ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

ObjectiveTo observe the apoptosis induced by paeoniflorin （PF） in non-small cell lung cancer （NSCLC） cells and explore its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the inhibition rates of H1299， H292 and A549 cells with different concentrations of PF （2.5， 5， 10， 20， 25 µmol·L^-1）， and to screen suitable concentrations of PF and experimental cells. The inhibitory effect of PF on lung cancer cells was detected by clone formation assay. The effect of PF on cell apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide （PI） double staining. With the right concentration of drugs， levels of apoptosis-associated protein B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3 and Caspase-3 were detected by Western blot. At the same time， the molecular expressions of hypoxia inducible factor -1α （HIF-1α） and Hippo signaling pathway were determined. ResultCompared with the blank group， PF significantly inhibited the growth of H1299， H292 and A549 cells of human lung cancer （P<0.01）. PF significantly induced apoptosis in A549 cells （P<0.01）， decreased the Bcl-2/Bax ratio （P<0.01）， and significantly increased the cleaved Caspase-3 expression （P<0.01）. Compared with those in the blank group， the expression levels of HIF-1α， transcriptional coactivator with PDZ-binding motif （TAZ）， large tumor suppressor 1 （LATS1）， Mps one binding 1 （MOB1） and Yes-associated protein （YAP） in A549 cells of the PF treatment group were significantly decreased （P<0.01）， while the expressions of p-LATS1， p-MOB1 and p-YAP were significantly increased （P<0.01）. At the same time， there was no significant effect on the expression levels of phosphorylated mammalian Ste20-like kinase 1 （p-MST1） and MST1， which did not reach a statistical difference. ConclusionAll data demonstrated that PF showed an anti-tumor effect by improving hypoxic conditions and inhibiting the abnormally activated Hippo signaling pathway， thereby inducing and promoting apoptosis in non-small cell lung cancer.

Objective:To investigate the clinical efficacy of 3D printed metal augment or tibial prosthesis for reconstruction of large bone defects in total knee arthroplasty (TKA) and knee revision surgery.Methods:A total of 7 patients (7 knees) with TKA or knee revision who were admitted to the Department of Orthopaedics of the Second Affiliated Hospital of Zhejiang University School of Medicine with large bone defects from July 2018 to December 2023 were retrospectively analyzed, including 4 patients with TKA and 3 patients with knee revision. There were 3 males and 4 females, aged 58.7±7.6 years (range, 54-68 years), 3 patients with left knee and 4 patients with right knee. All the patients had bone defects in the knee joint (AORI type III), 2 cases had bone defects only in the femur, 4 cases had bone defects only in the tibia, and 1 case had bone defects in both the tibia and femur, which were treated with personalized reconstruction using 3D printing. Hip-knee-ankle angles, American Knee Society score (KSS) before and after surgery were compared, and postoperative complications were observed.Results:All patients successfully completed the operation, and the operation time was 189.3±35.5 min (range, 125-240 min). Complex TKA was performed in 4 cases with surgical times of 175, 195, 210, and 240 min, and revision surgery was performed in 3 cases with surgical times of 125, 180, and 200 min, respectively. Intraoperative blood loss was 114±24.4 ml (range, 100-150 ml). Five cases used 3D printed metal augment, and two used 3D printed one-piece tibial components. All patients were followed up for 2, 2, 5, 6, 7, 20, 57 months, respectively. The KSS of the five patients at 3 months postoperatively were 56, 61, 66, 56, and 56 points, respectively, greater than the preoperative scores of 35, 44, 36, 27, and 41 points. The KSS functional scores of the five patients at 3 months postoperatively were 45, 45, 45, 30, and 45 points, respectively, which were greater than the preoperative scores of 30, 30, 15, 20, and 20 points. The hip-knee-ankle angle was 181.8°±3.4° (range, 177.9° to 188.0°) at the final follow-up and 175.8°±12.4° (range, 153.3° to 192.1°) before surgery, with no significant difference ( t=-1.230, P=0.242). At the final follow-up, the 3D printed component was well integrated with the bone surface, the prosthesis was securely positioned, and the force lines of the lower limbs were normal. There were no postoperative complications such as poor wound healing, infection, fat liquefaction, nerve injury, deep vein thrombosis of lower limbs, knee joint stiffness, periprosthesis infection and loosening. Conclusion:Using 3D printed metal augment or tibial prosthesis to reconstruct the huge bone defect in TKA and revision has a satisfactory early clinical effect, satisfactory joint function and good surgical safety.

