ObjectiveTo observe the clinical efficacy and safety of Mailuoning compound solution in the treatment of hip joint pain via nerve blocks around the hip joint. MethodsFrom March 2015 to March 2019，a total of 136 patients with hip joint pain who met the inclusion criteria were admitted and divided into an observation group and a control group according to the random number table method. Among them，six cases fell off due to failure to complete five treatments，and finally， 130 patients entered clinical observation，with 65 cases in each group. The observation group used Mailuoning compound solution for nerve blocks around the hip joint（including obturator nerve，femoral nerve branch，superior gluteal nerve， and hip fascia）. The control used Mailuoning compound solution for a simple obturator nerve block. The differences in the visual analogue scale （VAS） and Harris score of hip joint of the two groups before and after treatment were observed. Any adverse drug reactions and adverse events during the treatment of the patients were recorded. ResultsThe VAS score of the two groups was significantly decreased after treatment （P<0.01）. The observation group had a more significant decrease compared to the control group（P<0.01）. The total Harris score of hip joint， pain degree，function score， and motion of joint of the two groups were significantly improved after treatment （P<0.01）. Compared with the control group，the improvement in the total Harris score of hip joint， pain degree，and function score was more significant in the observation group （P<0.01）. The clinical efficacy based on the Harris score of hip joint of the two groups was compared. The excellent and good rate of the observation group was 84.62% （55/65）， which was significantly better than that of the control group ［56.92% （37/65）］ （χ²=12.05，P<0.01）. The follow-up results showed that the patients who achieved excellent and good results had stable curative effects and low recurrence rates，and there was no significant difference in recurrence rate between the two groups. Case analysis showed that after treatment of femoral head necrosis，the saccular transparent shadow of the femoral head was significantly reduced，and the number of bone trabeculae increased. The low-density shadow decreased as can be seen on hip X-rays. In patients with hip osteoporosis after treatment，the number of bone trabeculae increased， and the low density shadow reduced. ConclusionThe use of Mailuoning compound solution for nerve blocks around the hip joint gives full play to the synergistic effect of Mailuoning compound solution and nerve block. It can effectively relieve hip joint pain，promote the recovery of hip joint function，reduce the disability rate，and improve the quality of life of patients. Early intervention is an important link in the treatment of hip joint pain diseases，which can effectively control the development of the patient's disease. Mailuoning compound solution is a new idea and method to treat hip joint pain through neuroregulation，which is easy to operate，with high safety and good therapeutic effect. In future studies，a larger sample size is needed，and more in-depth research should be conducted on the imaging changes and mechanisms of action for various hip joint pain diseases.

