Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

ObjectiveTo investigate the risk factors for pulmonary fungal infection in lung cancer patients， construct and validate a risk prediction model using available clinical data to predict the risk of pulmonary fungal infections in patients with lung cancer. MethodsWe conducted a retrospective study and collected information of 390 lung cancer patients treated at Zhongshan People's Hospital from January 2021 to March 2023. Demographic and clinical characteristics of the patients with and without pulmonary fungal infections were used to construct column line graphs to predict the occurrence of pulmonary fungal infections. All enrolled patients were randomly assigned to training set and internal validation set in the ratio of 7：3. For the modelling group， LASSO regression was applied to screen variables and select predictors， and multivariate logistic regression with a training set was used to construct the Noe column line graph model. The judgment ability of the model was determined by calculating the area under the curve （AUC）， and in addition， calibration analysis and decision curve analysis （DCA） were performed on the model. ResultsLASSO regression identified 14 potential predictive factors， and further logistic regression analysis showed that hepatic injury， surgery， anemia， hypoalbuminemia， illness course， invasive operation， hospital stay at least 2 weeks and glucocorticoid used for at least 2 weeks were independent predictors for the occurrence of pulmonary fungal infection in lung cancer patients. A predictive model was established based on these variables， with an AUC95%CI of 0.980 （0.973， 0.896） for the training set and an AUC95%CI of 0.956 （0.795， 1.000） for internal validation， indicating high discriminative ability. The calibration curves for both the training set and validation set were distributed along the 45°line， and the decision curve analysis （DCA） showed net benefit for threshold probabilities greater than 0.03. ConclusionsThe construction and validation of a predictive model for the risk of lung fungal infections in lung cancer patients will help clinical practitioners to identify high-risk groups and give timely intervention or adjust treatment decisions.

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective    To analyze the surgical results of patients with supracardiac total anomalous pulmonary venous connection (TAPVC) in a single pediatric cardiac center. Methods    A retrospective study was conducted on 98 pediatric patients with supracardiac TAPVC receiving surgical repair from 2014 to 2019 in our center. There were 64 males and 34 females with a median surgical age of 3.0 (1.5, 7.0) months and a median weight of 5.0 (4.0, 6.0) kg. Twenty-three (23.5%) patients had preoperative pulmonary vein obstruction. Ninety-two (93.9%) patients received conventional surgical repair, while six (6.1%) patients were treated with the sutureless technique. The Cox regression model was used to analyze the data. Results    The median follow-up time was 26.50 (5.75, 44.25) months. There were 9 (9.2%) deaths. Lower weight at the time of repair (P=0.013) and prolonged cardiopulmonary bypass time (P=0.007) were associated with mortality. Postoperative pulmonary vein obstruction was observed in 8 (8.2%) patients. Associated risk factors for postoperative pulmonary vein obstruction included lower weight at the time of repair (P=0.042) and prolonged cardiopulmonary bypass time (P=0.002). Conclusion    Surgical repair of supracardiac TAPVC has achieved satisfactory results in our center. Risk factors such as lower weight at the time of repair and prolonged cardiopulmonary bypass time are associated with a poor prognosis.

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m²), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m²) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m²)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.
Cohort Studies ; Glomerulonephritis, IGA/pathology* ; Humans ; Kidney Failure, Chronic/therapy* ; Plasma Exchange ; Prognosis ; Retrospective Studies ; Steroids/therapeutic use*

OBJECTIVE: To investigate the molecular mechanism in stable cell strains expressing Mini-hF9 gene with nonsense mutation. METHODS: Mini-hF9 gene and its nonsense mutants were transfected into HeLa cells independently, and stable cell strains were obtained after G418 resistance screening and monoclonal transformation. The altered splicing and protein expression of mRNA in Mini-hF9 gene in stable cell strains were detected by using RT-PCR and Western blot. RESULTS: The wild type and nonsense mutated human coagulation factor IX stable cell strains were constructed successfully, which were named HeLa-F9-WT, HeLa-F9-M1 and HeLa-F9-M2. Only normal splicing Norm was detected in the wild-type cell strain HeLa-F9-WT; Norm and Alt-S1 splicing were detected in HeLa-F9-M1; while Norm, Alt-S1 and Alt-S2 splicing were detected in HeLa-F9-M2. CONCLUSION The nonsense associated altered splicing (NAS) pathway, which generated alternately spliced transcripts, might be triggered in coagulation factor IX gene with nonsense mutation.
Codon, Nonsense ; Factor IX/metabolism* ; HeLa Cells ; Humans ; Mutation ; RNA Splicing ; RNA, Messenger/metabolism*

OBJECTIVE: To observe the short-term and long-term effects of moxibustion on plaque psoriasis of blood stasis, and to compare the curative effect between moxibustion and calcipotriol ointment. METHODS: A total of 80 patients with plaque psoriasis of blood stasis were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 4 cases dropped off). Both groups were given routine medical vaseline topical emollient basic treatment. In the observation group, moxibustion was applied to RESULTS: After treatment, the PASI scores in the both groups were lower than before treatment ( CONCLUSION Both moxibustion and calcipotriol ointment have good short-term effects on plaque psoriasis of blood stasis. Moxibustion has more advantages in reducing the recurrence rate of psoriasis, improving the main clinical symptoms of TCM and quality of life.
Acupuncture Points ; Humans ; Moxibustion ; Psoriasis/drug therapy* ; Quality of Life ; Treatment Outcome

Objective    To explore risk factors associated with mortality and restenosis after the surgery for congenital pulmonary venous stenosis (CPVS) combined with congenital heart disease. Methods    From May 2007 to August 2019, 58 patients received surgical relief of CPVS combined with congenital heart disease, including 24 males and 34 females, aged 17.2±26.3 months, weighing 8.8±8.2 kg. Endpoints were death and restenosis, and the risk factors were analyzed. A univariate and multivariate risk analyses were performed. Results    Preoperative pulmonary venous stenosis severity score (PVSSS) was 4.5±2.7. Average pulmonary vein counts with CPVS was 1.9±1.0. There were 2 (3.4%) early deaths. The mean follow-up time was 2-145 (49.8±40.0) months. The 1-, 2-, 3- and 5-year overall survival rates were 86.7%, 81.3%, 78.5% and 73.6%, respectively, and the pulmonary venous restenosis-free rates were 79.6%, 68.5%, 68.5% and 68.5%, respectively. Preterm birth was an independent risk factor for mortality. The pulmonary venous peak flow rate ≥ 1.2 m/s at discharge was an independent risk factor for mortality and restenosis. Conclusion    The prognosis of CPVS is still poor. Postoperative residual stenosis at discharge is an independent risk factor for death and restenosis.