C and 41 in group P. Compared with group C, TFC was significantly decreased at T 1-T 3, cardiac index, cardiac output and stroke volume index were decreased at T 1, dynamic lung compliance, PaO 2 and oxygenation index were increased at T 1 and T 2, PaCO 2 was decreased, the incidence of postoperative pulmonary complications was reduced, and the duration of postanesthesia care unit stay and postoperative length of hospital stay were shortened in group P ( P<0.05). Conclusions:Individualized PEEP titration based on open-lung strategy can effectively decrease TFC and improve intraoperative oxygenation and prognosis in elderly patients undergoing TULIP.

Objective:To evaluate the feasibility of utilizing artificial intelligence (AI) to assist junior anesthesia residents in making the preoperative anesthesia plans.Methods:Forty anesthesia residents in their third year of training, who had obtained their practicing physician qualifications in the Yangzhou area, were assigned into 4 groups ( n=10 each) using a random number table method: Chat-GPT combined with Bing chat group (C-G-B group), Chat-GPT group (C-G group), Bing chat group (B group), and control group (C group). Fifty patients undergoing elective non-cardiac surgery were selected from the anesthesia clinic as teaching cases. C-G-B, C-G and B groups utilized different AI tools to assist trainees in designing anesthesia plans, producing standardized textual outputs. Each trainee underwent a baseline knowledge test through a professional theory examination prior to enrollment. The completeness and accuracy of the preoperative anesthesia plans were evaluated and scored by 3 chief anesthesiologists. The total time spent on plan formulation and satisfaction scores regarding AI tool feedback were recorded. An analysis was conducted based on the American Society of Anesthesiologists (ASA) Physical Status classification of teaching cases. Results:In ASA Physical Status classification Ⅰ and Ⅱ teaching cases, there was no statistically significant difference in completeness and accuracy scores among the four groups ( P>0.05). In ASA Physical Status classification Ⅲ teaching cases, compared to C group, the completeness and accuracy scores were significantly increased in C-G-B, C-G and B groups, with the highest scores observed in C-G-B group ( P<0.05). Among all teaching cases (ASA Physical Status classification Ⅰ-Ⅲ), the total time spent was significantly shortened in C-G and B groups as compared to C and C-G-B groups ( P<0.05). There was no statistically significant difference in the total time spent between C-G group and C-G-B group ( P>0.05). Compared to C-G and B groups, the satisfaction score was significantly decreased in C-G-B group ( P<0.05). Conclusions:For ASA Physical Status classification Ⅲ patients, using AI to assist junior anesthesia residents in making preoperative anesthesia plans may offer advantages. Although combining the use of Chat-GPT and Bing chat can further improve the completeness and accuracy of anesthesia plan development, it may require more time.

Objective:To evaluate the effect of controlled low central venous pressure (CLCVP) induced by milrinone on intraoperative cerebral blood flow in the patients undergoing laparoscopic hepatectomy.Methods:Eighty American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, regardless of gender, scheduled for elective laparoscopic hepatectomy, with body mass index of 18-30 kg/m 2, aged 18-64 yr, were divided into 2 groups ( n=40 each) by a random number table method: nitroglycerin group (X group) and milrinone group (M group). After the start of surgery, milrinone 0.5 μg·kg -1·min -1 was continuously infused in group M and nitroglycerin 0.5-1.5 μg·kg -1·min -1 was continuously infused in group X to maintain central venous pressure (CVP)<5 cmH 2O. Norepinephrine 0.01-0.10 μg·kg -1·min -1 was intravenously injected during operation to maintain mean arterial pressure at 60-90 mmHg. Norepinephrine 8-16 μg was intravenously injected when necessary. At 10 min after tracheal intubation (T 1), after establishment of pneumoperitoneum (T 2), at 5 and 30 min after CVP reached the target value (T 3, T 4), at 5 min after CVP returned to normal value (T 5) and at the end of surgery (T 6), the internal carotid artery mean blood flow velocity, internal carotid artery blood flow, cardiac output, and cardiac index were recorded. The surgical field score, consumption of intraoperative norepinephrine, fluid input and output, and occurrence of adverse reactions at 7 days after operation were recorded. Results:Compared with group X, the cardiac output, cardiac index, internal carotid artery mean blood flow velocity and internal carotid artery blood flow were significantly increased, the consumption of intraoperative norepinephrine was decreased, and the surgical field score was increased at T 3-5 in group M ( P<0.05). There was no significant difference in the intraoperative fluid intake and output and incidence of postoperative adverse reactions at each time point between the 2 groups ( P>0.05). Conclusions:Compared with nitroglycerin-induced CLCVP, milrinone-induced CLCVP can improve the reduction in intraoperative cerebral blood flow in the patients undergoing laparoscopic hepatectomy to some extent.