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

Objective:To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A.Methods:It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed.Results:The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband′s father had knee joint pain. The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions:High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

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 This study aims to assess the hazard vulnerability risks in emergency wards to enhance their flexibility and resilience in response to unexpected events.Methods A cross-sectional survey of 73 emergency specialist nurses from 39 hospitals in Zhejiang province was conducted to identify potential threats,assess their probability,and estimate their impact on specific organizations or regions using hazard vulnerability analysis(HVA)based on Kaiser model.The risk values associated with such events were calculated.Results Among the four categories of risk indicators,the highest risk value was attributed to the"system"(37.68％),followed by"staff'(36.53％),"stuff'(29.45％),and"space"(29.25％).The top 10 ranked risk events included exceeding emergency room capacity with patient numbers(52.03％),insufficient staff(47.23％),workplace violence(46.86％),medical litigation(43.64％),accidental removal of high-risk tubes(41.63％),lack of rescue experience or skills(41.51％),specimen errors(40.72％),inadequate experience in observing and handling circulatory support abnormalities(39.22％),information system failures(38.95％),and patient elopement(38.28％).Conclusion Improvements should be made in areas such as leadership planning,system enhancement,communication and collaboration,and adaptability.Emergency ward preparedness and service quality can be further enhanced through measures such as strengthening nurse training and staffing,continuously monitoring item and space-related risks,and implementing bed management and new nurse training programs.

  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 investigate the protective effect and mechanism of ginsenoside Rg1(G-Rg1)on interleukin-6(IL-6)-induced neuronal injury in rats by regulating Janus activated kinase(JAK)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods After culture,rat hippocampal neurons were divided into the control group(normal culture),the IL-6 model group(50 μg/L IL-6 was used to treat rat hippocampal neurons for 18 h to simulate the inflammatory environment in brain),the G-Rg1 low dose(10 μmol/L)group and the G-Rg1 high dose(40 μmol/L)group.After 48 h of normal culture,the survival rate of hippocampal neurons was determined by MTT method.The total iron load of neurons was detected by spectrophotometry,and levels of ferroptosis markers glutathione(GSH)and glutathione peroxidase 4(GPX4)were detected.The mRNA expression level of ferroportin 1(FPN1)in hippocampal neurons was detected by qRT-PCR.The expression of proteins related to the neuronal JAK/STAT3 signaling pathway was detected by Western blot assay.Results Compared with the CON group,the neuronal survival rate,GSH content,GPX4 content and FPN1 mRNA expression level were decreased in the IL-6 model group,and the total iron load,p-JAK and p-STAT3 protein expression levels were increased(P＜0.05).Compared with the IL-6 model group,the neuronal survival rate,GSH content,GPX4 content and FPN1 mRNA expression level were increased in the low-dose and high-dose G-Rg1 groups,and the total iron load,p-JAK and p-STAT3 protein expression levels were decreased(P＜0.05).Changes of the above indicators were more significant in the high-dose G-Rg1 group than those in the low-dose G-Rg1 group(P＜0.05).Conclusion The mechanism of G-Rg1 alleviating ferroptosis of hippocampal neurons in rats may be related to the inhibition of IL-6/JAK/STAT3 signaling pathway,up-regulation of FPN1 expression,and prevention of iron overload.

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 evaluated the safety and feasibility of dissection of lymph nodes posterior to right recurrent laryngeal nerve (ⅥB compartment) in endoscopic thyroidectomy through gasless axillary posterior approach.Methods:A total of 350 cases with right lobe papillary thyroid carcinoma (PTC) who underwent endoscopic lobectomy, isthmusectomy and central compartment neck dissection via gasless axillary posterior approach based at the Department of General Surgery, Nanfang Hospital, Southern Medical University from June 2020 to December 2022 were retrospectively analyzed. Summarize the clinical, pathological characteristics, and postoperative complications of the patients. SPSS 25.0 was used for statistical analysis of the data.Results:All 350 patients underwent endoscopic surgery successfully, with no conversion to open surgery. There were 303 females and 47 males, with an average age of (36.3±9.2) years. Of those, 287 patients were in pT1a stage, 62 in pT1b stage, and one patient in pT2 stage. There was no T3 or T4 stage patient. The mean numbers of yielded lymph nodes in right central compartment and ⅥB compartment were 8.11±4.65 (range, 1-31) and 2.62±1.86 (range, 1-12), respectively. ⅥB compartment metastasis was detected in 52 (14.86%) of 350 patients. The incidence of transient recurrent laryngeal nerve injury was 0.86%(3/350). Postoperative hematoma occurred in three patients (0.86%).Conclusion:The dissection of ⅥB compartment in endoscopic thyroidectomy through gasless axillary posterior approach is safe and feasible in selected PTC patients

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.