Fibrosis, which is a manifestation of the physiological response to injury characterized by excessive accumulation of extracellular matrix components, is a ubiquitous outcome of the repair process. However, in cases of repetitive or severe injury, fibrosis may become dysregulated, leading to a pathological state and organ failure. In recent years, a novel form of regulated cell death, referred to as ferroptosis, has been identified as a possible contributor to fibrosis; it is characterized by iron-mediated lipid peroxidation. It has garnered attention due to the growing body of evidence linking ferroptosis and fibrogenesis, which is believed to be driven by underlying inflammation and immune responses. Despite the increasing interest in the relationship between ferroptosis and fibrosis, a comprehensive understanding of the precise role that ferroptosis plays in the formation of fibrotic tissue remains limited. This review seeks to synthesize previous research related to the topic. We categorized the different direct and indirect mechanisms by which ferroptosis may contribute to fibrosis into three categories: (1) iron overload toxicity; (2) ferroptosis-evoked necroinflammation, with a focus on ferroptosis and macrophage interplay; and (3) ferroptosis-associated pro-fibrotic factors and pathways. Furthermore, the review considers the potential implications of these findings and highlights the utilization of ferroptosis-targeted therapies as a promising strategy for mitigating the progression of fibrosis. In conclusion, novel anti-fibrotic treatments targeting ferroptosis could be an effective treatment for fibrosis.

Objective To explore the possible mechanism of Bushen Qiangjin capsule on synovitis and fibrosis in knee osteoarthritis(KOA).Methods In the animal experiment,the animal model of KOA was established by anterior cruciate ligament transection(ACLT).The rats were randomly divided into blank group,model group,Bushen Qiangjin capsule group and celecoxib capsule group.The levels of interleukin-1β(IL-1β)and IL-18 in serum of rats in each group were detected by ELISA,and the histopathological changes of synovium of rats in each group were observed by HE and Sirius red staining.Immunohistochemical staining was used to observe the expression of NLRP3,Caspase-1,GSDMD,TGF-β and COL1A1 in synovium of rats in each group.In the cell experiment,Lipopolysaccharide(LPS)combined with Adenosine triphosphate(ATP)was used to stimulate rat-FLS to simulate OA inflammatory environment and induce pyroptosis model.The cells were treated with Bushen Qiangjin capsule or MCC950,and the levels of IL-1β and IL-18 in the cell culture supernatant of each group were detected by ELISA;the localization and expression of NLRP3,Caspase-1 and GSDMD were observed by immunofluorescence staining;and the mRNA and protein expression of NLRP3,Caspase-1,GSDMD,TGF-β,COL1A1,PLOD2 and TIMP1 were detected by RT-qPCR and Western Blot,respectively.Results The results of animal experiment showed that compared with the model group,Bushen Qiangjin capsule could significantly reduce the score of synovial histomorphology of KOA rats(P<0.01);significantly reduce the levels of IL-1β and IL-18 in serum of KOA rats(P<0.01);also reduce the expression of NLRP3,Caspase-1,GSDMD,TGF-β and COL1A1 protein in synovium of KOA rats(P<0.05,P<0.01).The results of cell experiment showed that compared with the model control group,Bushen Qiangjin capsule could significantly reduce the levels of IL-1β and IL-18 in the supernatant of cell culture(P<0.01);significantly reduce the relative fluorescence expression of NLRP3,Caspase-1 and GSDMD(P<0.01),and significantly reduce the expression of NLRP3,Caspase-1,GSDMD,TGF-β,COL1A1,PLOD2,TIMP1 mRNA and protein(P<0.01).Conclusion Bushen Qiangjin capsule could improve KOA synovitis and fibrosis by inhibiting the activation of NLRP3 inflammasome and regulating FLS pyroptosis.

