Objective To compare the clinical efficacy of neuroendoscope-assisted evacuation and navigation-assisted puncture drainage in treating thalamic hemorrhage breaking into the ventricle. Methods A retrospective analysis was conducted on the clinical data of 93 patients with thalamic hemorrhage breaking into the ventricle at Taihe Hospital of Wannan Medical College between January 2022 and February 2024. The patients received neuroendoscope-assisted removal of thalamic hematoma combined with contralateral extraventricular drainage (n＝44, neuroendoscope group) and navigation-assisted thalamic hematoma puncture drainage combined with contralateral extraventricular drainage (n＝49, navigation group), respectively. The treatment efficacy, surgical situation, and prognosis between the two groups were compared. Results The neuroendoscope group had longer operation duration, more intraoperative blood loss, higher hospitalization costs than the navigation group (P＜0.05). The neuroendoscope group had higher hematoma clearance rate 3rd after surgery and shorter length of stay than the navigation group (P＜0.05). There was no significant difference in the incidence of intracranial infection after surgery between the two groups. The neuroendoscope group had higher Glasgow coma scale (GCS) score at 1 week after surgery and Glasgow outcome scale (GOS) score at 3 months after surgery (P＜0.01). Conclusions Compared with navigation-assisted puncture, neuroendoscope-assisted evacuation can improve the thalamic hemorrhage clearance rate, shorten the length of stay, and improve the prognosis of patients.

ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

Objective: To isolate a lytic phage targeting K. pneumoniae type K39 from untreated sewage and systematically analyze its biological characteristics and genomic information. Methods: The bacteriophage of K. pneumoniae K39 Kp 1000 was identified based on the sequence of the capsular polysaccharide gene. It was isolated and purified using the double agar plate method. The morphology of the phage was observed through negative staining and transmission electron microscopy,and its bacteriophage spectrum was evaluated by phagocytosis. The biological characteristics of the bacteriophage were assessed by determining the optimal multiplicity of infection(MOI),constructing a one-step growth curve,and conducting temperature and pH tolerance tests. Finally,the phage DNA was extracted,and its whole genome was sequenced using the Illumina Hi Seq2000 sequencing platform. The sequencing results were then annotated and analyzed. Results: A lytic phage specifically targeting K. pneumoniae type K39was successfully isolated and named IME330. Transmission electron microscopy showed that the head diameter of the phage was(75 ± 1) nm and the tail length was(185 ± 1) nm. The lytic spectrum analysis revealed that IME330 lysed K. pneumoniae type K39,demonstrating a narrow host range and high specificity. The optimal multiplicity of infection(MOI) was 0. 1,The lysis amount reached 168 PFU/cell. Physicochemical experiments indicated that IME330 exhibited strong tolerance to high temperatures and a broad p H range(pH 4-10). Genomic analysis demonstrated that the IME330 genome had a length of 144,245 bp,a molecular weight of 46,463 MDa,G +C content of 44. 8%,and encoded 320 open reading frames(ORFs). Conclusion IME330 is a novel lytic K.pneumoniae phage belonging to the order Caudovirales. This phage exhibits strong tolerance to physicochemical factors(e. g.,temperature,acidic/alkaline conditions) and demonstrates high lytic activity,while its lytic spectrum remains narrow with strict host specificity.

