ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Objective:To study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.

Objective:To investigate the clinical efficacy of minimally invasive double anchoring combined with percutaneous kyphoplasty (PKP) for Kümmell disease.Methods:The clinical data of 24 patients with Kümmell disease who were treated with minimally invasive double anchoring combined with PKP in Cangzhou People's Hospital from October 2022 to March 2024 were retrospectively analyzed. Among them, there were 2 T 10 vertebrae, 5 T 11 vertebrae, 7 T 12 vertebrae, 6 L 1 vertebrae, and 4 L 2 vertebrae. There were 6 males and 18 females. The average age was 72.05±4.52 years (range, 66-80 years). The bone mineral density T value was -3.41±0.77 (range, -2.5-4.5). The stages of Li's Kümmell disease included 13 cases of stage II and 11 cases of stage III. The operation time, intraoperative blood loss, and volume of bone cement injected were recorded. The vertebral index, vertebral angle and Cobb angle of diseased segment were measured before and after operation. The visual analogue scale (VAS) was used to assess the degree of pain, the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) low back pain scale were used to assess spinal function. The Medical Outcome Study short form 36 item health survey (SF-36) was used to assess the general health status of the patients. The postoperative symptom recovery was evaluated by Odom criteria. Results:The mean operative time of the 24 patients was 35.32±6.86 min, the injected volume of bone cement was 4.39±1.72 ml, and the intraoperative blood loss was 16.56±5.21 ml. All patients were followed up for 10 to 14 months, with an average of 11.7 months. Postoperative CT examination showed that the screw positions were satisfactory, and no loosening or displacement of bone cement mass occurred. On the first day after surgery, the vertebral body index, vertebral body angle and Cobb angle of diseased segment were 77.71%±2.75%, 12.40°±1.53° and 25.77°±4.49°, respectively, which represented significant improvements from the preoperative values of 43.09%±5.66%, 22.12°±2.92° and 46.98°±5.68° before surgery ( P<0.05). At the last follow-up, the values were 76.18%±2.32%, 12.41°±2.53°, 26.14°±4.87°, respectively, which were significantly improved compared with those before surgery ( P<0.05), but there was no statistical significance compared with the first day after surgery ( P>0.05). The VAS, ODI and JOA scores on the first day after surgery were 2.11±0.87 points, 22.46±5.49 points and 27.68±2.45 points, respectively, which were significantly improved compared with those before surgery 7.50±0.98 points, 76.25±8.56 points and 14.96±4.91 points ( P<0.05). At the last follow-up, the values were 2.26±0.88, 23.87±3.25 and 26.58±2.77, respectively, which were significantly improved compared with those before surgery ( P<0.05), and there was no statistical significance compared with the first day after surgery ( P>0.05). All 24 patients completed SF-36 scale assessment, and the results showed that there were statistically significant differences in physiological function, physiological role, physical pain, general health status, social function scores and mental health between the patients before surgery and the last follow-up ( P<0.05), while there were no statistically significant differences in vitality and emotional function ( P>0.05). At the last follow-up, the Odom criteria showed excellent results in 18 cases, good in 4 cases, and fair in 2 cases. Conclusions:The application of minimally invasive double anchoring (single nail fixation) combined with PKP in the treatment of Kümmell disease can effectively prevent the loosening and displacement of bone cement masses, and the fixation effect is satisfactory, which can restore the height of the injured vertebrum, reduce kyphosis and improve spinal function. The clinical symptoms of the patients were significantly improved, and the quality of life was enhanced.

After the wooden shipwreck was recovered from the marine underwater environment,the wooden components undergo varying degrees of degradation,therefore,accurately determining the extent of degradation is a fundamental scientific issue for implementing effective preservation strategies.In this work,the wooden remains of Pinus massoniana excavated from the"Nanhai No.1"shipwreck(Southern Song Dynasty)were investigated and compared with the modern wood to discriminate the degradation levels of archaeological wood using attenuated total reflection Fourier transform infrared(ATR-FTIR)spectroscopy.The residual sugar content within wood cell walls was determined using a non-invasive automated microscale ATR-FTIR method to extract chemical information from the wood tangential section.Microstructural characterization of wood samples was conducted by super depth of field microscopy and scanning electron microscopy.FTIR spectral analysis was performed to evaluate the degradation state and elucidate changes in cellulose crystallinity.Finally,the combination of FTIR spectroscopy with the sparse partial least squares discriminant analysis(sPLS-DA)model facilitated the rapid discrimination of degradation levels in shipwreck archaeological wood,and the performance of the model was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).The results showed that the higher the degree of wood degradation,the lower the residual sugar content in the wood cell wall,and the residual glucose content of highly degraded wood was only 4.7％.Significant differences were observed in both the tangential section microstructure and FTIR characteristic absorption patterns across degradation levels,and as the degradation advanced,progressive cell wall loosening occurred alongside selective removal of polysaccharide components,and the relative lignin content was increased,resulting in an elevated A1509/A1370 ratio in FTIR spectra.The sPLS-DA model achieved excellent discrimination performance with AUC values exceeding 0.9,confirming that the combination of FTIR spectroscopy with sPLS-DA enabled accurate assessment of degradation levels in shipwreck archaeological wood.This study developed a rapid and accurate methodology for assessing degradation levels in shipwreck archaeological wood based on microscale ATR-FTIR spectroscopy,which would help to promote the accurate assessment of the preservation state of waterlogged wooden artifacts.