Objective:To construct a diagnostic prediction nomogram for antibody-mediated rejection (AMR) after kidney transplantation (KT) based upon peripheral blood gene expression profiling and preliminarily screening potential drugs for AMR.Methods:Seven large kidney transplant cohort datasets related to AMR were retrieved from the database of GEO. Differential expression analysis was utilized for identifying differentially expressed genes between AMR and normal recipients. Multiple machine learning algorithms of random forest (RF), extreme gradient boosting (XGB), support vector machine (SVM) and generalized linear model (GLM) were employed for constructing diagnostic models for AMR after kidney transplantation. Receiver operating characteristic (ROC) curve was plotted for comparing the accuracy of each model. The key genes of optimal model were integrated for creating a diagnostic prediction nomogram for AMR. Calibration curve and decision curve analyses were employed for evaluating the accuracy of nomogram. The differentially expressed genes from biopsy tissues of AMR recipients were uploaded to the database of CMap for identifying potential therapeutic drugs through screening Top 5 compounds with opposite expression patterns to AMR.Results:Seven genes of CXCL10, FCGR1B, GBP5, CD69, LY96, BCL2A1 and EVI2A were over-expressed in both peripheral blood and biopsy tissues of AMR recipients. There were statistically significant differences with recipients without AMR (FDR<0.05). The AMR diagnostic model based upon RF algorithm demonstrated the highest AUC value (0.904) among various machine learning algorithms. Its AUC values were 0.876 and 0.824 in external datasets of GSE50084 and GSE175718. As for the diagnostic prediction nomogram constructed through integrating five key genes of BCL2A1, CXCL10, FCGR1BP, CD69 & EVI2A from RF model, calibration curve indicated that the predicted outcomes of nomogram approximated actual outcomes. Decision curve indicated that net benefit rate of nomogram was higher than that of extreme curves over a wide range of horizontal axis. The predicted results of CMap suggested that Top 5 compounds were raltegravir, rilmenidine, hydrastine, metyrapone and valproic acid.Conclusions:The nomogram constructed based upon peripheral blood gene expression profiling demonstrates high accuracy and generalizability in the diagnosis of AMR. As predicted by CMap, raltegravir, rilmenidine, hydrastine, metyrapone and valproic acid may be potential therapeutic drugs for AMR.

ObjectiveTo explore the imbalance of paravertebral muscle group for patients with unilateral lumbar disc herniation. MethodsFrom January, 2022 to January, 2023, 30 patients with unilateral lumbar disc herniation (observation group) and 30 healthy people matching in general data (control group) were measured the tension and stiffness of multifidus and erector spinae with MyotonPRO, while the observation group was assessed with Visual Analogue Scale (VAS) for pain and Japanese Orthopaedic Association (JOA) score, and the time of disease was also recorded. ResultsThe mean of bilateral tension and hardness of multifidus and erector spinae was more in the observation group than in the control group (|t| > 5.407, P < 0.001), and the tension and hardness of multifidus and erector spinae of the affected side were more than those of the unaffected side in the observation group (|t| > 11.219, P < 0.001). The tension and hardness of multifidus and erector spinae of the affected side were positively correlated with VAS score (r > 0.942, P < 0.001), and negatively correlated with JOA score (|r| > 0.886, P < 0.001). ConclusionThe tension and hardness of multifidus and erector spinae of the affected side increase after unilateral lumbar disc herniation, resulting in asymmetry.

ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.

ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.