This study utilized data from the non-communicable diseases (NCDs) Progress Monitor Reports (2015, 2017, 2020, 2022) released by World Health Organization (WHO) to analyze the implementation of NCDs prevention and control policies in China from 2014 to 2021 through descriptive statistical method, aiming to provide evidence for strengthening national NCDs strategies. The analysis focuses on WHO-recommended ‘best buys’ policies for NCDs prevention and control, covering 10 categories (18 interventions): national NCDs targets, mortality data, risk factor surveys, national integrated NCDs policies/strategies/action plans, tobacco demand-reduction measures, harmful use of alcohol reduction measures, unhealthy diet reduction policies, physical activity campaigns, national clinical guidelines for cancer/CVD/diabetes/CRD management, and drug therapy/counselling for cardiovascular diseases. In accordance with the WHO′s NCDs progress monitor scoring methodology, policies are assigned 1.0 point for full implementation, 0.5 points for partial implementation, and 0 points for non-implementation or missing data, with a maximum total score of 18.0 points. The analytical metrics encompass the policy implementation score, implementation rate, and period-on-period implementation growth rate. The results showed that China′s total policy implementation scores for NCDs prevention and control in 2014, 2016, 2019, and 2021 were consistently higher than the global average (8.5, 10.5, 9.5, 9.5 vs 6.7, 8.3, 8.6, 8.6). From 2014 to 2021, the total score increased by 1.0 point, and the implementation rate improved by 8.9%. From 2014 to 2016, China′s total policy implementation score rose from 8.5 to 10.5, primarily driven by improvements in tobacco tax increases and unhealthy diet reduction measures (salt reduction, restrictions on high-fat foods, and regulation of breast-milk substitute sales). However, this progress was partially offset by a decline in scores for physical activity campaigns. From 2016 to 2019, the total score decreased to 9.5, largely due to lower scores in harmful use of alcohol reduction measures (alcohol taxation and advertising bans). From 2019 to 2021, the total score remained stable, with increases in marketing to children restrictions balanced by declines in scores for drug therapy/counselling for cardiovascular diseases. In 2021, China′s total policy implementation score (9.5) exceeded the global average (8.6) but fell below the G20 average (11.2). Significant gaps remained compared to top-performing G20 countries such as Turkey (16.5), particularly in tobacco control and restrictions on harmful alcohol use. In conclusion, from 2014 to 2021, China′s total policy implementation score for NCDs prevention and control consistently exceeded the global average, demonstrating an upward trend, and various NCDs prevention and control policies have been continuously improved.

Background Water serves as an indispensable resource for human survival and constitutes one of the primary means through which humans are exposed to environmental chemicals. Consequently, the safety of drinking water is critical to safeguarding public health. Objective To analyze the levels of the 10 metal/metalloid indicators [Al, Fe, Mn, Cu, Zn, As, Cd, Cr(VI), Pb, and Hg] in drinking water from a region of the Fuchun River Basin, and to evaluate the health risks in drinking water through oral ingestion. Methods In accordance with the national Standard Examination Method for Drinking Water – Part 2: Collection and Preservation of Water Samples (GB/T 5750-2006 and GB/T 5750-2023), a total of 2016 drinking water samples were collected from urban and rural water supply systems in a region of the Fuchun Basin from 2017 to 2024. Two batches of water samples were collected annually during the dry and wet seasons, with each batch comprising 72 samples from the urban water supply system and 54 samples from the rural water supply system. These samples were analyzed according to the Standard Examination Method for Drinking Water – Part 6: Metal and Metalloid Indicators (GB/T 5750-2006 and GB/T 5750-2023) and the results were compared with the limits specified in the Standards for Drinking Water Quality (GB 5749-2022). Health risks were evaluated using the U.S. Environmental Protection Agency (EPA) health risk assessment model. Results All tested metal/metalloid elements in the drinking water samples of the area met the national standards. The results of risk assessment showed that the non-carcinogenic risks associated with oral intake of drinking water, ranked from highest to lowest, were as follows: As>Cr(VI)>Pb>Cd>Hg>Mn>Cu>Zn>Fe>Al, with values of 4.55×10⁻², 2.79×10⁻², 2.06×10⁻², 1.20×10⁻², 4.95×10⁻³, 4.58×10⁻³, 2.85×10⁻³, 1.95×10⁻³, 1.52×10⁻³, and 9.21×10⁻⁴, respectively. The non-carcinogenic risk of each indicator was less than 1, which suggested no potential risk to population health. The carcinogenic risks ranked as Cr(VI)>As>Cd>Pb, with values of 4.18×10⁻⁵, 2.05×10⁻⁵, 3.85×10⁻⁶, and 2.45×10⁻⁷, respectively. The carcinogenic risks of Cr(VI), As, and Cd were between 10⁻⁶ and 10⁻⁴, which suggested an acceptable carcinogenic risk, while the carcinogenic risk of Pb was relatively negligible. Children's total non-carcinogenic/total carcinogenic risks were comparable to those of adult males, both higher than those of adult females. Additionally, rural areas exhibited higher non-carcinogenic/carcinogenic risks for Cr(VI), while those risks for As and Pb were lower than those in urban water samples, and those risks for Cd were comparable between the two. Conclusion The concentrations of the 10 metal/metalloid indicators in drinking water from the studied region in the Fuchun River Basin comply with the national standards from 2017 to 2024. There is a certain carcinogenic risk associated with oral intake of drinking water, but it is still within the acceptable range. In terms of non-carcinogenic risk, no potential threat to population health is anticipated.

