Objective To construct programmed cell death protein-ligand 1(PD-LI)^hi tolerogenic dendritic cell (tol-DC) derived from bone marrow of DA rats and identify its immunological function. Methods DA rat bone marrow cells were extracted, combined with recombinant mouse granulocyte macrophage colony-stimulating factor and recombinant mouse interleukin (IL)-4, and cultured for 6 days in vitro to induce the differentiation of bone marrow cells into immature dendritic cells (imDC). Lipopolysaccharide was used to stimulate cell maturation and cultured for 2 days to collect mature dendritic cells (mDC). PD-L1 lentiviral vector virus stock solution or equivalent dose lentiviral stock solution was added, and PD-L1^hitol-DC and Lv-imDC were collected after culture for 2 days. The morphology of PD-L1^hitol-DC was observed by inverted phase contrast microscope and transmission electron microscope. Real-time fluorescence quantitative reverse transcription polymerase chain reaction, Western blotting and flow cytometry were used to detect the expression level of specific markers on cell surface. CD8⁺T cells derived from Lewis rat spleen were co-cultured with imDC, mDC, Lv-imDC and PD-L1^hitol-DC, respectively. The levels of inflammatory factors in the supernatant of each group were detected by enzyme-linked immunosorbent assay. The apoptosis of T cells and the differentiation of regulatory T cells (Treg) in each group were analyzed by flow cytometry. Results The morphology of PD-L1^hitol-DC modified by PD-L1 gene was consistent with tol-DC characteristics, and the expression levels of CD80, CD86 and major histocompatibility complex (MHC) on the surface were low. After mixed culture with CD8⁺ T cells, the levels of IL-10 and transforming growth factor (TGF) -β1 in the supernatant of PD-L1^hitol-DC group were higher, the levels of tumor necrosis factor (TNF) -α and IL-17A were lower, and the apoptosis of T cells and Treg differentiation were increased. Conclusions Overexpression of PD-L1 through lentiviral vectors may successfully induce the construction of bone-marrow derived PD-L1^hitol-DC in DA rats, promote the secretion of anti-inflammatory factors and T cell apoptosis, induce the differentiation of Treg, and inhibit the immune response of allogeneic CD8⁺T cells, which provides experimental basis for the next organ transplantation immune tolerance study.

PURPOSE: Hidden blood loss (HBL) during the perioperative period significantly impacts postoperative recovery and complications, yet it is frequently disregarded. This study aimed to investigate the effects of tip-apex distance (TAD) and calcar-referenced tip-apex distance (calTAD) on HBL in the treatment of intertrochanteric fractures utilizing proximal femoral nail antirotation (PFNA). The study also seeks to evaluate the possible decrease in HBL subsequent to PFNA treatment by optimizing nail positioning. METHOD: A historical cohort study was conducted from January 2020 to December 2022. Patients diagnosed with unilateral acute closed femoral intertrochanteric fracture and who underwent PFNA internal fixation surgery met the inclusion criteria, and were grouped according to the value of calTAD and TAD. The participants were divided into low TAD group (TAD<20 mm) and high TAD group (TAD≥20 mm); low calTAD group (calTAD<7.625 mm) and high calTAD group (calTAD≥7.625 mm), respectively. The primary outcome measures were intraoperative blood loss (including HBL, overt blood loss, and total blood loss). Continuous data were analyzed using an independent sample t-test or Mann-Whitney U test, and categorical data were analyzed using the Pearson Chi-square test. Univariate analysis was used to evaluate the association between various indicators and perioperative HBL. A stepwise multiple linear regression analysis model was used to determine the independent factors affecting perioperative HBL. A p value less than 0.05 was considered statistically significant. RESULTS: A total of 131 patients were initially included, of which 80 were assigned to the calTAD group (with 61 in the high calTAD group and 19 in the low calTAD group), and 80 were assigned to the TAD group (with 34 in the high TAD group and 46 in the low TAD group). The average HBL for the low TAD group was 772.85 mL, whereas for the high TAD group it was 919.68 mL (p>0.05). The average HBL for the low calTAD group was 611.42 mL, whereas for the high calTAD group it was 904.97 mL (p<0.05). Subsequent analysis revealed that the patient's height, preoperative hemoglobin levels, changes in hemoglobin and hematocrit levels from pre- to post-surgery, and calTAD are independent risk factors influencing HBL. CONCLUSION In summary, our investigation revealed a significant correlation between the positioning of nails in PFNA and HBL during the perioperative period. By optimizing the placement of the cephalic nail, specifically by ensuring a calTAD of less than 7.625 mm, a significant decrease in HBL can be attained. Additionally, we identified that height, preoperative hemoglobin, differences in preoperative and postoperative hemoglobin and hematocrit, and the positioning of the cephalic nail were independent risk factors for HBL.
Humans ; Retrospective Studies ; Male ; Blood Loss, Surgical/prevention & control* ; Female ; Hip Fractures/surgery* ; Aged ; Fracture Fixation, Intramedullary/methods* ; Bone Nails ; Perioperative Period ; Middle Aged ; Aged, 80 and over