Objective To explore the effect of head acupuncturing therapy combined with massaging key head acupoints on language and cognitive function in children with autism.Methods 60 children with autism who visited the Department of Pediatric Rehabilitation of our hospital from January 2021 to June 2022 were selected as subjects,who were then randomly divided into the conventional group treated with the conventional rehabilitation training and the combination group treated with head acupuncturing therapy combined with massaging the key acu-points,apart from conventional rehabilitation training 30 cases in each group.The cognitive function,developmental status,and parental quality of life before and after the treatment were compared between the two groups,and so were the language function and safety.Results There were no significant differences in the scores by Autism Behavior Checklist(ABC)and Childhood Autism Rating Scale(CARS),adaptability scores,language scores,and individual-social interaction scores between the conventional group and the combination group before the treatment(P>0.05).After the treatment,the scores by ABC and CARS were significantly decreased in both groups,and the scores of the combination group were significantly lower than those in the conventional group(P<0.05);The adaptability scores,language,individual-social interaction scores were significantly increased in both groups,and the scores of the combined group were significantly higher than those of the conventional group(P<0.05).The abnormal rates of symbolic expression,language comprehension,action-oriented subjects,and language development delay in the combined group were all significantly lower than those in the conventional group(P<0.05).There was no significant difference in the scores by the QL-Index between the conventional group and the combined group before the treatment(P>0.05),but after the treatment,the QL-Index scores of the conventional group and the combination group were increased,and the score of the combination group was significantly higher than that of the conventional group(P<0.05).The results of blood routine,urine routine,stool routine,liver function,and kidney function in both groups were not significantly abnormal.There was one case of mild swelling and pain at the acupunctured site in the combination group,which was improved without intervention.Conclusion Head acupuncturing therapy combined with massaging the key head acupoints can improve language function,cognitive function,and development of autis-tic children.In addition,it can enhance parental quality of life and have a high level of safety.

Objective:To explore the application value of guide tube fenestration and drainage technology in intracranial artery stenting surgery.Methods:A total of 120 patients with symptomatic intracranial atherosclerotic stenosis admitted to the Xingtai Third Hospital from January 2021 to December 2022 were selected and randomly divided into an observation group ( n=60) and a control group ( n=60). Both groups were treated with intracranial artery stenting, with the observation group receiving guidance catheterization and window opening technique during the surgery. Two groups of surgeries were observed and compared: the degree of vascular stenosis before and after surgery, the Montreal Cognitive Assessment Scale (MoCA) scores before and one month after surgery, intraoperative complications, and prognosis. Results:The surgical time and catheter placement time in the observation group were (110.20±23.32)minutes and (11.32±2.01)minutes, respectively, which were significantly shorter than those in the control group (all P<0.05). The stent placement rate and operation success rate in the observation group were 95.00% and 96.67%, respectively, significantly higher than those in the control group (all P<0.05). The degree of postoperative vascular stenosis in the observation group was (32.29±7.11)%, significantly milder than that in the control group [(44.43±8.15)%, P<0.05]. One month after surgery, the MoCA scores of both groups improved significantly compared to before surgery (all P<0.05), and there was no statistically significant difference between the groups ( P>0.05). There was no statistically significant difference in the incidence of collateral circulation occlusion and vascular rupture between the two groups (all P>0.05). During the follow-up period, there was no statistically significant difference in the incidence of restenosis, intracranial hemorrhage, and recurrent ischemic stroke between the observation group and the control group (all P>0.05); The good prognosis rate of the observation group was 73.33%, significantly higher than that of the control group (53.33%, P<0.05). Conclusions:The application of guided catheter fenestration technique in intracranial artery stenting has good value, which is beneficial for improving the stent placement rate and operation success rate, and improving the degree of vascular stenosis.