Objective : To investigate the effect of laminarin(LAM) on nonproliferative diabetes retinopathy by high throughput sequencing(RNA-seq). Methods : The diabetes model was established by intraperitoneal injection of streptozotocin(STZ), and the effect of LAM on diabetic mice was observed.C57BL/6 mice were randomly divided into three groups: Control group, Model group, and LAM group, with 8 mice in each group. After 8 weeks of modeling, the LAM group received a 4-week intraperitoneal injection of LAM treatment. Changes in blood glucose and body weight of the three groups of mice were recorded, HE staining was performed to examine retinal lesions, and RNA-seq was used to identify differentially expressed genes(DEGs) in diabetic retinopathy(DR) under the action of STZ and LAM. Results : STZ successfully established the model of DR, and LAM reduced the blood sugar in diabetic mice to a certain extent and improved the pathological morphology of retinal structural looseness in diabetic mice. After RNA-seq analysis of DEGs, it was found that there were a total of 214 DEGs in the retina of the Model group mice compared to the Control group. Enrichment analysis revealed that DR could exacerbate the lesions through the PI3K Akt signaling pathway. There were a total of 42 DEGs in the retina of the Model group and LAM group mice, and enrichment showed that LAM improved the lesions through the neutrophil extracellular trap pathway. Early growth response factor 1(Egr1), FBJ osteosarcoma oncogene(Fos), nuclear receptor subfamily 4A member 1(Nr4a1), and salt-induced kinase 1(Sik1) were regulated by STZ, and LAM significantly regulated their expression, which might be closely related to LAM′s treatment of diabetic retinopathy. Conclusion DEGs can exacerbate the severity of diabetic retinopathyviathe PI3K-Akt signaling pathway. LAM can mitigate diabetic retinopathyviathe neutrophil extracellular trap pathway. Egr1, Fos, Nr4a1, and Sik1 are key genes involved in LAM treatment of STZ-induced DR.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

OBJECTIVE: To review and summarize the research progress on repairing segmental bone defects using three-dimensional (3D)-printed bone scaffolds combined with vascularized tissue flaps in recent years. METHODS: Relevant literature was reviewed to summarize the application of 3D printing technology in artificial bone scaffolds made from different biomaterials, as well as methods for repairing segmental bone defects by combining these scaffolds with various vascularized tissue flaps. RESULTS: The combination of 3D-printed artificial bone scaffolds with different vascularized tissue flaps has provided new strategies for repairing segmental bone defects. 3D-printed artificial bone scaffolds include 3D-printed polymer scaffolds, bio-ceramic scaffolds, and metal scaffolds. When these scaffolds of different materials are combined with vascularized tissue flaps ( e.g., omental flaps, fascial flaps, periosteal flaps, muscular flaps, and bone flaps), they provide blood supply to the inorganic artificial bone scaffolds. After implantation into the defect site, the scaffolds not only achieve structural filling and mechanical support for the bone defect area, but also promote osteogenesis and vascular regeneration. Additionally, the mechanical properties, porous structure, and biocompatibility of the 3D-printed scaffold materials are key factors influencing their osteogenic efficiency. Furthermore, loading the scaffolds with active components such as osteogenic cells and growth factors can synergistically enhance bone defect healing and vascularization processes. CONCLUSION The repair of segmental bone defects using 3D-printed artificial bone scaffolds combined with vascularized tissue flap transplantation integrates material science technologies with surgical therapeutic approaches, which will significantly improve the clinical treatment outcomes of segmental bone defect repair.
Printing, Three-Dimensional ; Tissue Scaffolds ; Humans ; Surgical Flaps/blood supply* ; Tissue Engineering/methods* ; Plastic Surgery Procedures/methods* ; Bone and Bones/surgery* ; Biocompatible Materials ; Bone Regeneration ; Bone Transplantation/methods* ; Bone Substitutes ; Osteogenesis