ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.

Objective: To explore the independent risk factors of allogeneic blood transfusion during perioperative period of cytoreductive surgery in patients with ovarian cancer, and to construct a predictive model to facilitate clinical risk assessment and optimize perioperative blood management. Methods: Clinical data of 156 patients who underwent cytoreductive surgery for ovarian cancer in our hospital from January 2020 to December 2025 were retrospectively collected. The patients were divided into transfusion group (n=51) and non-transfusion group (n=105) according to whether they received allogeneic blood transfusion during perioperative period. The 1∶1 propensity score matching (PSM) was used to correct the confounding factors. Independent sample t test or Mann-Whitney U test was used for measurement data, and chisquare test was used for enumeration data. Variables with P<0.05 in univariate analysis were included in binary logistic regression for multivariate analysis to determine independent risk factors. A nomogram model for perioperative allogeneic blood transfusion risk prediction was constructed based on independent risk factors. Bootstrap method (100 samples) was used for internal calibration verification. ROC curve was used to evaluate the discrimination efficiency, and decision curve analysis (DCA) was used to evaluate the clinical net benefit of the model. Results: After propensity matching, the baseline data of the two groups were balanced and comparable. Multivariate logistic regression analysis showed that preoperative prothrombin time (PT) (OR=2.666, 95%CI 1.249~5.693, P=0.011), preoperative hemoglobin (Hb) (OR=0.953, 95%CI 0.923~0.984, P=0.003), intraoperative blood loss (OR=1.004, 95%CI 1.001-1.006, P=0.004), preoperative anemia grade (OR=3.052, 95%CI 1.007-9.252, P=0.049) were independent influencing factors of perioperative allogeneic blood transfusion. The nomogram model based on the above four factors was significant (LR χ =58.617, P<0.001), and the internal calibration curve showed that the predicted probability of the model was in good agreement with the actual probability (mean absolute error=0.042). The area under the ROC curve (AUC) was 0.890, indicating good discrimination efficiency. DCA showed that the clinical net benefit of the model was better than that of the unified transfusion/non-transfusion strategy in the 0-0.45 risk threshold range. Conclusion: Intraoperative blood loss, preoperative PT, preoperative Hb and preoperative anemia grade are independent risk factors for perioperative allogeneic blood transfusion in patients undergoing cytoreductive surgery for ovarian cancer. The nomogram model based on the above factors has good predictive efficacy and clinical hierarchical decision-making value, which can provide reference for clinical implementation of individualized blood management for high-risk patients and reduction of unnecessary blood transfusion rate.

BACKGROUND:Streptococcus mutans is an important pathogen of dental caries,and timely detection of its levels is of great significance for early detection and treatment of dental caries. OBJECTIVE:To evaluate the effect of loop-mediated isothermal amplification(FTA-LAMP)direct extraction of Streptococcus mutans DNA. METHODS:(1)Bacterial suspensions containing ATCC standard strains(Streptococcus mutans)were prepared and inoculated into the brain-heart leachate medium.After mixed thoroughly,the mixture was then diluted in a 10-fold gradient into seven concentrations(4.2×107,4.2×106,4.2×105,4.2×104,4.2×103,4.2×102,4.2×10 CFU/mL),two parallel controls were made for each dilution level,and sterile water was used as a blank control.(2)The DNA of Streptococcus mutans was extracted using FTA Elute card,boiling method,kit extraction and lysate extraction methods separately and then amplified using LAMP technology was amplified.A specificity test was also performed to compare the differences between the four DNA extraction methods.RESULTS AND CONCLUSION:The DNA extracted by all four methods met the requirements for LAMP amplification.Specificity test results showed that only Streptococcus mutans could specifically amplify the target gene.The detection limit value of the DNA concentration was 4.2×103 CFU/mL for the lysate method,4.2×104 CFU/mL for the FTA Elute card extraction method,4.2×106 CFU/mL for the kit extraction method,and 4.2×107 CFU/mL for the boiling method.In the other aspects of the four extraction methods,the kit extraction method had the highest experimental cost,number of steps and time;the other three methods had the same number of steps,with the FTA Elute card method requiring the least amount of instruments,the boiling method having the lowest single cost,and the lysate extraction method taking the least amount of time.Only a small amount of bacteria were needed for successful extraction using both the FTA Elute card and lysate extraction methods.Compared with the FTA Elute card method,the lysate extraction method was superior in terms of time,but it had a high single cost and required more equipment.To conclude,the FTA-LAMP technology established in this study has the advantages of ease of operation,high specificity,high sensitivity,and visualization,which is expected to be a new way for efficient extraction and detection of Streptococcus mutans.

