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.

OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group， model group， positive control group （insulin glargine）， Zuogui pill low-， medium- and high-dose groups （4.725， 9.45， 18.9 g/kg）. In addition to the blank group， streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy， each group was given relevant medicine and distilled water intragastrically， once a day. After 21 days of birth， the body weight and body length of offsprings were recorded， and the area under the curve （AUC） was calculated through a glucose tolerance test. After 22 days of birth， fasting blood glucose （FBG）， fasting insulin （FINS） levels in serum， insulin sensitivity index （ISI）， and homeostasis model assessment of insulin resistance （HOMA-IR） were measured， and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics， and protein and mRNA expression levels of apolipoprotein A1（ApoA1）， solute carrier family 27 member 1 （Slc27a1）， kininogen 1（Kng1） and sodium/potassium-transporting ATPase subunit alpha 2 （Atp1a2）， solute carrier family 7 member 5 （Slc7a5）， solute carrier family 3 member 2 （Slc3a2）， bile acid-coenzyme A： amino acid N- acyltransferase （Baat）， eukaryotic translation initiation factor 2 subunit gamma （Eif2s3） were detected. RESULTS Compared with the model group， the body weight， body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased （P＜0.05）， while the glucose tolerance and islet cell proliferation were significantly improved， and the AUC， FBG， FINS and HOMA-IR were significantly decreased （P＜0.05）. There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus，involving multiple pathways such as peroxisome proliferator-activated receptor （PPAR）， cyclic guanosine monophosphate-protein kinase G （cGMP-PKG）， fat digestion and absorption， and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1， Slc27a1， Kng1， Atp1a2， Slc7a5， Slc3a2， Baat， and Eif2s3. Among them， compared with the model group， protein and mRNA expressions of Slc7a5， Slc3a2， and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated （P＜0.05）； protein and mRNA expressions of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 were all significantly down-regulated （P＜0.05）. CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5， Slc3a2， and Baat and the down-regulation of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 expressions in the PPAR， cGMP-PKG， fat digestion and absorption， and bile secretion pathways.

Cancer represents a significant disease that profoundly impacts human health and longevity. Projections indicate a 47% increase in the global cancer burden by 2040 compared to 2020, accompanied by a further rise in the associated economic burden. Consequently, there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer. Natural products (NPs) play a crucial role in the identification and development of anticancer therapeutics. This study identified ustusolate E (UE) and its analog 11α-hydroxy-ustusolate E (HUE) from strain Aspergilluscalidoustus TJ403-EL05, and examined their antitumor activities and mechanisms of action. The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells), induced irreversible DNA damage, blocked the cell cycle at the G₂/M phase, and further induced apoptosis in tumor cells. To the best of the authors' knowledge, this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms. The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
Humans ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology* ; Sesquiterpenes/pharmacology* ; Aspergillus/chemistry*

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Objective: To determine the clinical efficacy of platelet-rich plasma (PRP) injection combined with warm acupuncture and moxibustion for treating patients with knee osteoarthritis and cold dampness obstruction syndrome. Methods: One hundred and twenty-eight patients with knee osteoarthritis and cold dampness obstruction syndrome who visited the Rehabilitation Department and Orthopedics Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to March 2024 and who met the inclusion and exclusion criteria were randomly divided into an experimental (n=64) and control group (n=64) using the random number table method. The experimental group was treated with PRP injection combined with warm acupuncture and moxibustion, whereas the control group was treated with normal saline injection combined with warm acupuncture and moxibustion treatment. PRP and normal saline injections were administered once every two weeks, a total of four times. Patients were treated with warm acupuncture and moxibustion once a day, six times a week, for four consecutive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Traditional Chinese Medicine (TCM) syndrome, visual analog scale (VAS), and Lysholm scores were determined before treatment, at week 4 and week 8 of treatment, and week 16 of follow-up. Serum interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), bone gla protein(BGP), and cartilage oligomeric matrix protein (COMP) levels were compared between the two groups before and after 8 weeks of treatment. The clinical efficacy and safety indicators between the two groups were also compared. Results: There was no statistical difference in baseline data such as gender, age, disease duration, and body mass index between the two groups of patients. Compared with before treatment, both groups showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm scores at 4, 8, and 16 weeks after treatment. After treatment, serum IL-6, MMP-3, TNF-α, and COMP levels decreased, whereas serum OPG and BGP levels increased (P<0.05). Compared with the control group, patients in the experimental group showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm score at 4, 8, and 16 weeks after treatment. Compared with the control group, patients in the experimental group showed decreased serum IL-6, MMP-3, TNF-α, and COMP levels and an increase in serum OPG and BPG levels after treatment (P<0.05). The total effective rate of the experimental group was 91.94%, higher than that of the control group (81.97%; P<0.05). Conclusion PRP injection combined with warm acupuncture and moxibustion can improve various TCM symptoms, improve knee joint function and bone metabolism, and reduce inflammation in patients with knee osteoarthritis and cold dampness obstruction syndrome.

