Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

ObjectiveTo evaluate the clinical efficacy and safety of Huaban Jiedu Formulation （化斑解毒方， HJF） in treating psoriasis vulgaris with blood-heat syndrome. MethodsA randomized， double-blind， placebo-controlled study was conducted with 60 patients diagnosed with psoriasis vulgaris of blood-heat syndrome. Patients were randomly assigned to either a treatment group or a control group， with 30 cases in each. The treatment group received HJF granules orally， one dose a day， combined with topical Qingshi Zhiyang Ointment （青石止痒软膏）， while the control group received placebo granules， one dose a day， combined with the same topical ointment. Both groups were topically treated twice daily of 28 days treatment cours. Psoriasis area and severity index （PASI）， visual analogue scale for pruritus （VAS）， traditional Chinese medicine （TCM） syndrome scores， dermatology life quality index （DLQI）， and psoriasis life stress inventory （PLSI） were assessed before treatment and on day 14 and day 28. Response rates for PASI 50 （≥50% reduction） and PASI 75 （≥75% reduction）， as well as overall clinical efficacy， were compared between groups. Serum levels of interleukin-6 （IL-6） and interleukin-17 （IL-17） were measured before and after 28 days of treatment. Adverse reactions during treatment were recorded. ResultsAfter 28 days of treatment， both groups showed significant reductions in PASI total score， lesion area score， erythema， scaling， and infiltration scores， pruritus VAS score， TCM syndrome score， DLQI， PLSI， and serum IL-6 and IL-17 levels （P＜0.05）. Compared to the control group， the treatment group had significantly greater improvements in PASI total score and erythema score， TCM syndrome score， serum IL-6 and IL-17 levels， and PASI 50 response rate after 28 days （P＜0.05）. Between-group comparisons of score differences before and after 28-day treatment revealed that the treatment group showed significantly better improvements in PASI total， lesion area score， erythema score， TCM syndrome score， DLQI， PLSI， and inflammatory markers （P＜0.05 or P＜0.01）. The total effective rate on day 14 and day 28 was 40.00% （12/30） and 83.33% （25/30） in the treatment group， versus 6.90% （2/29） and 41.38% （12/29） in the control group， respectively. The clinical efficacy in the treatment group was significantly superior to that in the control group （P＜0.05）. Mild gastric discomfort occurred in 3 patients in the treatment group and 1 in the control group. ConclusionHJF can effectively improve skin lesions and TCM symptoms relieve pruritus， enhance quality of life， and reduce inflammatory markers IL-6 and IL-17， in patients with blood-heat syndrome of psoriasis vulgaris， with a good safety profile.

ObjectiveTo explore the possible action mechanism of Qingshi Anti-itch Ointment （青石止痒软膏， QAO） in the treatment of psoriasis. MethodsForty mice were randomly divided into four groups， blank group， model group， calcipotriol group and QAO group， with 10 mice in each group. Except for the blank group， psoriasis was induced by applying imiquimod cream to the dorsal skin. After modeling for 6 hours daily， the calcipotriol group and QAO group were treated with 0.5 g of calcipotriol ointment or 0.5 g of QAO， respectively， applied to the treated dorsal skin. The blank group and the model group received no treatment. The skin lesions were observed， and the psoriasis area and severity index （PASI） score was assessed every other day. After 7 days， Hematoxylin and Eosin （HE） staining was performed on dorsal skin tissue to observe pathological changes. The levels of interleukin 1β （IL-1β） and interleukin 18 （IL-18） were determined by enzym-linked immunosorbent assay （ELISA）. The protein levels of Caspase-1，Pro-Caspase-1， gasdermin D （GSDMD） and gasdermin-D-N （GSDMD-N） were detected by Western Blot （WB）. The protein levels of GSDMD were observed by immunohistochemistry. ResultsCompared with the blank group， the model group mice showed redness， erythema， and white scales on their skin， with histological observations indicating epidermal thickening， elongated spines， and infiltration of inflammatory cells. The PASI scores of the skin tissue on days 1， 3， 5， and 7 were elevated； the IOD and AOD values of GSDMD protein increased； the protein levels of Caspase-1， Pro-Caspase-1，GSDMD， GSDMD-N， and IL-1β and IL-18 were significantly elevated （P＜0.05 or P＜0.01）. Compared with the model group， the QAO group and calcipotriol group showed lighter skin lesions； the PASI scores on day 5 and day 7 in the QAO group， and on day 3， 5， and 7 in the calcipotriol group， were reduced； the IOD and AOD values of GSDMD protein， and the protein level of Caspase-1， GSDMD， and GSDMD-N， as well as level of IL-18 and IL-1β decreased in both groups； in the calcipotriol group， Pro-Caspase-1 protein level also decreased （P＜0.05 or P＜0.01）. Compared with the calcipotriol group， the QAO group showed slightly redder skin， more obvious thickening of the stratum corneum， and less capillary dilation； the PASI scores on day 3 and day 7 increased， while the score on day 5 was reduced； the protein level of Pro-Caspase-1， GSDMD， GSDMD-N， and the level of IL-18 and IL-1β were increased in the QAO group （P＜0.05）. ConclusionQAO can effectively relieve psoriasis dermatitis in mice. Its potential mechanism may be related to the regulation of the Caspase-1/GSDMD protein pathway， down-regulation of IL-18 and IL-1β levels， and alleviation of pyroptosis.