Objective To analyze the external radiation dose rate and radiation protection measures during treatment of a patient with hepatocellular carcinoma (HCC) who underwent ⁹⁰Y selective internal radiotherapy (⁹⁰Y-SIRT). Methods A male HCC patient who received ⁹⁰Y-SIRT with an activity of 4.65×10⁹ Bq was selected as the research subject using retrospective analysis. External radiation dose rate meters were used to detect ambient dose equivalent rates around the radiation worker, the HCC patient, and the workplace during treatment. Surface contamination meters were used to detect surface contamination levels of the radiation worker and the workplace. Results The ambient dose equivalent rate around the interventional radiology staff during treatment ranged from 3.7 to 39.0 μSv/h. The patient's ambient dose equivalent rate of surgical site at distances of 30, 100, and 200 cm ranged from 45.0 to 5.6, 4.4 to 0.4, and 0.4 to 0.1 μSv/h respectively without protection, and 14.0 to 3.4, 3.2 to 0.3, and 0.4 to 0.1 μSv/h respectively when the surgical site was covered with a 1.0 mmPb lead rubber drape after 0.0 to 161.0 hours of the surgery. In the nuclear medicine department, ambient dose equivalent rate of the workplace ranged from 0.4 to 740.0 μSv/h. The ambient dose equivalent rate around all monitoring points in the digital subtraction angiography operating room accounted at 0.1 μSv/h, and the observation ward ranged from 0.1 to 0.2 μSv/h. The β surface contamination levels of the radiation worker and workplace were below the minimum detection limit (0.16 Bq/cm²). Conclusion Radiation doses for both HCC patients and radiation worker remained within acceptable limits when appropriate protective equipment was used. A well-designed workplace layout is essential to ensure effective implementation of radiation protection.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

OBJECTIVES: To explore the molecular mechanism of Jiangzhi Huaban Decoction (JZHBD) for improving atherosclerosis through the "qi meridian-blood channels" pathway. METHODS: ApoE^-/- mouse models of atherosclerosis were established by high-fat diet feeding for 8 weeks, with C57BL/6 mice on a normal diet as the controls. Forty ApoE^-/- mouse models were randomized into model group, low-, medium-, and high-dose JZHBD treatment groups, and atorvastatin treatment group (n=8) for their respective treatments for 8 weeks. The changes in body weight and overall condition of the mice were monitored weekly. After the treatments, serum levels of TC, TG, HDL-C, LDL-C, TBA, ALT, and AST of the mice were measured, pathological changes in the liver and aortic root plaques were examined with HE staining, and lipid accumulation in the liver and aortic wall was assessed using Oil Red O staining. The core molecular mechanism was studied through transcriptomics, and the expressions of the key pathway proteins were confirmed using Western blotting and immunohistochemistry. RESULTS: Treatment with JZHBD significantly reduced blood lipid and total bile acid levels, improved liver function and hepatic steatosis, and decreased aortic lipid deposition and plaque area in the mouse models of atherosclerosis. Transcriptomic analysis suggested that the therapeutic mechanism of JZHBD involved reverse cholesterol transport, PPAR signaling, and the inflammatory pathways. In atherosclerotic mice, JZHBD treatment obviously up-regulated hepatic expressions of PPARγ, LXRα, ABCA1, ABCG1, and CYP7A1, down-regulated hepatic expressions of p-p65/p65, IL-6, IL1β in the liver, increased ABCG5 and ABCG8 expressions in the intestines, and decreased ICAM-1 and VCAM-1 expressions in the aortic plaques. CONCLUSIONS JZHBD improves atherosclerotic vascular damage and plaque formation possibly by regulating hepatic reverse cholesterol transport and inflammation via modulating the hepatic PPARγ/LXRα/NF-κB signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Plaque, Atherosclerotic/metabolism* ; Liver/metabolism* ; Mice ; Atherosclerosis/metabolism* ; Cholesterol/metabolism* ; PPAR gamma/metabolism* ; Male ; Diet, High-Fat ; Biological Transport