Objective:To investigate the status quo and influencing factors of social isolation of parents of children with autism spectrum disorder in order to provide theoretical basis for clinical intervention measures.Methods:A total of 340 parents of children with autism spectrum disorder who visited the Children′s Developmental Behavior Center of Third Affiliated Hospital of Sun Yat sen University were selected by the convenience sampling method as research objects during July to November 2023. A cross-sectional survey was investigated by a general information questionnaire, General Alienation Scale, Social Avoidance and Distress Scale, Affiliate Stigma Scale, Family APGAR Index, Chinese Simplified Version of Social Support Scale, and Social Responsiveness Scale.Results:A total of 323 valid questionnaires were collected, including 235 mothers and 88 fathers; 33 individuals aged 25-29 years, 233 individuals aged 30-39 years, and 57 individuals aged 40-60 years. The subjective social isolation score of parents of children with autism spectrum disorder was 33.24 ± 4.92 and the objective social isolation score was 4.00(2.00,7.00). The results of multiple linear regression analysis showed that the subjective social isolation of parents of children with autism spectrum disorder was influenced by factors including self-assessed health status, whether they worked full-time or not, whether they were satisfied with the division of labor in the family caring for their children, affiliate stigma, family care, and social support (all P<0.05); and the objective social isolation of parents was influenced by factors including the severity of autism symptoms, self-assessed health status, affiliate stigma, and family care (all p<0.05). Conclusions:Parents of children with autism spectrum disorder had some degree of social isolation, and the level of subjective social isolation was higher than objective social isolation. Healthcare professionals should pay attention to parents of autistic children who have high levels of symptom severity, poor self-rated health, do not work full-time, and are dissatisfied with the division of labor in the family caring for their child, and take measures to reduce the affiliate stigma, and to increase the level of family care and social support, so as to improve the social isolation of parents of children with autism spectrum disorder.

Purpose To investigate the clinicopathological features and molecular features of diffuse paediatric-type high-grade glioma,H3-wildtype and IDH-wildtype(pHGG H3/IDH WT)of central nervous system.Methods The clinical and pathological data of 6 cases of pHGG H3/IDH WT diagnosed by Department of Pathology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine were retrospectively ana-lyzed.The expression of GFAP,Olig2,Syn,NeuN,IDH1,H3K27M was detected by immunohistochemistry(automatic im-munohistochemical staining device).The EGFR and MYCN gene amplification was detected by FISH.IDH,H3F3A and TERT gene mutations were detected by Sanger sequencing.The literatures were reviewed.Results The 6 patient's age ranged from 5 to 11 years,with a median age of 7.5 years.Among them,there were 2 males and 4 females,with a male to female ratio of 1∶2.The clinical symptoms were limb weakness,hemi-plegia,vomiting,convulsions,blurred vision and so on.Tumors were located in supratentorial brain for 5 cases and one in brain stem and cerebellum.Histologically,3 cases showed the mor-phological features of high-grade glioma,2 of which with giant cells.Two cases showed embryonal tumor-like features,and one had both high-grade glioma and embryonal tumor-like morpho-logical features.Microvascular proliferation and/or necrosis were present in 5 cases.Myxoid/microcystic stroma was found in 1 case.By immunohistochemistrically,the tumor cells were par-tially or focally positive for GFAP(6/6)and Olig2(6/6),fo-cally positive for Syn(3/6)and NeuN(1/6),and negative for IDH1,H3K27M,H3G34V and H3G34R.ATRX,H3K27me3,INI1 and BRG1 were diffusely positive(6/6).The positive rate of p53 was 5％-95％,and Ki67 proliferation index was 40％-90％.Molecular analysis showed that all 6 cases were IDH1/2 and H3F3A wild-type.MYCN amplification was observed in 2 cases.Two cases of EGFR amplification with polyploidy;one case had both EGFR amplification and MYCN amplification.PDGFRA amplification was observed in one case.For treatment and follow-up,the patients received postoperative radiotherapy and/or temozolomide chemotherapy;three patients died at 1 to 5 months after operation.Two patients survived and were followed up for 4 and 7 months,respectively.One patient was lost to fol-low-up.Conclusions pHGG H3/IDH WT is a highly malignant tumor with glioblastoma-like or embryonal tumor-like features.According to the molecular characteristics,it can be divided into three molecular subtypes,RTK1,RTK2 and MYCN.pHGG MYCN has the worst prognosis.Attention should be paid to the differential diagnosis of other pediatric or adult high-grade glio-mas and embryonal tumors.