AIM:To investigate alterations in the expression levels of inflammatory cytokines and subsets of CD8+ T cells in the peripheral blood of patients with diabetic retinopathy(DR).METHODS:Retrospective study. A total of 40 patients with type 2 diabetes admitted to Xi'an People's Hospital(Xi'an Fourth Hospital)from April to July 2022 were recruited for this study and categorized into two groups: 20 cases in the simple type 2 diabetes mellitus(DM)group, and 20 cases in the DR group. Additionally, 20 healthy individuals undergoing routine physical examinations served as the control group. The expression levels of cytokines, including interleukin(IL)-6, IL-8, and IL-10 in peripheral blood were quantified using ELISA. Flow cytometry was employed to analyze the expression of programmed cell death-1(PD-1), T cell immunoglobulin domain and mucin domain protein-3(TIM-3), CD28, and CD57 on CD8+ T cells.RESULTS:The peripheral blood expression of IL-6, IL-8, and IL-10 inflammatory cytokines were significantly elevated in DR patients as detected by ELISA(all P<0.001); flow cytometry analysis showed that the expression of PD-1, TIM-3, and CD57 were elevated in peripheral blood CD8+ T cells of DR patients(all P<0.001), and the expression of CD28 was decreased(all P<0.001).CONCLUSION:In DR patients, CD8+ T cells may undergo depletion and senescence as a result of elevated pro-inflammatory cytokines, including IL-6, IL-8, and IL-10.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Objective To observe changes in genetic material in the peripheral blood of pediatric patients with vascular malformations after interventional procedures. Methods A total of 108 children with vascular malformations who underwent interventional procedures at Shandong University Affiliated Children’s Hospital between February 2021 and January 2024 were selected as the research subjects. Clinical data and peripheral venous blood samples before and after the interventional procedures were collected from the children. Two biological indicators, γ-H2AX and peripheral blood lymphocyte chromosomal aberration (CA), were used to determine the levels of genetic material damage in children with vascular malformations before and after interventional procedures. Results The median age of the children was 7 years and the median body weight was 27 kg. The median dose-area product (DAP) was 24.20 Gy·cm² and the median DAP/kg was 1.04 Gy·cm²/kg. The incidence rates of both γ-H2AX foci and CA in children with vascular malformations significantly increased after the interventional procedures (Z = 5.924, P < 0.001; Z = 8.515, P < 0.001). The incidence of postoperative CA in 7 children were significantly higher than that in others, approaching or exceeding 4%. The incidence rates of postoperative γ-H2AX foci and CA in children with DAP/kg ≥ 1 Gy·cm²/kg were significantly higher than those in children with DAP/kg < 1 Gy·cm²/kg (U = 7.586, P = 0.031; U = 6.835, P = 0.009). No significant differences were observed in the incidence rates of postoperative γ-H2AX foci and CA among subgroups based on age, body weight, or surgical site. A positive correlation was observed between the difference in the incidence rates of γ-H2AX foci before and after the procedure and DAP/kg (R = 0.493, P = 0.027). Conclusion Ionizing radiation exposure during interventional procedures can increase peripheral blood genetic material damage levels in children with vascular malformations, and the damage levels show a correlation with the radiation dose, with some children being abnormally sensitive. Further research is needed to explore the influencing factors for genetic material damage in children with vascular malformations after interventional procedures, which is of great significance for reducing long-term cancer risks and achieving personalized treatment strategies.

As a key member of the insulin-like growth factor family， insulin-like growth factor-‍Ⅰ （IGF-‍Ⅰ） is mainly synthesized in the liver and is widely distributed in the human body， and it is involved in the physiological processes such as cell proliferation， differentiation， metabolism， and apoptosis. Studies have shown that the level of IGF-‍Ⅰ is negatively correlated with the severity of liver cirrhosis， and IGF-‍Ⅰ mainly affects the progression of liver cirrhosis by inhibiting liver fibrosis， promoting DNA damage repair， and regulating lipid metabolism. Monitoring of IGF-‍Ⅰ level is expected to provide an evaluation indicator for improving the prognosis of patients with liver cirrhosis， and stimulating the action pathway of IGF-‍Ⅰ or regulating its expression level may become a new method for the treatment of liver cirrhosis. This article reviews the research advances in IGF-‍Ⅰ in liver cirrhosis， in order to provide new ideas for the diagnosis and treatment of liver cirrhosis.

