Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

Objective To construct and validate a competency model for mental health professionals. Methods The literature analysis method, semi-structured expert interview method and Delphi method were used to construct the job competency model of mental health professionals. The hierarchical analysis method was used to construct the judgment matrix of each index and determine its weight coefficient. A total of 23 psychiatrists were selected as the validation subjects using the convenience sampling method to validate the model's effectiveness. Results The recovery rate of the valid correspondence questionnaire in this study was 100%, with an expert authority degree of 0.823, a coefficient of variation ranging from 0.070 to 0.101, and Kendall's W of 0.627-0.763 (all P<0.001). The constructed job competency model includes five primary indicators and 38 secondary indicators. The results of the consistency test (CR) showed that the CR value of the primary indicators was 0.028, and the CR values of the secondary indicators were 0.041, 0.034, 0.015, 0.020, and 0.032. The results of the hierarchical analysis showed that the weight ranking, in descending order, for primary indicators was knowledge, skills, ethical quality, intrinsic motivation, and personal traits. The top five secondary indicator combinations with the highest weights were basic clinical medicine knowledge, mental health professional knowledge, clinical diagnosis and treatment ability, medical ethics knowledge, and dedication to the job. The results of the validation analysis showed that the model scores for the 23 psychiatrists were consistent with their annual unit assessment results. Conclusion The constructed job competency model for mental health professionals can provide a reference for training and evaluation in mental health workforce development.

OBJECTIVE To explore the clinical efficacy of dapagliflozin for stable coronary heart disease combined with heart failure （HF）. METHODS A prospective study method was employed. A total of 158 patients with stable coronary heart disease and HF admitted to our hospital from January 1， 2023， to January 1， 2024， were enrolled. Using a random number table method， they were divided into dapagliflozin group （n＝76） and conventional treatment group （n＝82）. All patients received conventional treatment， including diuretic， aspirin， losartan， metoprolol and statins. Patients in the dapagliflozin group were additionally administered Dapagliflozin tablets at a dose of 10 mg once daily on top of the conventional treatment. The treatment duration was six months. The changes in left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， fasting blood glucose， N-terminal pro-brain natriuretic peptide （NT-proBNP）， the number of angina attacks， the duration of angina attacks， and lipoprotein-associated phospholipase A2 before and after treatment were compared between the two groups. The occurrence of adverse reactions such as renal dysfunction， liver dysfunction， urinary system infections， new-onset dialysis， hypotension and hypoglycemia was evaluated in the two groups during treatment. RESULTS During the study， 16 patients were lost to follow-up. Ultimately， 70 patients in the dapagliflozin group and 72 patients in the conventional treatment group completed the study. Before treatment， there were no statistically significant differences in the aforementioned indicators between the two groups （P＞0.05）. Compared with before treatment， after treatment， both groups showed significant shortening in LVESD and LVEDD， significant increases in LVEF， significant reductions in NT-proBNP and lipoprotein-associated phospholipase A2 levels， and significant reductions in the number of angina attacks and the duration of angina attacks （P＜0.05）； the improvements in the dapagliflozin group were more significant than those in the conventional treatment group （P＜0.05）. There was no statistically significant difference between the two groups in fasting blood glucose levels and the incidence of the aforementioned adverse reactions （P＞0.05）. CONCLUSIONS Adding dapagliflozin to conventional treatment can shorten LVESD and LVEDD， increase LVEF levels， reduce NT-proBNP and lipoprotein-associated phospholipase A2 levels， and decrease the number and duration of angina attacks in patients with stable coronary heart disease combined with HF， thereby improving their cardiac function， and demonstrates good safety.