Purpose To investigate the clinicopathological features,molecular features,treatment and prognosis of infant-type hemispheric glioma(IHG)with ALK gene fusion of central nervous system.Methods Clinical data of 2 cases of IHG were collected,and the expression of GFAP,Olig2,Syn,NeuN,H3K27M,H3K27me3,H3G34V,H3G34R,ALK,and BRAF were detected using immunohistochemistry.FISH and NGS method was used to detect ALK fusion genes,and relevant liter-atures were reviewed.Results Case 1,a male,15 months old,showed a huge mass in the left frontal and temporal lobe on cranial MRI.Case 2(external hospital consultation),a male,18 months old,was found to have a space occupying lesion in the frontaltemporal lobe.Microscopic examination:in case 1,tumor cells showed diffuse patchy pattern,with small nodular shapes in some areas which separated by fibrous blood vessels.The cell density was high,and the nucleus was round or oval.The mitotic was easy to see,accompanied by bleeding and nec-rosis.In case 2,tumor cells were diffusely distributed,some of them formed pseudorosette around blood vessels and others ar-ranged in bundles.The cells were mild to moderate dysplasia with round or oval nuclei,light staining,small nucleoli,rare mitotic figures,and no microvascular proliferation or necrosis.Immunophenotypes:in case 1 tumor cells were focal positive for GFAP and NeuN,diffuse positive for H3K27me3,ALK(cyto-plasm and cell membrane),and ATRX,p53 positive(30％),negative for Olig2,Syn,H3K27M,H3G34V,H3G34R,and BRAF,Ki67 proliferation index of 20％.In case 2:tumor cells were diffusedly expressed GFAP,ATRX,H3K27me3,ALK(cytoplasm and cell membrane),and Olig2,Syn was weakly positive,NeuN and p53 were negative,and Ki67 proliferation index was 5％.FISH and NGS tests showed ALK gene fusion in both cases,with EML4::ALK fusion in case 1 and LRRFIP1::ALK fusion in case 2.Follow up for 7 months showed that the residual lesion in case 1 had shrunk and was generally in good condition;case 2 lost follow-up.Conclusion The histology of IHG often presents as high-grade gliomas or accompanied by an-aplastic features.The heterogeneity of ALK variants can also manifest as low-grade gliomas,which need to be differentiated from other high-grade gliomas,desmoplastic infantile gangliogli-oma/astrocytoma,ependymoma,etc.

Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.
Female ; Humans ; Proto-Oncogene Proteins c-akt ; Phosphatidylinositol 3-Kinases ; Endometrial Neoplasms ; Estrogens ; Breast Neoplasms ; DNA Helicases

BACKGROUND: In recent years, immunotherapy represented by programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunosuppressants has greatly changed the status of non-small cell lung cancer (NSCLC) treatment. PD-L1 has become an important biomarker for screening NSCLC immunotherapy beneficiaries, but how to easily and accurately detect whether PD-L1 is expressed in NSCLC patients is a difficult problem for clinicians. The aim of this study was to construct a Nomogram prediction model of PD-L1 expression in NSCLC patients based on 18F-fluorodeoxy glucose (18F-FDG) positron emission tomography/conputed tomography (PET/CT) metabolic parameters and to evaluate its predictive value. METHODS: Retrospective collection of 18F-FDG PET/CT metabolic parameters, clinicopathological information and PD-L1 test results of 155 NSCLC patients from Inner Mongolia People's Hospital between September 2016 and July 2021. The patients were divided into the training group (n=117) and the internal validation group (n=38), and another 51 cases of NSCLC patients in our hospital between August 2021 and July 2022 were collected as the external validation group according to the same criteria. Then all of them were categorized according to the results of PD-L1 assay into PD-L1+ group and PD-L1- group. The metabolic parameters and clinicopathological information of patients in the training group were analyzed by univariate and binary Logistic regression, and a Nomogram prediction model was constructed based on the screened independent influencing factors. The effect of the model was evaluated by receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) in both the training group and the internal and external validation groups. RESULTS: Binary Logistic regression analysis showed that metabolic tumor volume (MTV), gender and tumor diameter were independent influences on PD-L1 expression. Then a Nomogram prediction model was constructed based on the above independent influences. The ROC curve for the model in the training group shows an area under the curve (AUC) of 0.769 (95%CI: 0.683-0.856) with an optimal cutoff value of 0.538. The AUC was 0.775 (95%CI: 0.614-0.936) in the internal validation group and 0.752 (95%CI: 0.612-0.893) in the external validation group. The calibration curves were tested by the Hosmer-Lemeshow test and showed that the training group (χ2=0.040, P=0.979), the internal validation group (χ2=2.605, P=0.271), and the external validation group (χ2=0.396, P=0.820) were well calibrated. The DCA curves show that the model provides clinical benefit to patients over a wide range of thresholds (training group: 0.00-0.72, internal validation group: 0.00-0.87, external validation group: 0.00-0.66). CONCLUSIONS The Nomogram prediction model constructed on the basis of 18F-FDG PET/CT metabolic parameters has greater application value in predicting PD-L1 expression in NSCLC patients.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Positron Emission Tomography Computed Tomography ; Lung Neoplasms/drug therapy* ; Fluorodeoxyglucose F18/therapeutic use* ; Nomograms ; Retrospective Studies ; B7-H1 Antigen/metabolism* ; Glucose/therapeutic use* ; Positron-Emission Tomography/methods*