Objective:To identify and validate secreted effector proteins of Chlamydia psittaci ( C. psittaci) through bioinformatic prediction and experimental verification, and to characterize their subcellular localization in host cells. Methods:Potential effector proteins were predicted using bioinformatics tools. Candidate effectors were fused to β-lactamase through the constructed expression vectors, and these vectors were transformed into C. psittaci. The secretion of these candidate effectors was evaluated by β-lactamase translocation assays. Eukaryotic expression vectors of confirmed effectors were transfected into host cells to determine their intracellular localization patterns. Results:Bioinformatic analysis identified 29 candidate effector proteins. Experimental validation confirmed the secretion of five effectors, with four exhibiting cytoplasmic localization and one displaying nuclear localization in host cells.Conclusion:This study characterizes five novel C. psittaci secreted effector proteins, providing critical insights for investigating the molecular pathogenesis of psittacosis.

Objective:To analyze the incidence and perinatal factors of death or severe intraventricular hemorrhage (sIVH) within the first week of life in preterm infants with gestational age <32 weeks.Methods:Based on the online data platform of Sina-northern Neonatal Network, a case-control study was conducted using clinical data from 8 903 preterm infants with gestational age <32 weeks admitted to 35 neonatal intensive care unit (NICU) between 2019 and 2023. Infants were classified by gestational age at birth into very preterm infants and extremely preterm infants. Infants who died or developed sIVH within the first week of life were defined as the case group, while those who survived and did not develop sIVH were defined as the control group. The general information of the infants, maternal perinatal factors, the 5 th minute Apgar score, incidence of hypothermia or early-onset sepsis, and the first arterial blood pH value were compared between the case and control groups of very preterm infants and extremely preterm infants. The χ2 test and Wilcoxon rank-sum test were used for intergroup comparisons. A multivariable logistic regression model was used to analyze the factors for death or sIVH within the first week of life in very preterm and extremely preterm infants. Results:Among the 8 903 preterm infants with gestational age <32 weeks, 4 993 (56.1%) were male, with a gestational age at birth of 30.0 (28.4, 31.0) weeks. A total of 865 cases (9.7%) were death or sIVH within the first week of life. The case group took up 5.8% (426/7 316) and 27.7% (439/1 587) of very preterm infants and extremely preterm infants, respectively. Compared to the control group, the case group of very preterm and extremely preterm infants both had higher incidences of low gestational age, low birth weight, small for gestational age, the 5 th minute Apgar score ≤7, early-onset sepsis, hypothermia at admission, and first arterial blood pH <7.20 (all P<0.001). The proportion of mother′s full course antenatal corticosteroids use were both lower in both case group (both P<0.001). Multivariate Logistic regression analysis revealed several risk factors for death or sIVH within the first week of life in very preterm and extremely preterm infants, including: low gestational age ( OR=0.70 and 0.74, 95% CI 0.60-0.82 and 0.66-0.83, both P<0.001), low birth weight ( OR=0.99 and 0.99, 95% CI 0.99-1.00 and 0.99-1.00, both P<0.05), early-onset sepsis ( OR=1.82 and 2.20, 95% CI 1.42-2.34 and 1.74-2.79, both P<0.001), the 5 th minute Apgar score ≤7 ( OR=1.41 and 2.69, 95% CI 1.10-1.81 and 2.17-3.34, both P<0.01), hypothermia at admission ( OR=1.55 and 1.38,95% CI 1.17-2.07 and 1.08-1.76,both P<0.05) and the first arterial blood pH <7.20 ( OR=2.20 and 2.57, 95% CI 1.70-2.84 and 2.05-3.21, both P<0.001). Multiple births were an independent risk factor only for extremely preterm infants ( OR=1.32, 95% CI 1.02-1.71, P<0.05). Prenatal administration of a full course of antenatal corticosteroids was identified as a protective factor in very preterm and extremely preterm infants ( OR=0.74 and 0.62, 95% CI 0.58-0.95 and 0.51-0.76, both P<0.05). Conclusions:The incidence of death or sIVH within the first week of life remains high in preterm infants with gestational age <32 weeks. The smaller gestational age and lower birth weight, early-onset sepsis, birth asphyxia, hypothermia at admission, and a first arterial blood pH <7.20 were independent risk factors for death or sIVH within the first week of life in preterm infants with gestational age <32 weeks. A full course of antenatal corticosteroids significantly reduced the risk of these adverse outcomes.