Objective To study the effects of scutellarin on endometrial carcinoma Ishikawa cells,and analyze the correlation between the effects and phosphatidyl inositol 3 kinase(PI3 K)/protein kinase B(Akt)signaling pathway.Methods Ishikawa cells were divided into blank group and experimental-L,-M,-H groups,each group was treated with complete medium containing 0,5,10 and 20 μmol·L-1 scutellarin,respectively.Cell viability,clonal formation ability,metastatic ability,invasion,apoptosis and protein expression were detected by cell counting kit-8(CCK-8),plate cloning,scratch,Transwell,flow cytometry and Western blot assay,respectively.Results The cell viability of blank group and experimental-L,-M,-H groups at 48 h were(100.00±0.00)％,(78.51±7.54)％,(52.93±4.91)％and(41.62±5.33)％;the clone formation rate were(100.00±0.00)％,(56.59±6.34)％,(35.23±4.62)％and(10.66±1.91)％;the scratch healing rate were(53.70±6.19)％,(40.59±4.75)％,(34.25±4.40)％and(15.78±2.14)％;the number of invasive cells were 189.70±14.06,106.82±12.67,84.37±8.13 and 53.74±6.78;the relative expression levels of matrixmetallo proteinase-2 were 0.96±0.10,0.73±0.06,0.68±0.08 and 0.42±0.05;tissue inhibitor of MMP-1(TIMP-1)were 0.35±0.04,0.51±0.05,0.74±0.08 and 1.20±0.14;the apoptosis rates were(4.21±0.53)％,(15.83±2.42)％,(22.72±3.85)％and(34.41±4.67)％;the relative expression levels of B cell lymphoma-2(Bcl-2)were 1.38±0.15,0.90±0.10,0.56±0.06 and 0.24±0.03;Bcl-2 associated X protein(Bax)were 0.31±0.02,0.44±0.04,0.93±0.11 and 1.26±0.14;the relative expression levels of PI3Kp85 were 0.67±0.05,0.42±0.04,0.36±0.02 and 0.28±0.03;phosphorylated Akt(p-Akt)were 0.78±0.06,0.53±0.04,0.46±0.05 and 0.42±0.03.Compared with the blank group,the above indexes in the experimental-L,-M,-H groups were statistically significant(P＜0.05 or P＜0.01).Conclusion Scutellarin can inhibit the proliferation,metastatic ability and invasion of endometrial carcinoma Ishikawa cells and promote apoptosis by regulating PI3K/Akt signaling pathway.

Objective To investigate the therapeutic effect and mechanism of paeoniflorin(PAE)on thrombosis angiitis obliterans(TAO)in rats.Methods TAO rat model was established by sodium laurate injection.Rats were randomly divided into sham operation group(intraperitoneal injection of 0.9％NaCl),model group(intraperitoneal injection of 0.9％NaCl),experimental-L,-H groups(intraperitoneal injection of PAE 5,20 mg·kg-1·d-1),experimental-H+agonist group(intraperitoneal injection of 20 mg·kg-1·d-1 PAE+caudal vein injection of 10 ng·mL-1·kg 1·d-1 740 Y-P).Thrombin time(TT)was measured by magnetic bead coagulation;the levels of interleukin(IL)-1 β and endothelin 1(ET-1)were detected by enzyme-linked immunosorbent assay kit;the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated-PI3K(p-PI3 K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,p-NF-κB p65 were detected by Western blotting.Results The TT of sham operation group,model group,experimental-L,-H groups and experimental-H+agonist group were(14.88±1.32),(10.02±0.95),(12.65±1.22),(14.70±1.36)and(10.64±1.21)s;IL-1β were(154.23±13.45),(356.69±31.17),(268.62±23.58),(199.64±20.87)and(337.48±31.46)pg·mL-1;ET-1 were(6.78±0.68),(14.43±1.14),(11.23±1.07),(8.20±0.81)and(13.33±1.27)pg·mL-1;p-PI3K/PI3K were 0.36±0.04,0.76±0.07,0.59±0.05,0.44±0.04 and 0.69±0.07;p-AKT/AKT were 0.52±0.05,0.90±0.09,0.74±0.08,0.61±0.06 and 0.86±0.08;p-NF-κB p65/NF-κB p65 were 0.28±0.03,0.95±0.04,0.69±0.07,0.35±0.05 and 0.87±0.08,respectively.There were statistically significant differences between model group and sham operation group(all P＜0.05);the above indexes in experimental-L group and experimental-H group were significantly different from those in medel group(all P＜0.05);the above indexes in experimental-H+agonist group were significantly different from those in experimental-H group(all P＜0.05).Conclusion PAE may improve disease progression in TAO rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.

Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P＜0.05,P＜0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P＜0.05,P＜0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P＜0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.