Objective:To investigate the clinical effect of homemade adjustable mirabilite vest in patients with severe acute pancreatitis and supply reference for clinical nursing.Methods:This was a randomized controlled study. One hundred patients with acute severe pancreatitis admitted to Putuo Hospital, Shanghai University of Traditional Chinese Medicine from January 2021 to June 2022 were selected, and were divided into the pocket group and the vest group according to the order of admission with 50 cases in each group. The pocket group used traditional mirabilite bag for external application, the vest group used adjustable mirabilite vest for external application. The other treatment measures were the same for both two group. The comfort degree, itching severity and average length of hospital stay of these two groups were compared.Results:The basic data of the two groups were homogeneous. The difference were not statistically significant( P>0.05). After intervention, the comfort degree of the pocket group was (65.90 ± 7.95) points while the comfort degree of the vest group was (77.04 ± 5.96) points. The difference was statistically significant ( t = 7.93, P<0.01). The degree of pruritus was (12.72 ± 3.95) points in the pocket group and (8.00 ± 1.20) points in the vest group.The difference was statistically significant ( t = 8.08, P<0.05). The mean length of hospital stay in the pocket group was (15.86 ± 5.83) days and (11.02 ± 3.38) days in the vest group. The difference was statistically significant ( t = 5.08, P<0.01). Conclusions:When using topical mirabilite for patients with acute severe pancreatitis, the use of adjustable mirabilite vest can significantly improve patients′ comfort, reduce itching, and reduce the number of hospital days, which has the value of promotion and use.

Objective: To investigate the relationship between serum miR-199a-5p and miR-378a-3p levels and the recurrence of infants with proliferative facial hemangioma relapsed after propranolol withdrawal in infants. Methods: Ninety-three infants with proliferative facial hemangioma were selected, all of whom received propranolol treatment. The recurrence of the hemangioma after treatment was followed up, and the children were divided into a recurrence group (23 patients) and a nonrecurrence group (70 patients). Venous blood was collected before and after treatment, and the serum levels of miR-199a-5p and miR-378a-3p were detected by qRT-PCR, and the relationship between the serum levels of miR-199a-5p and miR-378a-3p and the recurrence of proliferative facial hemangioma relapsed after propranolol withdrawal in infants was analyzed. Results : The serum expressions levels of miR-199a-5p and miR-378a-3p in non-relapsed group were increased after treatment compared with before treatment (P < 0.05), and there was no significant difference in the levels of miR-199a-5p and miR-378a-3p in the serum of the recurrence group after treatment compared with before treatment (P > 0.05). After treatment, the levels of miR-199a-5p and miR-378a-3p in the serum of the recurrence group were lower than those of the nonrecurrence group (P < 0.05). After treatment, the serum levels of miR-199a-5p and miR-378a-3p in patients with Ⅲ ~Ⅳ Norm grade hemangioma were higher than those in patients with Ⅰ~Ⅱ Norm grade hemangioma (P < 0.05). Logistic regression analysis showed that the low expression of miR-199a-5p, low expression of miR-378a-3p and tumor grade Ⅰ~Ⅱ after treatment were risk factors for the recurrence of proliferative facial hemangioma after propranolol withdrawal in infants (P < 0.05). Conclusion Low serum levels of miR-199a-5p and miR-378a-3p are associated with the recurrence of proliferative facial hemangioma after propranolol withdrawal in infants.