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 verify the feasibility of using a homemade lung phantom for quality control of Cyberknife by comparing the measurement results of the homemade lung phantom and CIRS dynamic phantom in E2E testing of Cyberknife lung tracking.  Methods　 : The patient treatment process was simulated, including CT positioning, plan design, irra- diation implementation, film scanning, and analysis using the homemade phantom and CIRS phantom. The two phantoms were measured five times using MLC under the S7 generation Cyberknife and five times using Iris under the M6 generation Cyberknife. The differences in measurement results between the two phantoms were analyzed using independent sample t-test. Results　: For the S7 generation Cyberknife, the statistical analysis of differences between the two phantoms in the detection values on the X-axis, Y-axis, Z-axis, and total deviation showed P values of 0.236, 0.175, 0.289, and 0.668, respect- ively. For the M6 generation Cyberknife, the statistical analysis showed P values of 0.880, 0.891, 0.573, and 0.433, respect- ively. The P values were all > 0.05. Therefore, there were no statistically significant differences in the detection results between the homemade lung phantom and the CIRS phantom under the S7 and M6 generation Cyberknife. The total deviation values were <1.5 mm. Conclusion　 The homemade lung phantom and CIRS phantom have consistent measurement results in the E2E testing of Cyberknife lung tracking and meet the requirements of Report of AAPM TG-135 and WS 667- 2019 standard. Therefore, the homemade lung phantom is feasible for clinical quality control of Cyberknife.

The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.

BACKGROUND:The study of the lumbar spine and pelvis in patients with Lenke type 5 lordosis is limited to the coronal and sagittal planes,and the three-dimensional relationship between the scoliosis and the pelvis has not yet been clarified. OBJECTIVE:To analyze the effect of lumbar scoliosis on the pelvis in patients with Lenke type 5 lordosis and to study the correlation between the lumbar spine and the three-dimensional spatial position of the pelvis. METHODS:Imaging data of 60 patients with Lenke type 5 lordosis scoliosis admitted to the 3D Printing Reception Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2019 to September 2023 were retrospectively analyzed,including Cobb angle,coronal pelvic tilt,lumbar lordosis,left and right pelvic hip width ratio(sacroiliac-anterior superior iliac spine),spinal rotation angle,pelvic tilt,sacral slope,pelvic incidence,coronal deformity angular ratio,sagittal deformity angular ratio,C7 plumb line-center sacral vertical line,apical vertebral translation,and coronal sacral inclination.The information was summarized as a database.SPSS 22.0 software was used to analyze the data related to the lumbar spine and pelvis of the patients with Lenke type 5 primary lumbar curvature adolescent idiopathic scoliosis using Spearman's correlation analysis and linear regression. RESULTS AND CONCLUSION:(1)Cobb angle was highly positively correlated with coronal deformity angular ratio,apical vertebral translation,and spinal rotation angle(r=0.91,r=0.841,r=0.736).(2)Coronal deformity angular ratio was highly positively correlated with apical vertebral translation(r=0.737),moderately positively correlated with C7 plumb line-center sacral vertical line(r=0.514),and moderately negatively correlated with sagittal deformity angular ratio(r=-0.595).(3)There was a high positive correlation between lumbar lordosis and sagittal deformity angular ratio(r=0.942)and a moderate negative correlation with coronal deformity angular ratio(r=-0.554).(4)There was a moderate positive correlation between Cobb angle with coronal pelvic tilt and coronal sacral inclination(r=0.522,r=0.534)and a moderate positive correlation between C7 plumb line-center sacral vertical line and coronal pelvic tilt(r=0.507).Apical vertebral translation with coronal pelvic tilt and coronal sacral inclination showed a moderate positive correlation(r=0.507,r=0.506).Lumbar lordosis with sacral slope and pelvic incidence showed a moderate positive correlation(r=0.512,r=0.538).Sagittal deformity angular ratio was moderately positively correlated with sacral slope and pelvic incidence(r=0.614,r=0.621).(5)Studies have found that the relative position of the lumbar spine and the pelvis is closely related in the horizontal,sagittal and coronal planes.When the lumbar spine affects scoliosis and is rotated,the relative position of the pelvis will also change to compensate,which indicates that while correcting scoliosis,the correction of the pelvis cannot be ignored.

OBJECTIVE To evaluate the accuracy of three individualized drug delivery tools， i.e. JPKD， SmartDose and NextDose， in predicting tacrolimus dose and blood concentration after kidney transplantation， and analyze the influential factors of prediction accuracy. METHODS The clinical data of adult hospitalized patients treated with tacrolimus after kidney transplantation from January 2021 to June 2023 were retrospectively collected. Three individualized dosing tools， i.e. JPKD， SmartDose and NextDose， were used to predict the dose and plasma concentration of tacrolimus. The absolute prediction error （APE） and prediction error （PE） between the measured value and the predicted value， and prediction success rate were calculated （APE＜30% indicating a good forecast）. Pearson assay or Spearman assay was used to analyze the correlation between the predicted dosage and actual dosage， as well as the predicted and measured blood concentration values using three software； univariate analysis was used to investigate the influential factors for prediction accuracy of JPKD， SmartDose and NextDose. RESULTS A total of 110 hospitalized patients were included in this study， and tacrolimus doses and plasma concentrations were monitored. The predicted doses of JPKD， SmartDose and NextDose were （2.0±0.7）， （2.7±1.9）， （1.8±0.8） mg， their measured value was （1.9±0.6） mg， and the correlation coefficients between the predicted values and the measured value were 0.841， 0.450， 0.247 （P＜0.001）； the median APEs were 6.00%， 52.07% and 30.40%， and the median PEs were 5.00%， 18.50% and －3.50%； the prediction success rates were 98.45%， 30.05% and 49.22%. The predicted values of tacrolimus concentrations using JPKD， SmartDose， NextDose were （6.74±3.36）， （6.93±5.02）， 9.00（5.80±12.60） ng/mL， the measured value was 8.64（7.11，9.77） ng/mL， and the correlation coefficients between the predicted values and the measured value were 0.997 （P＜0.001）， －0.066 （P＝0.360）， 0.920 （P＜0.001）. The median APEs were 5.54%， 45.91% and 35.56%， and PEs were －4.94% （median）， －17.050% （median） and 36.93% （average value）； the prediction success rates were 97.93%， 32.64% and 37.31%. Univariate analysis showed that the dosage， blood concentration， body weight， transplantation time and others were related to the prediction accuracy （P＜0.05）. CONCLUSIONS The good prediction rates of tacrolimus dose and blood concentration in kidney transplant patients using three personalized drug delivery tools， from high to low， are JPKD， NextDose， and SmartDose， suggesting that JPKD can be prioritized in clinical use.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

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 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.