Twelve compounds were isolated from the rice fermentation extracts of Penicillium expansum GY618 by silica column chromatography, Sephadex gel column chromatography, ODS column chromatography and semi preparative HPLC methods. They were determined as 11-hydroxyl-penicitrinone F (1), penicitrinone F (2), betulin (3), erythrodiol (4), ergosterol (5), ergost-5α,8α-epidioxy-6,22-dien-3β-ol (6), (5α,8α-epidioxy-(22E,24R)-ergosta-6,9(11),22-trien-3β-ol) (7), 5α,8α-epidioxy-(22E,24R)-23-methylergosta-6,22-dien-3β-ol (8), 5α,8α-epidioxy- 23,24(R)-dimethylcholesta-6,9(11),22-trien-3β-ol (9), dankasterone A (10), (17R)-4-hydroxy-17-methylincisterol (11) and ergosta-4,6,8(14),22-tetraen-3-one (12), through mass spectrometer, nuclear magnetic resonance (NMR) and comparison with the literature. Compound 1 was a new compound and compounds 2-4, 6-12 were isolated from Penicillium expansum fungus for the first time. The tyrosinase inhibitory activity experiment showed that compounds 1, 3 and 12 showed certain inhibitory activity against tyrosinase with IC₅₀ values of (75 ± 9), (69 ± 8) and (64 ± 2) μmol·L^-1, respectively. The IC₅₀ of other compounds were all greater than 100 μmol·L^-1, while IC₅₀ of the positive control kojic acid was (46 ± 4) μmol·L^-1.

ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.

Objective To observe the effect of different concentrations of glutamine(Gln)on the radiosensitivity of colorectal cancer HT-29 cells and explore the possible mechanism.Methods According to different Gln concentrations,HT-29 cells at logarithmical growth were divided into control group(2 mmol/L,as the basal medium concentration group)and experimental groups Ⅰ,Ⅱ and Ⅲ(4,6 and 8 mmol/L).After a 2-hour pre-treatment,all groups were exposed to 8 Gy irradiation of a Co-60 radiation source.CCK-8 assay and clonal formation assay were used respectively to explore the effects of different Gln concentrations on cell viability and cell radiosensitivity after irradiation.The level of reactive oxygen species(ROS)in each group was measured in 24 h after irradiation,and the apoptotic rate was detected with flow cytometry in 48 h after irradiation.The protein expression levels of Nrf2,HO-1,and cleaved-Caspase3 were determined by Western blotting.Results In 24 h after Gln intervention,the cell viability of experimental groups Ⅱ and Ⅲof non-irradiated HT-29 cells was significantly higher than that of the control group and of experimental group Ⅰ(P＜0.05).In 24 h after radiation,the cell viability of each experimental group was significantly higher than that of the control group(P＜0.05).In 14 d after radiation,there were more clone formation in each experimental group than the control group(P＜0.05).The ROS level was significantly lower in each experimental group than the control group in 24 h after radiation(P＜0.05).After 48 h of radiation,the apoptotic rate was notably lower in each experimental group than the control group(P＜0.05).The expression level of Nrf2 in the experimental group Ⅰ was higher than that of the control group(P＜0.05),those of Nrf2 and HO-1 in the experimental groups Ⅱ and Ⅲ were higher than those of the control group and experimental group Ⅰ(P＜0.05).While the expression of cleaved-Caspase3 in the experimental groups Ⅱ and Ⅲ was lower than the control group and experimental group Ⅰ(P＜0.05),and it in the experimental group Ⅲ was lower than that of experimental group Ⅱ(P＜0.05).Conclusion Gln can significantly reduce the radiosensitivity of HT-29 cells,which is associated with its reducing oxidative stress damage and reducing cell apoptosis.Our results suggest that Gln might be detrimental to radiation therapy in patients with colorectal cancer.

Objective:In thyroid surgery,evaluating the combination of near-infrared auto-fluorescence imaging(NIRAF)with injection of mitoxantrone hydrochloride(MHI)as a tracer to en-hance the identification rate of parathyroid glands,thereby reducing the occurrence of post-thyroidectomy hypocalcemia and parathyroid dysfunction.Methods:A prospective study was conducted from October 2022 to March 2023 at Yidu Central Hospital in Weifang City,involving 80 patients undergoing thyroid surgery.Patients were randomly divided into a combined group and a control group based on their admission time,with 40 patients in each group.In the combined group,0.6 mL of mitoxantrone hydrochloride(MHI)was injected into the thyroid gland during sur-gery,and near-infrared autofluorescence(NIRAF)was used for parathyroid gland identification.The control group only used NIRAF during surgery.Compared the preoperative levels of serum calcium and parathyroid hormone(PTH)between the two groups,as well as the intraoperative accuracy of parathyroid gland identification and the rate of autotransplantation.Postoperatively,the study ana-lyzed PTH levels,blood calcium levels,the rate of inadvertent parathyroidectomy,and the inci-dence of hypocalcemia symptoms.Results:In the combined group,there were 4 cases(10.0％)of parathyroid transplantation,compared to 12 cases(30.0％)in the control group,with a statisti-cally significant difference between the two groups(x2=3.828,P=0.049).The accuracy of parathy-roid gland identification in the combined group was higher than that in the control group(x2=3.899,P=0.048).Additionally,there were 2 cases(5.0％)of inadvertent parathyroidectomy in the com-bined group compared to 10 cases(25.0％)in the control group,with a statistically significant dif-ference between the two groups(x2=4.804,P=0.028).Postoperatively at day 1,the blood calcium levels were(2.24±0.11)mmol/L in the combined group and(2.16±0.17)mmol/L in the control group,and the PTH levels were(27.18±11.77)ng/L in the combined group and(18.57±9.55)ng/L in the control group,with statistically significant differences(P＜0.05)observed in both parameters.At day 3 postoperatively,the blood calcium levels were(2.32±0.17)mmol/L in the combined group and(2.23±0.12)mmol/L in the control group;the PTH levels were(33.03±7.88)ng/L in the com-bined group and(24.89±9.29)ng/L in the control group,with statistically significant differences(P＜0.05)observed in both parameters.After surgery,3 cases(7.5％)of numbness in the extremities or around the mouth were observed in the combined group compared to 10 cases(25.0％)in the con-trol group,with a statistically significant difference(P=0.034).Conclusion:The use of NIRAF combined with MHI can effectively improve the accuracy of parathyroid gland identification during thyroid surgery,thereby avoiding inadvertent removal,reducing the occurrence of postoperative hypocalcemia and parathyroid dysfunction,lowering the incidence of postoperative numbness in the extremities or around the mouth,and enhancing the overall patient experience.

