Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

[Objective] To evaluate the clinical application value of intrauterine perfusion with platelet-rich plasma (PRP) combined with in vitro fertilization-frozen-thawed embryo transfer (IVF-FET) in patients with chronic endometritis (CE). [Methods] A randomized controlled trial (RCT) was conducted, enrolling 60 CE patients undergoing artificial cycle frozen embryo transfer at our hospital from January 2022 to January 2024. Participants were randomly divided into three groups: Group A (routine frozen embryo transfer, n=20), Group B (routine frozen embryo transfer + one PRP intrauterine perfusion, n=20), and Group C (routine frozen embryo transfer + two PRP intrauterine perfusions, n=20). Endometrial thickness during the transformation and transplantation phases, uterine artery pulsatility index (PI), resistance index (RI), systolic peak velocity/end-diastolic velocity (S/D) ratio during transplantation, serum levels of IL-2, IL-4, IL-6, IL-10, and TNF-α during transplantation, as well as biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and early miscarriage rate were compared across groups. [Results] No significant differences in endometrial thickness were observed among the three groups during the transformation phase (P>0.05). During the transplantation phase, endometrial thickness in Groups C and B was significantly higher than in Group A[9.54 (8.96-10.22) and 8.90 (8.34-9.72) vs 8.37 (7.89-8.75) mm, P<0.05], with Group C showing greater thickness than Group B (Z=3.733, P<0.05). Endometrial thickness in Groups C and B during transplantation was significantly increased compared to their respective transformation phases (Z=2.191, 2.462; P<0.05). Groups C and B exhibited lower PI, RI, and S/D values than Group A[PI:1.87 (1.77-1.97), 1.94 (1.88-2.15) vs 2.43 (2.35-2.49); RI:0.75 (0.73-0.77), 0.78 (0.75-0.81) vs 0.84 (0.83-0.86); S/D:2.61 (2.33-3.42), 3.01 (2.20-3.93) vs 3.72 (3.06-4.49); P<0.05]. Group C demonstrated lower PI and RI than Group B (P<0.05). IL-2 levels in Groups C and B were higher than in Group A[3.88 (2.71-5.01), 3.59 (2.73-4.38) vs 3.16 (2.11-3.25) ng/L, P<0.05], while IL-4, IL-6, IL-10, and TNF-α levels were significantly lower (IL-4: Z=1.428, 2.421; IL-6: Z=1.754, 2.435; IL-10: Z=1.754, 2.854; TNF-α: Z=1.961, 1.765; P<0.05). Group C had lower IL-6 levels than Group B (Z=3.976, P<0.05). Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate in Group C were significantly higher than in Group A (75% vs 40%, 70% vs 35%, 60% vs 20%, P<0.05). No significant differences in early miscarriage rates were observed among the groups (χ²=3.750, P>0.05). [Conclusion] Intrauterine autologous PRP perfusion in CE patients enhances pregnancy and live birth rates, improves pregnancy outcomes post-FET, and demonstrates superior efficacy in endometrial repair and receptivity with two PRP perfusions compared to a single perfusion. This provides a safe and effective therapeutic option for optimizing outcomes in CE patients with prior implantation failure.

Objective:To evaluate the effect of Qishi Tongguan Prescription on pregnancy outcomes after interventional recanalisation in patients with tubal infertility (TFI).Methods:This was a retrospective study based on real-world and propensity score matching. Totally 260 patients with TFI from January 2020 to October 2021 in Shuguang Hospital of Shanghai University of Traditional Chinese Medicine and Maternal and Child Health Hospital of Pudong New Area were selected as observation subjects, and were divided into 123 cases in the TCM combination group and 137 cases in the control group based on whether they were treated with Qishi Tongguan Prescription in combination with interventional revascularization. Propensity score matching (PSM) was used as a covariate to obtain a new sample of inter group covariate equilibrium, and confounding factors that may affect the pregnancy outcome of TFI patients undergoing interventional recanalization surgery were used as covariates. The intrauterine pregnancy rate, ectopic pregnancy rate, biochemical pregnancy rate, early abortion rate and adverse reactions of the two groups of patients within 12 months of follow-up were compared, and the influence of TFI intervention and recanalization combined with Qishi Tongguan Prescription on intrauterine pregnancy rate was evaluated.Results:Age, years of infertility, type of infertility, history of miscarriage, history of ectopic pregnancy, history of biochemical pregnancy, history of uterine surgery, history of pelvic laparotomy, and degree of tubal patency had an effect on whether intrauterine pregnancy was achieved after interventional reversal in patients with TFI ( P<0.05), with age [ OR (95% CI) was 0.843 (0.769, 0.926)], history of pelvic laparotomy [ OR (95% CI) was 0.477 (0.248, 0.920)] and the degree of tubal obstruction [ OR (95% CI) was 0.152 (0.046, 0.500)] were independent factors ( P<0.01 or P<0.05). 81 patients were seen in each of the 2 groups after PSM, of whom the intrauterine pregnancy rates in the combined herbal group at 9 and 12 months after recanalisation were 48.1% (39/81) and 58.0% (47/81) respectively, compared with 32.1% (26/81) and 35.8% (29/81) in the control group, with statistical significance between the 2 groups ( χ2 values of 4.34 and 8.03, respectively, P<0.01); there was no statistical significance in the ectopic pregnancy rate, biochemical pregnancy rate and early abortion rate between the 2 groups ( P>0.05). There were no significant adverse reactions during the treatment. Conclusion:Qishi Tongguan Prescription combined with interventional recanalization can effectively improve the intrauterine pregnancy rate and shorten the waiting time for pregnancy in patients with TFI with higher safety.

