Based on the epidermal growth factor receptor(EGFR)/mitogen-activated protein kinase(MAPK) signaling pathway-mediated cell proliferation, this study explores the effect of cisplatin combined with Guiqi Yiyuan Ointment on Lewis lung cancer-bearing mice. A total of 60 male C57BL/6 mice were randomly divided into a blank group with 10 mice and a modeling group with 50 mice. After modeling, they were randomly divided into the model group, cisplatin group, and low-, medium-, and high-dose groups of cisplatin combined with Guiqi Yiyuan Ointment, with 10 mice in each group. After 14 days of medication, the general condition of the mice was observed; body weight was measured, and organ index and tumor inhibition rate were calculated. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology changes in tumor tissue. Immunohistochemistry was used to detect the positive rate of Ki-67 antigen(Ki-67) and proliferating cell nuclear antigen(PCNA) in tumor tissue. Western blot and real time-quantitative polymerase chain reaction(qPCR) were used to detect the expression of related proteins and mRNA in tumor tissue. Flow cytometry was used to detect the cell cycle of tumor cells in tumor tissue. The results showed that compared with that in the blank group, the general condition of mice in the model group deteriorated; the body weight, as well as thymus and spleen index of mice in the model group decreased after 14 days of medication. Compared with that in the model group, the general condition of mice in the cisplatin group deteriorated, while the condition of mice in the combined groups improved; the body weight, as well as thymus and spleen index of mice in the cisplatin group decreased, while the three indicators in the combined groups increased; the tumor weight of each medication group decreased, and the tumor inhibition rate increased; there were varying degrees of necrosis in tumor cells of each medication group, and the tightness of tumor cells, the increase in the number of cell nuclei and chromatin, and mitosis all decreased. The positive rate of Ki-67 and PCNA, as well as the protein expression and ratio of p-EGFR/EGFR, rat sarcoma viral oncogene homolog(Ras), phosphorylated Raf-1 protein kinase(p-Raf-1)/Raf-1, phosphorylated mitogen-activated protein kinase kinase(p-MEK)/MEK, phosphorylated extracellular signal-regulated kinase(p-ERK)/ERK and the mRNA expression of EGFR, Ras, Raf-1, MEK, and ERK all decreased. The proportion of tumor cells in the G_0/G_1 phase of each medication group increased, and that in the S phase decreased. In addition, there was no significant difference in the G_2/M phase. Compared with that of the cisplatin group, the tumor weight of the combined groups decreased, and the tumor inhibition rate increased. The necrosis and mitosis of tumor cells in the combined groups were more pronounced; the positive rate of Ki-67 and PCNA, the protein expression and ratio of p-EGFR/EGFR, Ras, p-Raf-1/Raf-1, p-MEK/MEK, and p-ERK/ERK, as well as the mRNA expression of EGFR, Ras, Raf-1, MEK, and ERK in the combined groups all decreased. The proportion of tumor cells in the G_0/G_1 phase of the combined medium-and high-dose groups increased, and that in the S phase decreased. There was no significant difference in the proportion of tumor cells of the combined groups in the G_2/M phase. This indicates that the combination of cisplatin and Guiqi Yiyuan Ointment can enhance the anti-tumor effect of cisplatin on tumor-bearing mice, and the mechanism may be associated with the inhibition of the EGFR/MAPK pathway, which accelerates the arrest of tumor cells in the G_0/G_1 phase, thereby inhibiting the proliferation of tumor cells. At the same time, the study also indicates that Guiqi Yiyuan Ointment may reduce the damage of tumors to mice and the toxic side effects brought by cisplatin chemotherapy.
Animals ; Male ; Carcinoma, Lewis Lung/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; ErbB Receptors/genetics* ; Mice ; Cisplatin/administration & dosage* ; Mice, Inbred C57BL ; Cell Proliferation/drug effects* ; Ointments/administration & dosage* ; MAP Kinase Signaling System/drug effects* ; Humans ; Antineoplastic Agents/administration & dosage* ; Lung Neoplasms/metabolism*

Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.