Objective To establish a method for determination of aspirin(ASP)and salicylic acid(SA)in plasma of children with kawasaki disease by high performance liquid chromatography-isotope dilution mass spectrometry(HPLC-IDMS).Methods The samples were pre-treated by precipitation protein method with organic solvent.ASP-D4 and SA-D4 were used as isotope internal standards.Chromatographic column:Phenomenex Kinetex? XB C18(2.6 mm × 50.0 mm,3.0μm);flow phase:0.1％formic acid-water(A)and acetonitrile(B),gradient elution;flow speed:0.5 mL·min-1;injection volume:6 μL.The detection method of mass spectrometry was negative ion mode,multireaction monitoring mode for quantitative analysis.Results The linear range of aspirin was 1.02-4 000 ng·mL-1(r2=0.995 4),and lower limit of quantification(LLOQ)was 1.02 ng·mL-1.The linear range of salicylic acid was 1.28-5 000 ng·mL-1(r2=0.998 5),and LLOQ was 1.28 ng·mL-1.Accuracy,precision,matrix effect and stability were in line with the provisions of Chinese Pharmacopoeia(2020 edition).Conclusion This study determined the blood concentration of aspirin and salicylic acid in children with HPLC-IDMS,which is rapid,simple,stable,economical,and high specificity.It can be applied to therapeutic drug monitoring of aspirin and salicylic acid in clinical children with kawasaki disease.

Objective To investigate whether circular RNA(circRNA)circ_0054633 targets microRNA-375(miR-375)to regulate the oxidative damage of cardiomyocytes induced by hydrogen peroxide(H2O2).Methods H9C2 cardiomyocytes were divided into control group(normal culture without any treatment),hydrogen peroxide(H2 O2)group(150 μmol·L-1 H2 O2 treated cardiomyocytes for 6 h),H2O2+si-NC group,H2O2+si-circ_0054633 group,H2O2+miR-NC group,H2O2+miR-375 group,H2O2+si-circ_0054633+anti-miR-NC group,H2O2+si-circ_0054633+anti-miR-375 group(cardiomyocytes were transfected with si-NC,si-circ_0054633,miR-NC,miR-375 mimics,si-circ_0054633+anti-miR-NC,si-circ_0054633+anti-miR-375,respectively;24 h after transfection,cardiomyocytes were treated with 150 μmol·L-1 H2O for 6 h).Real-time fluorescence quantitative polymerase chain reaction was used to determine the expression of miR-375,the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)were determined by kit,apoptosis was determined by flow cytometry.Results The expression levels of miR-375 in cardiomyocytes of control group,H2O2 group,H2O2+si-NC group,H2O2+si-circ_0054633 group,H2O2+miR-NC group,H2O2+si-circ_0054633+anti-miR-NC group,H2O2+si-circ_0054633+anti-miR-375 group were 1.00±0.00,0.42±0.05,0.40±0.06,0.69±0.08,1.00±0.00,3.41±0.28,1.00±0.00 and 0.26±0.02,respectively;MDA contents were(3.19±0.32),(13.46±1.27),(15.39±1.04),(5.26±0.51),(16.05±1.36),(9.18±0.85),(4.89±0.44)and(10.05±0.92)nmol·L-1,respectively;SOD activities were(64.69±5.81),(18.23±1.33),(17.07±1.41),(55.74±5.13),(17.12±1.64),(47.66±4.59),(56.77±4.71)and(27.95±2.47)U·mL-1,respectively;the apoptosis rates were(6.21±0.59)％,(29.22±2.19)％,(30.94±2.85)％,(10.05±0.92)％,(31.14±2.83)％,(13.74±1.24)％,(10.39±0.88)％and(21.31±1.92)％,respectively.The above indexes of H2O2 group were compared with the control group,the above indexes of H2O2+si-circ_0054633 group was compared with the H2O2+si-NC group,the above indexes of H2O2+miR-375 group was compared with the H2O2+miR-NC group,the above indexes of H2O2+si-circ_0054633+anti-miR-375 group were compared with H2O2+si-circ_0054633+anti-miR-NC group,the differences were statistically significant(all P＜0.05).Conclusion Interfering with the expression of circ_0054633 can reduce the oxidative stress and apoptosis of cardiomyocytes induced by hydrogen peroxide by targeting miR-375,thereby protecting cardiomyocytes from oxidative damage.