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

BACKGROUND:Most scholars now believe that children with cerebral palsy who have severe spinal deformities in early childhood(<15 years of age)may have a higher risk of progression of spinal deformities,which may result from imbalances in movement due to pelvic tilt,pain,etc. OBJECTIVE:To investigate the relationship between lumbar spine development and hip joint development in children with spastic cerebral palsy. METHODS:A retrospective analysis was performed in 102 children with spastic cerebral palsy admitted at Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from January 2014 to December 2021.All admitted children had X-rays of the pelvic position and the lumbar lateral position.Anteroposterior X-ray of the pelvis was performed to measure femoral head migration percentage,central edge angle,neck-shaft angle,and acetabular index.The sagittal Cobb angle,sacral slope,arch-top distance,and lumbar lordosis index were measured by the lateral X-ray of the lumbar spine.Correlation of the two sets of indicators was further analyzed.All children were divided into normal group,risk group,hip subluxation group and total hip dislocation group according to their femoral head migration percentage,and the differences in lumbar spine indexes between groups were evaluated. RESULTS AND CONCLUSION:Pearson correlation analysis showed that the femoral head migration percentage was moderately positively correlated with sagittal Cobb angle and arch-top distance,and weakly positively correlated with lumbar lordosis index;the central edge angle was moderately negatively correlated with the arch-top distance and weakly negatively correlated with the sagittal Cobb angle;the neck-shaft angle was weakly positively correlated or not correlated with the sagittal Cobb angle and lumbar lordosis index;and the acetabular index was weakly positively correlated with the sagittal Cobb angle and arch-top distance.No statistically significant correlation was found between the remaining indicators.According to the femoral head migration percentage,the children were divided into four groups,including 25 cases in the normal group,41 cases in the risk group,27 cases in the hip subluxation group,and 9 cases in the total hip dislocation group.The sagittal Cobb angle was significantly increased in the risk group,the hip subluxation group and the total hip dislocation group compared with the normal group,showing an increasing trend group by group,and there were significant differences between groups(P<0.05).Compared with the normal group,the lumbar lordosis index in the risk group and the hip subluxation group increased significantly,and there were significant differences between groups(P<0.05).There was an increase trend in the lumbar lordosis index of the total hip dislocation group compared with the normal group.Compared with the normal group,the arch-top distance in the hip subluxation group and the total hip dislocation group increased significantly(P<0.05),and there was a stepwise increasing trend.There was no significant difference in sacral slope between groups.To conclude,the development of the lumbar spine in children with cerebral palsy is closely related to the development of the pelvic hip joint,and the most obvious relationship is between lumbar lordosis and hip dislocation.

The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.

Objective To analyze the causes of changes in the prevalence of respiratory diseases and the reason for changes in medical visit behavior of children in Zhejiang Province during the winter and spring seasons of 2019-2021, and to provide important reference for the allocation of hospital resources, implementation of hierarchical diagnosis and treatment, and epidemic prevention and control. Methods A retrospective study was conducted on 256 937 outpatient medical records from January 23rd to April 23rd of each year from 2019 to 2021 at the Children's Hospital Affiliated to Zhejiang University School of Medicine. Statistical methods were used for data analysis. Results A total of 256 937 cases were selected in the present study, including 157 000 cases in 2019, 22 192 cases in 2020, and 77 745 cases in 2021. The number of patients to the Children's Hospital of Zhejiang University School of Medicine from outside Hangzhou accounted for 41.74%, 14.36% , and 18.53% in 2019-2021, respectively. For 0~2 years old , 3~6 years old , and 7~14 years old groups , the percentages of patients with upper respiratory tract infections were 49.54%, 45.95%, and 46.74%, respectively ; with lower respiratory tract infections were 42.90% , 31.76% , and 22.95% ; with influenza were 2.23% , 3.15% and 4.09%; and with asthma were 1.37%, 5.08%, and 8.15%, respectively. Conclusion From 2019 to 2021, there have been significant changes in the total number of respiratory diseases in children, the proportion of disease types, and the proportion of children's geographical composition. It is necessary to continue to monitor children's respiratory diseases, grasp the dynamic changes in their medical visits in real time, adjust the hospital admission model , implement the graded treatment policy, and promote the prevention and control of respiratory diseases in children.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.
Humans ; Randomized Controlled Trials as Topic ; Acupuncture Therapy/methods* ; Pain ; Pain Management ; China

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.

The early response of plant auxin gene family Aux/IAA (auxin/indole-3-acetic acid) and its interaction with auxin response factor (ARF) are important pattern to regulate plant growth and development. This work identified 28 StoIAA and 24 StoARF members based on the whole genome data of the medicinal plant Senna tora L., which were classified into 10 and 8 subfamilies, respectively. Phylogenetic tree and collinearity analysis showed that S. tora has close evolutionary relationship with the IAA and ARF homologous genes of Glycine max, Medicago truncatula, and the segment duplication events dominate the expansion of StoIAA and StoARF. Gene structure analysis showed that the vast majority of StoIAA and StoARF contain characteristic conserved domain. Transcriptome data showed that StoIAAs and StoARFs were expressed in leaves, roots and seeds, some members had tissue specific expression. The StoIAA and StoARF promoter region most contain functional elements related to stress response, growth and development, hormone induction and secondary metabolism. In addition, gene expression analysis showed that many StoIAAs and StoARFs can quickly respond to drought and salt stress and exhibited same expression patterns under both stress condition. The yeast two-hybrid experiment confirmed that StoARF8 and StoARF10 exhibit varying degrees of interaction with multiple StoIAA proteins, respectively. The above results provide a basis for further biological functional analysis of the Aux/IAA and ARF gene family of S. tora.