Objective To investigate the feasibility of simultaneous multi-slice(SMS)acquisition combined with single-shot echo-planar imaging(SSEPI)multi-model diffusion weighted imaging(DWI)for breast lesions.Methods Totally 108 cases of breast lesions were retrospectively enrolled and divided into malignant group(n=66)and benign group(n=42)based on pathology.3.0T MR scanner was used to acquire SSEPI and SMS-SSEPI multi-b values DWI,7 derived parameters were obtained through post-processing with mono-exponential,fractional-order calculus(FROC)and continuous-time random walk(CTRW)models.Then the imaging quality and derived parameters of SMS-SSEPI and SSEPI DWI were compared between groups.Spearman correlation analysis was performed to explore the relationships of corresponding parameters between SMS-SSEPI DWI and SSEPI DWI.Diagnostic performance of each parameter for distinguishing malignant and benign lesions was evaluated according to the area under the receiver operating characteristic curve(AUC).Results Background noise score of SMS-SSEPI DWI was lower than that of SSEPI DWI(P＜0.05),whereas no significant difference of overall imaging quality,normal anatomical structure depiction,lesion conspicuity,geometric distortion,signal-to-noise ratio(SNR)nor contrast-to-noise ratio(CNR)was found between SMS-SSEPI DWI and SSEPI DWI(all P＞0.05).Parameters derived from SMS-SSEPI DWI were all moderately to highly positively correlated with those from SSEPI DWI(rs=0.66-0.98).Malignant lesions exhibited significantly lower apparent diffusion coefficient(ADC),diffusion coefficient based on FROC(DFROC),fractional order derivative in space(βFROC),diffusion coefficient based on CTRW(DCTRW),temporal diffusion heterogeneity index(αCTRW)and spatial diffusion heterogeneity index(βCTRW)values,but higher spatial parameter(μFROC)value than benign lesions(all P＜0.05).AUC of SMS-SSEPI DWI derived parameters for differentiating malignant from benign lesions were 0.699-0.900,of those from SSEPI DWI were 0.654-0.887,while in both SMS-SSEPI DWI and SSEPI DWI,DFROC had the highest diagnostic efficacy(AUC=0.900,0.887).Conclusion SMS-SSEPI DWI could be used to effectively differentiate malignant and benign breast lesions.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective To investigate the value of fractional-order calculus(FROC)and continuous-time random-walk(CTRW)diffusion models based on readout segmentation of long variable echo-trains(RESOLVE)in identifying benign and malignant lesions in the head and neck.Methods A retrospective analysis was conducted on 61 patients pathologically confirmed head and neck lesions,including 19 benign lesions(BL)and 42 malignant lesions(ML).The ML were further divided into a lymphoma subgroup(LS)with 9 cases(14 lesions)and a non-lymphoma malignant lesion subgroup(MLS)with 33 cases.The parameters of DFROC,βFROC,μFROC,DCTRW,αCTRW and βCTRW were obtained from the two diffusion models;Independent sample t-tests or U tests were used to compare the differences in each parameter between benign and malignant groups and among various subgroups,and the receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of each parameter.Area under the curve(AUC)was compared by DeLong test.Results DFROC,μFROC,DCTRW and αCTRW showed significant differences between benign and malignant,BL and LS,BL and MLS and LS and MLS,with αCTRW showed the highest diagnostic efficacy;βFROC showed differences between BL and LS,BL and MLS,whileβCTRW did not show differences between benign and malignant groups,and among subgroups.Conclusion FROC and CTRW diffusion models based on RESOLVE can distinguish between benign and malignant head and neck lesions with multiple parameters,and provide metrics reflecting tissue heterogeneity.

Objective To compare the effect of different intensity of neuromuscular training(NMT)on muscle strength and knee joint function of patients after anterior cruciate ligament reconstruction(ACLR).Methods From January,2023 to January,2024,60 ACLR patients in Changhai Hospital were selected,and they received the same intensity of NMT from one to eight weeks after surgery.Eight weeks after surgery,they were randomly divided into low intensity group(n=30)and high intensity group(n=30),and then they received different inten-sities of NMT from nine to 16 weeks after surgery,each training session lasted one hour,with three sessions per week,totaly 48 sessions.The Lysholm score,knee flexor and extensor muscle strength and muscle endurance-were compared at eight weeks and 16 weeks after surgery.Results After group training,the Lysholm score significantly increased in both groups(|t|>13.739,P<0.001),and was higher in the high intensity group than in the low intensity group(t=-2.574,P<0.05);in the high intensity group,the relative peak torque and endurance of the extensor and flexor muscles improved at angular velocities of 60°/s,120°/s and 180 °/s(|t|>2.320,P<0.05);in the low intensity group,the flexor peak torque improved at all the three angular velocities(t>2.177,P<0.05),the extensor peak torque improved at angular velocities of 60°/s and 180°/s(|t|>1.715,P<0.05),and the extensor endurance improved at angular velocity of 60°/s(t=-2.293,P<0.05).However,there was no significant difference in the relative peak torque and endurance of the extensor and flexor muscles at all the three angular velocities(P>0.05).Conclusion Both high and low intensity NMT could improve the muscle strength,muscle endurance and knee joint func-tion.Maybe,high intensity is superior to low intensity.Further verification is still needed.