Inflammatory bowel disease （IBD）， consisting of ulcerative colitis and Crohn's disease， is a chronic relapsing inflammatory gastrointestinal disease closely associated with immune dysfunction. The pathogenesis of IBD is closely related to genetic susceptibility， immune system dysfunction， environmental change， and intestinal microbial dysbiosis. Modern research has found that macrophage polarization plays an important role in the development of IBD and can affect the level of inflammatory response， intestinal mucosal repair， and intestinal microbial balance， making it a potential target for IBD treatment. Increasing evidence suggests that traditional Chinese medicine and its active components can regulate macrophage polarization through multiple pathways and balance the M1/M2 macrophage ratio， thus inhibiting inflammatory response， promoting intestinal mucosal repair， and slowing down the progression of IBD. This article summarized the biological processes and targets involved in macrophage polarization and discussed its impact on IBD. It also provided a brief overview of the latest research on how traditional Chinese medicine and its active components can improve IBD by regulating macrophage polarization， so as to provide new directions and strategies for the clinical application of traditional Chinese medicine in IBD treatment.

ObjectiveTo evaluate the efficacy and safety of Rongjin Tongbi decoction on sciatica caused by lumbar intervertebral disc herniation with liver and kidney deficiency type based on a randomized controlled study. MethodFrom January 2019 to July 2022， 90 patients in the department of Traditional Chinese medicine（TCM） of Beijing Jishuitan Hospital who met the inclusion criteria were selected and divided into two groups according to the random number table， with 45 patients in each group. During the study， 19 cases dropped out， with 41 cases included in the final observation group and 30 cases in the control group. The observation group was given Rongjin Tongbi decoction orally， and the control group was given Loxoprofen Sodium Tablets orally for 28 days. The differences in the visual analog scale （VAS） scores， the Japanese Orthopaedic Association （JOA） scores， activities of daily living （ADL） assessments， TCM clinical symptoms， subjective symptoms， and clinical signs scores between two groups before and after treatment were observed. Liver and kidney functions and gastrointestinal adverse reactions were detected for safety evaluation. ResultBefore treatment， there was no statistically significant difference in scores between the observation group and the control group. After treatment， the absolute values of the differences in VAS and ADL scores in the observation group were higher than those in the control group （P<0.05）. There was no statistically significant difference in the absolute value of the difference in JOA scores between two groups. The absolute value of the difference in TCM clinical symptom scores in the observation group was higher than that in the control group （P<0.01）. There was no statistically significant difference in the absolute values of the differences in subjective symptom and clinical sign scores between two groups. The levels of liver and kidney function indicators in both groups before and after the experiment were normal， and there was no significant difference in gastrointestinal reactions. ConclusionRongjin Tongbi decoction can significantly improve the symptoms of sciatica patients caused by lumbar intervertebral disc herniation with liver and kidney deficiency type. After treatment， the patients exhibited significant improvements in pain， activity and other aspects， and it is proven to be safe and reliable， which is conducive to the recovery of physical function.