Objective To assess the efficacy and safety of bronchial arterial chemoembolization(BACE)combined with tislelizumab for advanced non-small cell lung cancer(NSCLC).Methods A total of 30 patients in First Affiliated Hospital of Zhengzhou University with stage Ⅲ-Ⅳ NSCLC from December 2021 to August 2022 were enrolled in this study.All the patients received BACE,which was followed by 200 mg tislelizumab once every 3 weeks until the disease progressed,or the patient developed intolerable adverse effects,or the investigator decided to terminate this drug treatment.The primary study endpoint was progression-free survival(PFS),and the secondary study endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),safety,and quality of life(QoL).Results The median follow-up time was 12 months(range of 1.5-12 months),the median PFS was 10.5 months(95％CI:7.8-13.2 months),and the median OS was not available.The 3-month,6-month,and 12-month ORRs were 63.3％(95％CI:43.9％-80.1％),56.7％(95％CI:37.4％-74.5％),and 30.4％(95％CI:13.2％-52.9％)respectively.The 3-month,6-month,and 12-month DCRs were 80％(95％CI:61.4％-92.3％),76.7％(95％CI:57.7％-90.1％),and 47.8％(95％CI:26.8％-69.4％)respectively.The expression ratio of PD-L1 ≥50％(HR=0.29,P=0.039),tumor having a single feeding artery(HR=0.35,P=0.028),and completion of＞10 cycles of tislelizumab therapy(HR=0.42,P=0.064)were the protective factors for PFS.No ≥grade Ⅲ treatment-related adverse events(TRAEs)occurred.The common below grade Ⅱ TRAEs were nausea,fever,and cough.After one cycle of treatment,the patient's QoL,including overall quality of life,physical functioning,and emotional functioning,was significantly improved.Conclusion For the treatment of patients with advanced NSCLC,BACE plus tislelizumab has satisfactory clinical efficacy and safety.

Objective To investigate the expression and significance of CD4+CD25+regulatory T cells(CD4+CD25+Treg)and soluble CD30(sCD30)in peripheral blood of lymphoma patients.Methods A total of 83 lymphoma patients admitted to Beijing Aerospace General Hospital from January 2018 to December 2022 were selected as the research subjects,and their peripheral blood CD4+CD25+Treg and sCD30 expressions were statistically analyzed.Spearman analysis was used to investigate the correlation between peripheral blood CD4+CD25+Treg and sCD30 expressions and bone marrow infiltration.At the same time,the research subjects were divided into an infection group(n=26)and a non-infection group(n=57)according to the presence or absence of infection after rituximab chemotherapy.The expressions and differences of peripheral blood CD4+CD25+Treg and sCD30 in the two groups were compared,and the receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to analyze the predictive efficacy.Results The expression of CD4+CD25+Treg and sCD30 in peripheral blood of patients with bone marrow infiltration was higher than that of patients without bone marrow infiltration in the research group(P<0.05);the expression of CD4+CD25+Treg and sCD30 in peripheral blood of lymphoma patients was positively correlated with bone marrow infiltration(r=0.612,0.634,P<0.05);the expression of Tregs and sCD30 in peripheral blood of the infection group after chemotherapy was higher than that of the non-infection group,and the difference was higher than that of the non-infection group(P<0.05);the ROC curve showed that the combined prediction of the difference of CD4+CD25+Treg and sCD30 in peripheral blood for the infection after chemotherapy in lymphoma patients had an AUC of 0.916(0.834～0.965),which was superior to single prediction.Conclusion The high expression of CD4+CD25+Treg and sCD30 in peripheral blood of lymphoma patients is positively correlated with bone marrow infiltration.Combined testing can improve the predictive efficacy of infection after chemotherapy and guide clinical diagnosis and treatment.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.