Objective: To explore the effects of sleep on subsequent day physical activity (PA) in children and adolescents, so as to provide a reference for refining PA intervention strategies and further investigating their underlying mechanisms. Methods: Through searching databases including Web of Science Core Collection, PubMed, EBSCOhost, ScienceDirect, Cochrane Library, CNKI, Wanfang and VIP cross sectional, cohort and experimental studies on sleep and subsequent day PA among children and adolescents were identified, with the searching period spanning from database inception to June, 2025. Based on the characteristics of the included literature, two sleep variables[sleep duration (SD) and sleep efficiency (SE)] and three physical activity variables[moderate to vigorous physical activity (MVPA), light physical activity (LPA), and total physical activity (TPA)] were selected. The relationship between these two types of variables was analyzed for pooled effect sizes using Stata 17.0. Results: A total of 14 studies were included, with 64.3% published in 2018 or later, involving 11 361 children and adolescents from 17 countries. Meta analysis results showed that both SD ( ES=0.04, 95%CI =0.01-0.07) and SE ( ES=0.24, 95%CI =0.01-0.47) were positively correlated with subsequent day MVPA (both P <0.05). However, no statistically significant associations were found with LPA ( ES=-0.04, 95%CI =-0.13 to 0.06; ES=-0.02, 95%CI =-0.15 to 0.11) or TPA( ES=0.09, 95%CI =-0.02 to 0.20; ES=0.02, 95%CI = -0.03 to 0.06)(all P >0.05). Subgroup analysis revealed that in the "≤6 years" subgroup, SD and SE were positively correlated with TPA ( ES=0.22, 95%CI =0.09-0.35) and MVPA ( ES=1.19, 95%CI =1.06-1.32), respectively; in the "6-12 years" subgroup, SD was positively correlated with MVPA ( ES=0.05, 95%CI =0.02-0.08); in the "≥12 years" subgroup, SE was positively correlated with LPA ( ES=0.08, 95%CI =0.00-0.16), while SD was negatively correlated with LPA ( ES=-0.23, 95%CI = -0.31 to -0.16) (all P <0.05). Conclusion Adequate SD and good SE can effectively enhance subsequent day MVPA among children and adolescents, although these sleep effects vary by age group.

Objective:To evaluate the early-to-mid-term efficacy of supramalleolar osteotomy (SMO) in the treatment of traumatic ankle arthritis secondary to peri-ankle fracture.Methods:A retrospective study was conducted to analyze the clinical data of 29 patients who had been treated for traumatic ankle arthritis secondary to old peri-ankle fracture by SMO from March 2018 to March 2023 at Department of Foot and Ankle Surgery, Beijing Jishuitan Hospital. There were 14 males and 15 females, 39.0 (25.0, 49.0) years in age. Types of old fracture: 4 lower tibiofibular fractures, 19 ankle fractures, and 6 pilon fractures. Surgery was conducted for 16 cases and conservative treatment for the remaining 13 cases. The interval between the old fracture and the current surgery was 10.0 (2.0, 19.5) years. The clinical efficacy was evaluated using the ankle-hindfoot score of American Association of Foot and Ankle Surgery (AOFAS), foot function index (FFI), and visual analog scale (VAS) pain score. Imaging analysis was conducted and imaging comparisons were made between pre-surgery and post-surgery in terms of tibial anterior surface (TAS) angle, tibial lateral surface (TLS) angle, talar tilt (TT) angle, and changes in modified Takakura staging. Complications were recorded. Surgical satisfaction was investigated at the final follow-up.Results:The 29 patients were followed up for 17.0 (14.0, 23.5) months. The AOFAS ankle-hindfoot score [(84.2±9.6) points], FFI [7.0 (3.0, 10.9) points], VAS pain score [2.0 (1.0, 3.0) points], and TAS angle [90.84° (86.70°, 92.50°)] at the final follow-up for all patients were significantly better than the pre-surgery values [(68.0±16.7) points, 20.9 (6.1, 29.1) points, 5.0 (2.0, 8.0) points, and 78.63° (74.30°, 85.00°)] (all P<0.05). At the final follow-up, the ankle arthritis grading did not show any significant change ( P>0.05) and there were no significant differences in TT angle or TLS angle between pre-surgery and post-surgery ( P>0.05). Incision failed to heal in 1 case, incision healing was delayed in 3 cases, and ankle arthritis progressed on imaging in 6 cases. As for patient self-assessed satisfaction, 23 cases felt very satisfactory, 4 cases quite satisfactory, and 2 cases common, giving an overall satisfaction rate of 93.1% (27/29). Conclusions:SMO has led to good early-to-mid-term efficacy in the treatment of traumatic ankle arthritis secondary to peri-ankle fracture, showing obvious pain relief and functional improvement after correction of the ankle joint alignment, limited postoperative complactions and a high rate of patient satisfaction.

