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 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 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 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.

  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 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 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 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 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.