Objective:To investigate the relationship and clinical significance of circulating tu-mor DNA(ctDNA)methylation with postoperative recurrence of thyroid cancer.Method:5 pa-tients with recurrent thyroid cancer in our hospital from March 2021 to April 2022 were selected as the observation group,and 2 healthy volunteers were selected as the control group.The level of ctDNA methylation in peripheral blood of the two groups was detected by Illumina high-throughput sequencing system.Gene ontology(GO)function analysis and Kyoto gene and genome encyclope-dia(KEGG)signal pathway analysis were carried out on the methylation region genes with signifi-cant differences through the DAVID gene function analysis platform.Result:There were 7787 dif-ferential ctDNA methylation sites between the two groups.2914(37.4％)were hypermethylation sites and 4873(62.6％)were low methylation sites.GO functional analysis showed that differentially methylated genes were enriched in molecular functions such as DNA-binding transcriptional acti-vation,cell-substrate adhesion,glycoprotein complex and other cellular components.KEGG path-way analysis showed that differentially methylated genes were enriched in thyroid carcinoma signal pathway,cell adhesion molecules,RAP1 signal pathway,RAS signal pathway,MAPK signal path-way and so on.Conclusion:ctDNA methylation may be involved in cancer recurrence in postop-erative patients with thyroid cancer.Monitoring the level of ctDNA methylation in peripheral blood may be an effective method to indicate the recurrence or metastasis of thyroid cancer and guide clinical diagnosis and treatment.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

OBJECTIVE: To explore the effect of a modified three-point bending fracture device for establishing a rabbit model of closed tibial fracture. METHODS: The model of closed tibial fracture was established in 40 6-month-old male New Zealand white rabbits with a body weight of 2.5 to 3.0 kg, and the model was verified at 6 weeks after operation. Five rabbits underwent pre modeling without temporary external fixation before modeling, and then were fractured with a modified three-point bending fracture device;35 rabbits underwent formal modeling. Before modeling, needles were inserted, and splints were fixed externally, and then the fracture was performed with a modified three-point bending fracture device. The fracture model and healing process were evaluated by imaging and histopathology at 2 hours, 4 weeks, and 6 weeks after operation. RESULTS: Two hours after modeling, the prefabricated module showed oblique fracture in varying degrees and the broken end shifted significantly;Except for 1 comminuted fracture, 2 curved butterfly fractures and 2 without obvious fracture line, the rest were simple transverse and oblique fractures without obvious displacement in formal modeling group. According to the judgment criteria, the success rate of the model was 85.71%. Four weeks after modeling, the fixed needle and splint of the experimental rabbits were in good position, the fracture alignment was good, the fracture line was blurred, many continuous callus growths could be seen around the fracture end, and the callus density was high. Six weeks after modeling, many thick new bone trabeculae at the fracture, marginal osteoblasts attached, and a small number of macrophages were seen under the microscope. The intramembrane osteogenesis area was in the preparation bone stage, the medullary cavity at the fracture had been partially reopened, the callus was in the absorption plastic stage, and many osteoclasts were visible. The X-ray showed that the fracture line almost disappeared, part of the medullary cavity had been opened, the external callus was reduced around, the callus was in the plastic stage, and the bone cortex was continuous. It suggests that the fracture model showed secondary healing. CONCLUSION The improved three-point bending fracture device can establish a stable rabbit model of closed tibial fracture, and the operation is simple, which meets the requirements of closed fracture model in basic research related to fracture healing.
Rabbits ; Male ; Animals ; Bony Callus ; Fracture Healing ; Tibial Fractures/surgery* ; Osteogenesis ; Radiography

OBJECTIVES: To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children. METHODS: A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed. RESULTS: Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered. CONCLUSIONS Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.
Child ; Humans ; Retrospective Studies ; Syndrome ; Kidney Diseases, Cystic/genetics* ; Mutation ; Phenotype