Objective:To preliminarily explore the long-term improvement of low-frequency deep brain stimulation (DBS) on the nucleus basalis of Meynert (NBM) in cognitive disorders, neuropsychiatric symptoms and sleep disorders of patients with early-onset severe Alzheimer's disease (AD).Methods:A retrospective study was performed; 18 patients with early-onset severe AD admitted to Department of Neurosurgery, First Medical Center of PLA General Hospital from January 2016 to December 2022 were included. These patients were divided into NBM-DBS group and control group according to different treatments; 6 patients received low-frequency NBM-DBS on basis of conservative treatments; 12 patients accepted conservative treatments. Changes in Brief Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Hamilton Depression Rating Scale (HAMD), Becker-Lavanson Mania Scale (BRMS), Pittsburgh Sleep Quality Index (PSQI), and Zarit Caregiver Burden Interview (ZBI) were observed before treatment and 1 year after follow up.Results:MMSE and MoCA scores 1 year after follow up obviously reduced compared with those before treatment in both NBM-DBS and control patients; MMSE and MoCA scores in NBM-DBS patients showed no significant differences between 1 year after follow up and before treatment ( P>0.05), while significant differences were noted in the control group between 1 year after follow-up and before treatment ( P<0.05); and no significant differences in MMSE and MoCA scores were noted between the 2 groups 1 year after follow up ( P>0.05). NPI, HAMD, BRMS and ZBI scores in the NBM-DBS group 1 year after follow up were significantly different compared with those before treatment ( P<0.05); no significant differences were noted in NPI, HAMD and ZBI scores in the control group between 1 year after follow up and before treatment ( P>0.05), while significant difference was noted in BRMS scores ( P<0.05); significant differences in NPI, HAMD, BRMS and ZBI scores were noted between the 2 groups 1 year after follow up ( P<0.05). Conclusion:Low-frequency NBM-DBS is not only effective in improving cognitive disorders, but also effective in improving neuropsychiatric symptoms and sleep disorders, as well as reducing caregiver burden in patients with early-onset severe AD.

Objective To analyze the distribution of common allergens in children with allergic rhinitis(AR)in Hangzhou,and to provide reference for its prevention and treatment.Methods From January 2020 to December 2022,13 521 children who were diagnosed with AR and underwent in vitro serum specific immunoglobulin E(sIgE)detection in Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University were selected as the research objects.The positive rates of allergens in children with AR of different genders,ages and seasons were compared.Results Among 13 521 children,the positive rate of sIgE was 54.49%(7367/13 521),of which 64.82%were allergic to only one allergen.Among the 19 common allergens,the top three overall positive rates were household dust mite(44.27%),milk(14.62%),and mixed grass(4.82%).The positive rates of allergens of house dust mites,cat hair dander,mulberry,mold combination,tree pollen combination,amaranth,cockroach,milk,shrimp,crab,pineapple,shellfish and mango in male children were significantly higher than those in female children(P<0.05).The positive rates of allergens of house dust mite,mixed grass,cat hair dander,mulberry,mold combination,egg white,shrimp,crab,pineapple,cashew nuts and shellfish in different age groups were statistically significant(P<0.05).July and August were the two months with the highest allergen positive rate.The allergen positive rates of house dust mite,dog and cat hair dander were the highest in summer,and the allergen positive rate of plants was consistent with the flowering season.The sIgE concentration of house dust mite(77.87%)was mainly grade 3 and above.The sIgE concentration of other allergens was mainly grade 1 and 2.Conclusion Dust mites and milk are the most common allergens in children with AR in Hangzhou,and the distribution of allergens varies with gender,age and season.Allergen detection can provide a more accurate plan for the diagnosis,prevention and treatment of AR.

Objective To compare and analyze clinical effects of three correction methods in type Ⅲnipple retraction.Methods A total of 93 patients with type Ⅲ nipple retraction were retrospectively enrolled at Clifford Hospital between May 2018 and December 2023.Based on the different surgical methods employed,they were categorized into three groups:group A(silk traction method,n=30),group B(areola double-flap method,n=31),and group C(areola single-flap method,n=32).The study compared the operation time,therapeutic efficacy,hemodynamic disorders,improvement in nipple appearance and function,complications,patient satisfac-tion,and recurrence rates among these three groups.Results The operation duration was significantly longer in group B compared to groups A and C(P<0.05).Group C exhibited a significantly higher total response rate than groups A and B(P<0.05),while no significant difference was observed between groups A and B(P>0.05).There were no significant differences in the incidence of hemodynamic disorders among the three groups(P>0.05).The improvement scores for nipple appearance and function were significantly higher in group C compared to groups A and B(P<0.05),with no significant difference between groups A and B(P>0.05).The incidence of complications was lower,satisfaction was higher,both being statistically significant,in group C compared to groups A and B(P<0.05),but there were no significant differences in the incidence of complications or satisfaction between groups A and B(P>0.05).The recurrence rate was significantly lower in group B and group C than in group A(P<0.05).Conclusion The correction effect of the areola single-flap method is superior to that of the silk trac-tion method and areola double-flap method in patients with type Ⅲ nipple retraction,thereby enhancing clinical efficacy,patient satisfaction,nipple aesthetics,and functionality while reducing complications and recurrence rates.