Objective To evaluate the safety and feasibility of remote robot-assisted thoracoscopic surgery utilizing 5G technology. Methods Clinical data from five patients who underwent 5G remote robot-assisted thoracoscopic surgery at the Thoracic Surgery Center of Gansu Provincial People's Hospital from May to October 2024 were retrospectively analyzed. Results Finally, five patients were included. There were 2 males and 3 females at median age of 50 (42-63) years. All five surgeries (including 1 patient of lobectomy, 3 patients of partial lung resection and 1 patient of mediastinal lesion resection) were successfully completed without conversion to thoracotomy, complications, or mortality. The median intraoperative signal delay across the patients was 39 (37-42) ms. The median psychological load score for the surgeons was 9 (3-13). The median operation time was 100 (80-122) minutes with a median intraoperative blood loss of 100 (30-200) mL. Catheter drainage lasted a median of 4 (3-5) days, and the median drainage volumes on the first, second, and third postoperative day were 200 (100-300) mL, 150 (60-220) mL, and 80 (30-180) mL, respectively. The median postoperative hospital stay was 4 (3-7) days, and the median pain scores on the third postoperative day were 3 (1-4), 3 (0-3), and 1 (0-3), respectively. Conclusion 5G remote robot-assisted thoracoscopic surgery is safe and effective, with good surgical experience, smooth operation and small intraoperative delay.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Objective:To explore the relationship between serum thymic stromal lymphopoietin (TSLP) levels and the occurrence of pruritus as well as interstitial lung diseases (ILD) in patients with dermatomyositis (DM) or clinically amyopathic dermatomyositis (CADM) .Methods:A retrospective analysis was conducted on the clinical data from 61 diagnosed DM/CADM patients at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between February 2019 and March 2022. Thirty-five age- and sex-matched healthy individuals were included as controls. Serum TSLP and anti-melanoma differentiation-associated gene 5 (MDA5) antibody levels were measured using enzyme-linked immunosorbent assay (ELISA) . A multiplexed flow cytometry assay was performed to detect the serum levels of 12 cytokines, including interferon (IFN) -α2, IFN-γ, interleukin (IL) -4, IL-5, etc. Pruritus severity in DM/CADM patients was assessed using the visual analog scale (VAS) . Relationships of serum TSLP levels with skin lesions, inflammatory markers, and the severity of ILD were analyzed using GraphPad Prism 8.0.1 and R (version 4.3.2) software.Results:Among the 61 patients with DM/CADM, 18 were males (13 with DM and 5 with CADM) and 43 were females (30 with DM and 13 with CADM) , with ages of 53.08 ± 14.97 years and disease duration of 6.27 ± 4.27 months. No significant differences were observed in sex or age between the DM/CADM group and the healthy control group (both P > 0.05) . Of the 61 patients, 15 (24.59%) were positive for anti-MDA5 antibodies, and 31 (51.67%) had ILD, including 11 with acute/subacute interstitial pneumonia (A/SIP) . The pruritus VAS score ( M[ Q1, Q3]) among the 61 patients was 3 (0, 6) points; 20 patients (32.79%) reported no pruritus, while 11 (18.32%) , 17 (27.87%) , and 13 (21.31%) experienced mild, moderate, and severe pruritus, respectively. Serum TSLP levels were significantly higher in the DM/CADM patients than in the healthy controls (91.0 [34.6, 273.0] vs. 25.0 [0.0, 83.5] pg/ml, Z = 1 502.50, P < 0.001]. The TSLP levels were significantly positively correlated with serum levels of alanine aminotransferase (ALT) , lactate dehydrogenase, C-reactive protein, erythrocyte sedimentation rate and ferritin, and significantly negatively correlated with pruritus VAS scores, eosinophil percentages, and eosinophil counts (all P < 0.05) . Serum TSLP levels were significantly higher in the anti-MDA5 antibody-positive patients than in the anti-MDA5 antibody-negative patients (273.0 [103.8, 2 576.0] pg/ml vs. 67.4 [16.9, 218.7] pg/ml, P = 0.002) , as well as in the patients with A/SIP than in those without A/SIP (390.0 [168.2, 2 869.6] vs. 67.5 [21.8, 235.9] pg/ml, P < 0.001) . ROC analysis showed that the combined detection of serum TSLP levels and anti-MDA5 antibodies had a higher predictive value for A/SIP in DM/CADM patients (AUC = 0.922) than either the detection of anti-MDA5 antibodies (AUC = 0.831) or TSLP (AUC = 0.824) alone did. Conclusions:Serum TSLP levels were significantly higher in patients with DM/CADM than in healthy controls, with particularly higher levels observed in anti-MDA5 antibody-positive patients and patients with coexisting A/SIP, and were correlated with several indicators of disease activity. The combination of serum TSLP levels and anti-MDA5 antibodies provided greater predictive value for A/SIP than either of them alone did.