Objective:To determine the incidence of acute focal bacterial nephritis (AFBN) in children with febrile urinary tract infections (UTI) and to identify associated risk factors.Methods:A retrospective cohort study included 181 children hospitalized with febrile UTI at Fujian Children′s Hospital from April 2021 to September 2023. Demographic data, clinical manifestations, and laboratory findings were collected. Patients were categorized into AFBN group and non-AFBN group based on AFBN diagnosis. The incidence of AFBN within this febrile UTI cohort was determined. The diagnostic value for pre-antibiotic blood white blood cell (WBC) count and C-reactive protein (CRP) level, along with post-treatment fever duration and pyuria duration for AFBN was evaluated using the area under curve (AUC) of the receiver operating characteristic (ROC).Results:The cohort comprised 181 children with febrile UTI (100 boys and 81 girls), age of 0.6 (0.3, 1.0) years. Eleven patients (6.1%) were diagnosed with AFBN. For predicting AFBN, the AUC was 0.71 (95% CI 0.55-0.85, P=0.026) for pre-antibiotic WBC count and 0.80 (95% CI 0.71-0.90, P=0.001) for pre-antibiotic CRP level, with optimal cutoff values of 16.0×10 9/L and 80.1 mg/L, respectively. For post-treatment parameters, the AUC was 0.79 (95% CI 0.69-0.92, P=0.001) for fever duration and 0.84 (95% CI 0.72-0.97, P<0.001) for pyuria duration, with optimal cutoff values of 1.9 d and 5.5 d, respectively. The combination of pre-antibiotic WBC count >16.0×10 9/L and CRP>80.1 mg/L yielded a sensitivity of 0.73 and a specificity of 0.86 for AFBN prediction. Similarly, the combination of post-treatment fever duration ≥2 d and pyuria duration >5 d demonstrated a sensitivity of 0.82 and specificity of 0.88. Conclusions:AFBN incidence was 6.1% in this cohort of children with febrile UTI. AFBN should be highly suspected in febrile UTI children presenting with either a pre-antibiotic WBC count >16.0×10 9/L and CRP >80.1 mg/L, or a post-treatment fever duration ≥2 d and pyuria duration >5 d.

BACKGROUND:The occurrence of neuronal axonal injury can result in neurological dysfunction,and the facilitation of axonal elongation is anticipated to play a pivotal role in the treatment of diseases affecting the nervous system.OBJECTIVE:To investigate whether ectomesenchymal stem cells-derived extracellular vesicles can promote neuronal axonal elongation.METHODS:(1)Ectomesenchymal stem cells were obtained from nasal mucosa using the tissue adherence method,and the specific markers of were identified through immunofluorescence.Ectomesenchymal stem cells-derived extracellular vesicles were acquired via ultracentrifugation and identified.(2)Ectomesenchymal stem cells-derived extracellular vesicles(0,0.5,1.0,1.5 mg/mL)were incubated with PC12 cells for 72 hours.The cytotoxicity and proliferation of ectomesenchymal stem cells-derived extracellular vesicles on PC12 cells were assessed using the CCK-8 assay.(3)Ectomesenchymal stem cells-derived extracellular vesicles(1.0 mg/mL)were incubated with PC12 cells or neurons for 72 hours.The changes in axon length were observed using microscopic analysis.The expression levels of axon-related markers β3-tubulin(early stage),growth associated protein 43(middle stage),and neurofilament 200(mature stage)were analyzed through real-time fluorescence quantitative PCR and Western blotting.These investigations aimed to explore the potential of ectomesenchymal stem cells-derived extracellular vesicles in promoting neurite elongation within PC12 cells or neurons.RESULTS AND CONCLUSION:(1)The majority of the acquired ectomesenchymal stem cells exhibited a spindle-shaped morphology,while a minority displayed irregular shapes,and demonstrated high expression levels of mesenchymal stem cell-specific markers Nestin,CD44,and Vimentin.The obtained ectomesenchymal stem cells-derived extracellular vesicles fulfilled the biological criteria for extracellular vesicles.(2)Within the detected protein concentration range of 0.5 to 1.5 mg/mL,the proliferation of PC12 cells was promoted by ectomesenchymal stem cells-derived extracellular vesicles,and this effect was further enhanced with increasing concentrations.(3)Ectomesenchymal stem cells-derived extracellular vesicles increased the length of axons in PC12 cells and neurons and the expression of axon-related markers β3-tubulin,growth associated protein 43,and neurofilament 200.Above findings suggest that ectomesenchymal stem cells-derived extracellular vesicles have the potential to enhance neuronal axonal elongation.

Objective:This study aims to investigate the feasibility and safety of implanting leadless pacemakers in the low septum and its impact on cardiac electrical synchronization.Methods:A total of 36 patients who received leadless pacemaker implantation at Fuwai Central China Cardiovascular Hospital from January 2021 to August 2023 were included in this study.According to implantation sites of leadless pacemakers,patients were divided into mid-septal group(n=16)and low-septal group(n=20).The clinical characteristics and cardiac electrical synchronization were compared between the two groups.Results:There were 21 male patients,mean age was(68±13)years old.There was no statistical difference in the type of brady-arrhythmia between the two groups(P=0.73).There were 61 implant attempts in these 36 patients,and there was no significant difference in the number of attempts,procedure time,and pacemaker parameters between the two groups,but the average procedure time tended to be shorter in the low-septal group([84±37]minutes vs.[105±35]minutes,P=0.09).In terms of electrical synchronization,there was no statistical difference in QRS duration between the low-septal group and the mid-septal group([162.0±21.1]ms vs.[174.0±14.8]ms,P=0.20).There were no vascular puncture complications,cardiac perforation,or pericardial tamponade during the procedure.There were no complications and readmissions related to the leadless pacemaker during follow-up period.Conclusions:Our results show that the implantation of a leadless pacemaker in the low ventricular septum is safe and effective,has a similar impact on cardiac electrical synchronization as mid-septal pacing.