Objective To analyze the differential expressed genes(DEGs)in the lung tissues of rat model of high altitude pulmonary edema(HAPE)by using microarray analysis in order to provide new clues for molecular mechanism of HAPE.Methods Healthy male SD rats(8 weeks old,weighing 200±20 g)were randomized into normoxia control(NC)group,lipopolysaccharide(LPS)group,hypoxia group and hypoxia+low-dose LPS(HL)group.The rats of the LPS group and HL group were injected with 0.1 mL 0.05％LPS per 100 g body weight,and those of the NC group and the hypoxia group were administered with an equivalent volume of normal saline.The rats of the hypoxia group and the HL group were housed in a hypobaric chamber simulating an altitude of 5 000 m,and those of the NC group and the LPS group were raised simultaneously outside of the chamber.The wet/dry mass ratio(WDR)of lung tissue and total protein content in bronchoalveolar lavage fluid(BALF)were measured,and the histopathological changes of lung tissue was observed using HE staining.The total RNA was extracted from the lung tissues,and the mRNA expression profile was obtained with Affymetrix microarray followed by Gene Ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis with Metascape(http://metascape.org).Results The rats of the HL group showed significant congestion,edema,and widened alveolar septa.Compared with the NC group,the HL group had significantly increased lung WDR(P＜0.01)and total protein content in BALF(P＜0.05).Gene expression analysis revealed that there were 79 genes up-regulated and 59 genes down-regulated in the hypoxia group,473 genes up-regulated and 695 genes down-regulated in the LPS group,and especially,669 genes up-regulated and 1 253 genes down-regulated in the HL group.GO and KEGG pathway analyses revealed that the upregulated genes in the HL group were mainly enriched in biological processes,such as cytokine mediated signaling pathways,response to IL-1,regulation of inflammatory response,as well as signaling pathways,including cytokine-cytokine receptor interactions,TNF,NF-κB,IL-17,complement and coagulation cascades,etc.The down-regulated genes were mainly enriched in biological processes,such as extracellular matrix organization,regulation of endothelial cell migration,cell substrate adhesion,as well as signaling pathways,such as focal adhesion,Wnt,cGMP-PKG,PI3K-Akt,Rap1,etc.The mRNA expression of NF-κB,TNF-α,IL-1βand IL-6 was significantly up-regulated in the lung tissue of the HL group(P＜0.01).Conclusion Hypoxia+low-dose LPS is an effective procedure to establish a reliable model for HAPE in rats.Hypoxia can significantly aggravate LPS-induced inflammation and immune response,enhance the expression of inflammatory mediators,and thus promote the pathogenesis of HAPE.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Osteoporosis is an important cause of bone weakness and susceptibility to fractures. Anti-osteoporosis drugs of Western medicine cannot reverse its progression， and can only reduce the loss of bone density； long-term use of them is accompanied by certain adverse reactions. Traditional Chinese medicine focuses on syndrome differentiation and holistic approach， which can make up for the shortcomings of Western medicine’s treatment. The mammalian target of rapamycin （mTOR） signaling pathway is involved in the growth， proliferation， and differentiation of bone cells， and is closely related to the occurrence and development of osteoporosis. In recent years， various traditional Chinese medicine monomers （such as flavonoids， polysaccharides， alkaloids， etc.） and traditional Chinese medicine formulas （such as Bushen huoxue decoction， Liuwei dihuang pills， Erzhi pills， etc.） have been proven to promote bone formation， inhibit bone resorption， enhance bone cell autophagy， and delay the progression of osteoporosis by regulating the mTOR signaling pathway. Therefore， the article summarizes the traditional Chinese medicine monomer and formula that intervene in the mTOR signaling pathway for the treatment of osteoporosis， in order to provide medication ideas for the traditional Chinese medicine treatment of osteoporosis.