Objective:To explore the regulatory effects of cow milk with the addition of breast milk equivalent dose of somatostatin (SST) and motilin (MTL) on food allergy and food intolerance.Methods:Young Brown Norway (BN) rats were divided into 5 groups and fed with pure breast milk(breast milk group), cow milk(cow milk group), cow milk added with SST(SST group), cow milk added with MTL(MTL group) and cow milk added with both SST+ MTL(SST+ MTL group). Allergic irritation was enhanced with skin smear at the same time.Clinical damages were quantified weekly.Levels of serous total Immunoglobulin E (IgE) and fecal calprotectin (FC) were detected by the enzyme-linked immunosorbent assay (ELISA). Gastric emptying ratio and intestinal propulsion ratio were measured by method of dextran blue.Results:In breast milk group, cow milk group, SST group, MTL group and SST + MTL group, the levels of IgE were (45.75±5.05) μg/L, (580.42±45.24) μg/L, (290.38±22.88) μg/L, (424.26±22.17) μg/L, (209.49±17.59) μg/L, respectively; FC level were (149.07±24.78) μg/g, (458.85±33.81) μg/g, (343.63±34.97) μg/g, (407.79±29.62) μg/g, (296.83±28.77) μg/g, respectively; the total score of clinical damage were (0.50±0.61) scores, (9.37±1.04) scores, (6.83±1.49) scores, (7.00±1.14) scores, (5.37±1.19) scores, respectively.The cow milk group had the highest scores of clinical damages.Compared with the cow milk group, the clinical damage score, IgE and FC of the SST, MTL and SST+ MTL groups had significantly lower levels, and there was significant difference among them (all P<0.01). The general status of the SST + MTL group was most similar to the breast milk group.The gastric emptying rate of MTL group was the closest to that of breast milk group [(92.52±6.27)% vs.(100.00±9.70)%, P<0.05]. There were obvious diarrhea and fast small intestinal propulsion in cow milk group, the small intestinal propulsion ratio in breast milk group was (39.32±2.61)%, and (71.96±4.43) % in cow milk group, the difference was statistically significant between the 2 groups ( P<0.01). The intestinal motility of SST+ MTL group was decreased, but it just prevented diarrhea caused by milk allergy, the small intestine propulsion ratio in SST+ MTL group was (38.90±2.65)% vs.breast milk group (39.32±2.61)%( P>0.05). Conclusions:The cow milk added with SST and MTL decreased allergic reaction and increased food tolerance in gastrointestinal tract, which was more similar to breast milk.SST was beneficial to relieving allergic immune reaction, MTL contributed to improving the gastrointestinal tolerance of cow milk.The combination of SST and MTL may achieve an antagonistic and balanced mechanism on gastrointestinal regulation, which could synergistically improve the gastrointestinal tolerance of cow milk.

OBJECTIVE：To investigate the accessibility of antibiotics in essential medicine list in medical institutions of Nanjing area ，and to provide reference for formulating and improving related drug policy. METHODS ：Taking the original and imitated drugs as the objects of investigation ，the standard investigation method jointly formulated by WHO/HAI was adopted to select 35 kinds of antibiotics which were included in Essential Medicine List （2018 edition）and International Drug Price Indicator Guide（2015 edition），and to investigate 3 dimenions such as the availability （proportion of institutions that could provide this drug），price（calculated by MPR ）and affordability （the ratio of drug expenditure to the daily minimum wage of non-technical government workers ）of them in 13 second-class or above medical institutions in Nanjing area by online questionnaires during Jan.-Jun. 2019，so as to put forward the suggestions for drug policy formulation. RESULTS ：The median availability of original drugs was 0，with a range of 0 to 100％；the median availability of generic drugs was 30.80％，with a range of 0 to 100％. The median MPR of original drugs was 5.54，with a range of 1.96 to 18.83；the median MPR of generic drugs was 1.76，with a range of 0.16 to 7.66. Median affordability of original drugs was 8.68，with a range of 1.19 to 41.79；the median affordability of generic drugs was 0.52， with a range of 0.03 to 16.80. CONCLUSIONS：Generic drugs are more available than the originals. The price of original drugs is generally very high ， while the price of generic drugs is mostly cheaper. The affordability of original drugs is really poor ， and the 规。E-mail：shaorong118@163.com affordability of generic drugs is totally good. There are stillrooms for further improvement in the overall accessibility of essential medicines. At present ，ensuring the accessibility of original drugs may be more helpful to meet the needs of treatment. It is suggested to update and adjust the essential medicine list based on the clinical medication requirement ，popularize the knowledge about essential medicines ，properly adjust the price of original drugs and ease the treatment burden of patient. It is supposed to take into full consideration about the regional factors and the needs of different medical institutions when making drug policy.