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.

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.

OBJECTIVE: To evaluate the early efficacy of local application of tranexamic acid on the osteotomy surface during hallux valgus surgery in reducing postoperative occult blood loss and thus postoperative swelling. METHODS: The data of 40 cases with hallux valgus osteotomy admitted to the Department of Foot and Ankle Surgery of Jishuitan Hospital from July 11, 2022 to October 8, 2022, including 5 males and 35 females were retrospectively analyzed. According to the inclusion and exclusion criteria, 32 cases were finally divided into 16 cases in the observation group (application of tranexamic acid) and 16 cases in the control group (no application of tranexamic acid). The observation group was paired with the control group one by one in accordance with the operation style, and the change in the anterior and posterior diameter of the first metatarsal head, the change in the circumferential diameter of the foot, the length of the first metatarsal midline and the length of the plumbline of the foot measured by postoperative CT were compared between the two groups before and after surgery, in order to evaluate the degree of swelling around the incision after the surgery. The first metatarsal midline and plumb line were measured by reference to the two auxiliary lines that intersect the soft tissue border in the sesamoid bone position to measure the rotation angle of the first metatarsal. A total of three clinicians completed the measurements of these two line segments and interobserver comparisons were performed. RESULTS: By interobserver comparison, the consistency of the length of the midline of the first metatarsal and the plumbline measured by CT was high and could be considered a reliable measurement. After the paired t-test, there was no statistical difference in the amount of changes in the anteroposterior diameter of the first metatarsal before and after surgery between the observation and control groups (P>0.05), and the amount of changes in the circumferential diameter of the foot before and after surgery was smaller in the observation group than in the control group, which was statistically significant (P < 0.05); the length of the midline of the first metatarsal and the plumbline of the foot measured by CT after surgery was smaller in the observation group than in the control group, which was statistically significant (P < 0.05). CONCLUSION Local application of tranexamic acid on the osteotomy surface during hallux valgus osteotomy can relieve postoperative swelling to some extent, which may be related to the fact that tranexamic acid reduces occult blood loss in the postoperative period.
Humans ; Hallux Valgus/surgery* ; Tranexamic Acid/administration & dosage* ; Female ; Male ; Osteotomy/adverse effects* ; Retrospective Studies ; Edema/etiology* ; Adult ; Middle Aged ; Postoperative Complications/prevention & control* ; Antifibrinolytic Agents/administration & dosage*

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*

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.

BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

BACKGROUND:Exercise is an effective method for preventing and treating osteoporosis,but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE:To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats,and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS:A rat model of postmenopausal osteoporosis was established,and a 24-week moderate-intensity exercise was used for intervention.After the experiment,serum estradiol levels were measured by ELISA,and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT.The biomechanical indicators of the tibia were tested by a three-point bending test.Autophagosomes were observed by transmission electron microscopy.The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION:The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group(P＜0.01).The body mass of rats in each group increased,and the order was the ovariectomized group＞the ovariectomized+exercise group＞the sham-operation group＞the sham-operation+exercise group.The bone mineral density and bone mass of rats in all groups significantly increased(P＜0.01),but the increase in the ovariectomized group was significantly lower than that of the other groups,and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group.Compared with the sham-operation group,the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased(P＜0.01),while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased(P＜0.01).Compared with the ovariectomized+exercise group,the ovariectomized group showed significantly lower bone volume fraction,number of trabeculae,and bone mineral density of cancellous bone(P＜0.05),extremely significantly lower trabecular thickness(P＜0.01),and significantly higher mean trabecular pattern factor,trabecular separation,and structural model index(P＜0.01).Compared with the ovariectomized group,the LC3-Ⅱ/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group(P＜0.05).Compared with the sham-operation and ovariectomized groups,the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups,respectively.To conclude,moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels.

BACKGROUND:Currently,the verification of the precision of personalized bone models is usually performed by methods such as paired t-tests or intraclass correlation coefficient,but such methods often require the production of large batches of models,which do not satisfy the need for immediate use of personalized models. OBJECTIVE:To study the feasibility of establishing the equivalent model to verify the precision of the personalized bone model rapidly. METHODS:Bone CT images of three adults were randomly obtained for reconstruction.3D printing was used to create personalized bone models,and then the personalized bone models were scanned using CT and reconstructed.Mimics was used to compare the reconstructed models of bone CT images with the bone CT images.Geomagic Studio was used to analyze the fitting deviation between the reconstruction model of personalized bone model CT image and the reconstruction model of skeletal CT image.The 3D-printed personalized bone model was measured against the measurement positions and dimensions marked on the reconstruction model of skeletal CT image,and the error was calculated. RESULTS AND CONCLUSION:(1)By comparing the reconstructed bone CT image model with the bone CT scan image,the two were compatible in terms of anatomical structure and morphology,and the contours almost overlapped.(2)By fitting bias analysis,the standard bias was 0.176,0.226,and 0.143 mm in order,and all the results were<0.25 mm.(3)By measuring and calculating the model,the mean relative errors were 0.44%,0.21%,and 0.13%,and all the results were within 5%error.(4)The constructed equivalent model was in line with the basic conditions for making personalized bone models.The established equivalent model met the clinical needs and design requirements,and it was feasible to use the method of the equivalent model to verify the precision of the personalized bone model quickly.(5)This method could provide a targeted and rapid way to verify the precision of personalized bone models.It could achieve the goal of providing immediate clinical use without the need to produce large batches of models compared to conventional methods such as paired t-tests or intraclass correlation coefficient.

Objective To discuss the application effect of using a stone extractor balloon catheter to assist in crossing the anastomotic stenosis in treatment of anastomotic biliary stenosis after liver transplantation using endoscopic retrograde cholangiopancreatography(ERCP).Methods Clinical data of 48 patients who developed anastomotic biliary stenosis after liver transplantation and underwent ERCP treatment were collected.Upon unsuccessful use of a dilation catheter to cross the stricture,attempts were made to cross the anastomotic biliary stenosis by using a stone extractor balloon catheter.The success rate of the procedure was recorded,intraoperative conditions were observed,treatment outcomes and complications were analyzed.Results The main presenting symptoms in the 48 patients on admission were abdominal discomfort(32 patients),fever(7 patients),pruritus(4 patients),jaundice(3 patients),and no obvious symptoms(2 patients).Preoperative magnetic resonance cholangiopancreatography(MRCP)examination revealed isolated stricture of the anastomotic site in 35 cases,and stricture associated with stones in 13 cases.Using the stone extractor balloon catheter as a guide,guidewire crossing of the anastomotic stenosis was successful in 26 cases,resulting in a success rate of 54.17%(26/48).Through statistical analysis of the successful group and the failed group,there was a significant difference in whether the distal biliary dilatation between the two groups,and the difference was statistically significant(χ2 = 8.39,P = 0.004).In the 26 successfully treated cases,alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),and total bilirubin(TBiL)levels decreased significantly 48 hours after the procedure(P<0.05),and no serious complications occurred.Conclusion The use of a stone extractor balloon catheter significantly increases the success rate of crossing anastomotic stenosis in the treatment of anastomotic biliary stenosis after liver transplantation,especially in cases with distal dilatation of the common bile duct.This approach is safe and worth promoting.