Objective To observe the value of conventional MRI and diffusion weighted imaging(DWI)for differentiating soft tissue lymphoma(STL)and soft tissue sarcoma(STS).Methods Conventional MRI and DWI data of 25 cases of STL(STL group)and 38 cases of STS(STS group)were retrospectively analyzed.MRI features being statistically different between groups were included in logistic regression analysis to screen the independent risk factors of STL and to evaluate the sensitivity,specificity and accuracy of their combination for predicting STL.Receiver operating characteristic curve was generated,the area under the curve(AUC)was calculated to assess the diagnostic efficacy of the mean apparent diffusion coefficient(ADCmean),the minimum apparent diffusion coefficient(ADCmin),the maximum apparent diffusion coefficient(ADCmax)values for distinguishing STL from STS.Results Slightly hyperintensity on T1WI,non-necrosis,involvement of multiple muscle groups and homogeneous enhancement were all independent risk factors of STL(all P＜0.05).The sensitivity,specificity and accuracy of their combination for predicting STL was 72.00％(18/25),89.47％(34/38)and 82.54％(52/63),respectively.ADCmean,ADCmin and ADCmax values of STL was(1.06±0.18)× 10-3,(0.77±0.14)×10-3 and(1.47±0.31)× 10-3mm2/s,respectively,all lower than those of STS([1.31±0.17]× 10-3,[1.02±0.23]× 10-3 and[1.64±0.16]× 10-3 mm2/s;t=-4.829--2.498,all P＜0.05).The AUC of ADCmean,ADCmin and ADCmax values and their combination for differential diagnosis of STL and STS was 0.845,0.844,0.683 and 0.877,respectively.Conclusion Conventional MRI features,including T1WI signal intensity,necrosis,involvement of multiple muscle groups and enhancement pattern,along with ADCmean and ADCmin values derived from DWI contributed to differentiating STL and STS.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

OBJECTIVES: To study the clinical and genetic characteristics of children with congenital adrenal hyperplasia (CAH). METHODS: Clinical data, laboratory findings, and genetic test results of 63 children diagnosed with CAH at Henan Children's Hospital from January 2017 to December 2024 were retrospectively reviewed. RESULTS: Of the 63 patients, the mean age at the first visit was (21 ± 14) days; 29 (46%) were of male sex and 34 (54%) were of female sex. The predominant clinical manifestations were poor weight gain or weight loss (92%, 58/63), poor feeding (84%, 53/63), skin hyperpigmentation (83%, 52/63), and female external genital anomalies (100%, 34/34). Laboratory abnormalities included hyponatremia (87%, 55/63), hyperkalemia (68%, 43/63), metabolic acidosis (68%, 43/63), and markedly elevated 17-hydroxyprogesterone (92%, 58/63), testosterone (89%, 56/63), and adrenocorticotropic hormone (81%, 51/63). Among 49 patients who underwent genetic testing, CYP21A2 variants were identified in 90% (44/49), with c.293-13A/C>G (33%, 30/91) and large deletions/gene conversions (29%, 26/91) being the most frequent; STAR (8%, 4/49) and HSD3B2 (2%, 1/49) variants were also detected. Following hormone replacement therapy, electrolyte disturbances were corrected in 57 cases, with significant reductions in 17-hydroxyprogesterone, adrenocorticotropic hormone, and testosterone levels (P<0.001). CONCLUSIONS CAH presenting in neonates or young infants is characterized by electrolyte imbalance, external genital anomalies, and abnormal hormone levels. Genetic testing enables definitive subtype classification; in CYP21A2-related CAH, c.293-13A/C>G is a hotspot variant. These findings underscore the clinical value of genetic testing for early diagnosis and genetic counseling in CAH. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(11): 1367-1372.
Humans ; Adrenal Hyperplasia, Congenital/diagnosis* ; Male ; Female ; Retrospective Studies ; Infant ; Infant, Newborn