Objective:to investigate the expression of integrin αvβ3 and osteopontin(OPN)in decidual tissues in missed abortion women with polycystic ovarian syndrome(PCOS).Methods:PCOS women with missed abor-tion(PCOS missed abortion group),non-PCOS with missed abortion(non-PCOS missed abortion group)and women with normal early pregnancy induced abortion(normal control group)who were admitted to the First Affili-ated Hospital of Xi'an Jiaotong University from February 2018 to December 2022 were selected as participants,and 20 subjects in each group.The expressions of integrin αvβ3 and OPN in decidual tissues among the three groups were detected.Correlation analysis was conducted between the expression levels of integrin αvβ3 and OPN in PCOS patients with missed abortion.Results:Integrin αvβ3 and OPN were mainly expressed in the epi-thelial cells of the uterus,as well as in decidual cells.There were significant differences in the positive rates and IHC scores of integrin αvβ3 and OPN in decidual tissues among the three groups(P<0.05).The positive rates and IHC scores in PCOS missed abortion group were significantly lower compared with non-PCOS missed abor-tion group and normal control group,and the difference was statistically significant(P<0.05),but there was no significant difference between non-PCOS missed abortion group and normal control group(P>0.05).The integrin αvβ3 and OPN in decidual tissues were mainly co-located in uterine epithelial cells.There were significant differ-ences in immunofluorescence intensity of integrin αvβ3 and OPN among the three groups(P<0.05).The missed abortion group of PCOS was significantly lower than that of non-PCOS missed abortion group and normal control group,and the difference was statistically significant(P<0.01).No significant difference was found between non-PCOS missed abortion group and normal control group(P>0.05).There were significant differences in the protein expression levels and mRNA expression levels of integrin αvβ3 and OPN in decidual tissue among the three groups(P<0.05).PCOS missed abortion group was significantly lower than non-PCOS missed abortion group and normal control group,and the difference was statistically significant(P<0.01).There was no significant difference between non-PCOS missed abortion group and normal control group(P>0.05).The results of Pearson correlation analysis showed that the protein and mRNA expression levels of integrin αvβ3 and OPN in decidual tis-sue of PCOS patients with missed abortion were significantly positively correlated(r>0,P<0.01).Conclusions:The integrin αvβ3 and OPN were expressed in both epithelial cells of the uterus and decidual cells in early preg-nancy.The expressions of them were significantly decreased in decidual tissues of PCOS patients with missed a-bortion,which might be related to reduced endometrial receptivity.The role of integrin αvβ3 and OPN in the occur-rence of missed abortion needs further study.

Objective:By comparing the effects of installing 3d-printed bolus with or without positioning holes on the skin fit and patient dose distribution,the advantages and disadvantages of the two installation methods in the application of radiotherapy after radical breast cancer surgery were evaluated,and the reference was provided for clinical application.Methods:A total of 48 patients(34 patients with and 14 patients without positioning holes)who received radiotherapy for breast cancer in Suining Central Hospital from December 2022 to Au-gust 2024 were randomly selected.Three dimensional reconstruction of the air gap between the patient body surface and the 3d-printed bolus was conducted,and the tissue dose distribution of each case was analyzed.Comparative analysis was conducted using t-test to ana-lyze the differences of the skin fit and the key dosimetric indexes of target areas and organs at risk between the two bolus installation meth-ods.Results:The mean values of the maximum air gap height,air gap area and air gap volume of the group with positioning holes were lower than those of the group without positioning holes(P<0.05),and the skin fit showed better consistency.The target area conformity in-dex(CI),homogeneity index(HI),and affected lung radiation acceptance(V20,V5)of patients with positioning holes were better than those of patients without positioning holes(P<0.05).There was no significant difference in target area coverage of prescription dose,cardiac dose Dmean and spinal cord dose Dmax between two groups(P>0.05).Conclusions:The skin fit,dosimetric indexes of patient target area and or-gans at risk of 3d-printed bolus with positioning holes were superior to those without positioning holes,showing significant advantages in clinical applications.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.