Objective To investigate the clinical features of pediatric Kawasaki disease(KD)complicated with pleural effusion(PE)and construct a clinical prediction model.Methods A retrospective review was conducted on clinical data of 462 children with KD from June 2017 to June 2023.Eleven KD children with PE were selected as the KD-PE group,and 118 patients without PE were selected as the KD control group.Using propensity score matching,the clinical data including clinical manifestation,auxiliary examination,treatment process and complications were collected and analyzed.Univariate and Lasso-Logistic regression were used to analyze influence factors of PE in children with KD.A line chart model for predicting KD-PE was constructed,and the prediction efficiency of the model was evaluated.Results The respiratory symptoms were generally mild in the KD-PE group,with 10 cases exhibiting mild PE.Two variables of C-reactive protein(CRP,OR=1.045,95%CI:1.009-1.082)and albumin(ALB,OR=0.755,95%CI:0.591-0.964)were screened out by Lasso regression and multi-factor Logistic regression to construct the prediction model.The regression equation was Logit(P)=2.221+0.044×CRP-0.281×ALB.The area under the ROC curve of the prediction model was 0.957(95%CI:0.911-1.000),and the Hosmer-Lemeshow test showed that the curve of the calibration model was well coincident with the curve of the actual model(χ2=4.320,P=0.827).The evaluation model using clinical decision curve and clinical impact curve had good clinical applicability.Conclusion KD complicated with PE in children is rare,elevated CRP is a risk factor for KD-complicated PE,and elevated ALB is a protective factor.The model has higher accuracy,discriminatory power and net benefit.

Background and Objectives: Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction ofarticular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation. Methods: and Results: Real-time reverse transcription–polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3’-untranscribed region. Conclusions These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.

OBJECTIVE: To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old. METHODS: A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa. RESULTS: A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%). CONCLUSIONS The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.
Humans ; Infant ; Child ; Prospective Studies ; Bacterial Infections ; C-Reactive Protein ; Hospitals ; Interleukin-6 ; Procalcitonin

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Tongue diagnosis is an indispensable objective basis for TCM diagnosis and treatment of epidemic diseases.To understand its application in an epidemic situation and to support in the diagnosis and treatment of infectious diseases using traditional Chinese medicine,the tongue image APP was implemented in this study to monitor the tongue image features of patients with new coronavirus pneumonia.It has been discovered through practice that the tongue image APP enables medical professionals to objectively,conveniently,quickly,and flexibly collect the patient's tongue image.It has also been discovered through the analysis of the tongue image characteristic data that the tongue image APP can,to a certain extent,objectively reflect the general law of the tongue image characteristics of the new crown pneumonia.According to the tongue image data gathered by the Tongue Image APP,Xinguan pneumonia patients'tongues were typically red,their fur was typically white,yellow,or both white and yellow,and they had a greater amount of thick and greasy fur.Nevertheless,there are still several issues with the Tongue APP application that have been noted:①The consistency of tongue shape and coating was poor;for instance,the inconsistency rate between a thin and fat tongue was as high as 62.96%;②The tongue image analysis index in the APP is still mostly a qualitative index,and the degree of discriminating is insufficient.The results of this study demonstrate that the tongue image information of different ages,sexes,disease classifications,and onset times does not reflect obvious differences and certain rules.③The tongue image characteristic indexes gathered by the tongue image APP are insufficient and do not include information on glossiness of tongue image(such as dark tongue)and tongue state.To promote the adoption of the tongue image APP and better support the prevention and treatment of epidemic diseases by traditional Chinese medicine,we should fully integrate modern advanced science and technology,improve the short videos of tongue coating,quantification of qualitative indicators,comprehensive collection of tongue image characteristic indicators,etc.

Magnetic Resonance Imaging(MRI)technology can directly show the changes of brain network and explain the central mechanism of Tai Chi remodeling of brain structure and function.In this paper,we collected the domestic and foreign research on the influence of Tai Chi movement on the brain network by using MRI technology,and combed it from the perspective of brain structure and function changes.The results revealed that Tai Chi may promote memory function,cognitive flexibility,inhibitory control,and working memory capacity by remodeling the structure and function of the medial temporal lobe and prefrontal cortex in older adults,which may be a potential central mechanism for Tai Chi to improve memory and cognitive control in the elderly.However,there are some problems in the current research,such as small sample size,insufficient long-term follow-up,and difficult evaluation of exercise intensity.It is necessary to carry out large-sample and long-term detailed research to further verify the current research results.