ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

Objective To explore the clinical characteristics of organ donors in the intensive care unit (ICU), analyze the impact of comprehensive ICU treatment on organ function maintenance and donation efficiency, and provide data support for optimizing organ donation management strategies. Methods A retrospective analysis was conducted on the data of 263 donors who underwent organ donation after ineffective active treatment in the ICU of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2020 to January 2024. The clinical characteristics, main therapeutic measures in the ICU, and organ donation situations were analyzed. Results The 263 organ donors had an out-of-hospital hospitalization duration of 2 (1, 5) days and an in-hospital hospitalization duration of 4 (3, 6) d. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score at admission was (21±5). Among them, 16.7% had a history of cardiopulmonary resuscitation, 30.4% had a history of hypertension, and 48.7% had a history of cranial surgery. The duration of enteral nutrition provided in the ICU was 18 (8, 32) h, with daily energy provision of 160 (0, 320) kcal, parenteral nutrition provided non-protein energy of 877 (710, 1 058) kcal daily. Fiberoptic bronchoscopy was performed 0.25 (0, 0.50) times a day. Continuous renal replacement therapy (CRRT) was performed in 90.1% of the cases, with an average daily duration of 10 (6, 16) h. The daily dosage of human albumin was 40 (30, 50) g, and the daily dosage of methylprednisolone was 120 (80, 160) mg. The most commonly used empirical anti-infection regimens included cefoperazone-sulbactam in 59 cases (22.4%), meropenem combined with vancomycin in 31 cases (11.8%), and piperacillin-tazobactam in 29 cases (11.0%). The most commonly used goal-directed anti-infection adjustment regimen was meropenem combined with vancomycin in 21 cases (8.0%). After comprehensive treatment in the ICU, cardiac function, some liver functions, some coagulation functions, renal function, electrolytes, and infection indicators improved. A total of 981 organs were donated by the 263 organ donors, with 23 organs discarded. The average organ yield rate was 3.64, and the organ utilization rate was 97.7%. Conclusions Comprehensive ICU treatment may significantly improve the cardiac function, some liver functions, coagulation functions, and infection indicators of organ donors, enhance the effect of organ function maintenance, and provide an effective guarantee for optimizing organ donation management in the ICU and improving organ utilization rates.

Objective To investigate the situation and influencing factors of preserved ratio impaired spirometry (PRISm) among dust-exposed workers in a wooden furniture manufacturing enterprise. Methods A total of 562 dust-exposed workers from a wooden furniture enterprise in Guangdong Province were selected as the study subjects using the convenience sampling method. The result of health-status questionnaire and occupational medical examinations among the participants were studied, and the influencing factors of PRISm were studied using the binary logistic regression analysis method. Results The detection rate of PRISm was 22.1% (124/562) among the study subjects. Binary logistic regression result showed that male workers had a higher risk of PRISm than female workers (P<0.01). Current smokers had a higher risk of PRISm than non-smokers (P<0.05). Workers with longer duration of exposure to occupational hazards had a higher risk of PRISm (P<0.05), those with higher grade of small-airway dysfunction had a higher risk of PRISm (P<0.01). In terms of body mass index, overweight or obese workers showed a higher detection rate of PRISm than those with normal weight (P<0.01). Greater amount of smoking pack per year had a higher risk of PRISm (P<0.01). Conclusion Dust-exposed workers in the wooden furniture manufacturing industry show a relatively high detection rate of PRISm. Male, current smoker, longer duration of exposure to occupational hazards, small airway dysfunction, overweight or obese, and smoking pack per year are influencing factors of PRISm among the dust-exposed workers in the wooden furniture manufacturing industry.

Objective: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m 2 ) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this phase I trial, a time-to-event Bayesian optimal interval design was used.Docetaxel was given at a starting dose of 60 mg/m2 and was increased in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The doselimiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. Results: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m2 , no DLT was reported. DLTs were observed in one patient who received 70 mg/m2 docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m2 docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m2 in combination with cisplatin 75 mg/m2 had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. Conclusion Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be used safely at intraperitoneal doses of 75 mg/m2 in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac⁴C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac⁴C modification sites, thereby providing a potent sequencing tool for tRNA-ac⁴C research. Our findings expand the repertoire of tRNA ac⁴C modifications and identify a role of tRNA ac⁴C in the regulation of mRNA translation in HNSCC.
Humans ; DNA-Binding Proteins ; Head and Neck Neoplasms/genetics* ; N-Terminal Acetyltransferases ; RNA, Transfer ; Serine ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck

Objective To evaluate the effect of sodium hyaluronate combined with recombinant human epidermal growth factor(rhEGF)in the treatment of dry eye after cataract surgery.Methods Patients with dry eye after cataract surgery were divided into treatment group and control group.The control group was treated with sodium hyaluronate eye drops via dropping into the conjunctival sac,a drop per dose,tid,for 4 weeks.On this basis,the treatment group was treated with rhEGF eye drops via dropping into the conjunctival sac,1-2 drops per dose,tid,for 4 weeks.The two groups were compared on overall clinical efficacy,dry eye symptoms before treatment and after 4 weeks of treatment.Tear-film breakup time(BUT),basic tear secretion test(schirmer Ⅰ test,SⅠT),corneal fluorescein staining(CFS)score,meibomian gland yield secretion score(MGYSS),and the levels of tear inflammatory factors were compared between two groups before treatment and after 4 weeks of treatment.The safety was evaluated.Results Finally,41 cases and 39 cases were included in the treatment group and the control group,respectively.After treatment,the total effective rates in the treatment group and the control group were 95.12％and 79.49％,with statistically significant difference(P＜0.05).After 4 weeks of treatment,dry eye symptom scores of the treatment group and control group were 1.42±0.18 and 2.31±0.26;BUT were(11.89±1.26)and(10.46±1.27)s;SⅠT were(10.12±1.35)and(8.45±0.87)mm;CFS scores were 0.83±0.11 and 1.94±0.25;MGYSS scores were 10.85±1.17 and 12.43±1.56;interleukin-1β levels in tears were(35.26±3.53)and(74.12±7.55)ng·L-1;interleukin-6 levels were(8.35±0.86)and(12.41±12.56)pg·mL-1.Compared with the control group,the above indexes in the treatment group were statistically significant(all P＜0.05).The incidence rates of adverse drug reactions in the treatment group and the control group were 12.20％and 10.26％,without statistically significant difference between the groups(P＞0.05).Conclusion Sodium hyaluronate combined with rhEGF can significantly improve dry eye symptoms after cataract surgery,enhance the stability of tear film,reduce tear inflammatory factors,and protect the integrity of meibomian gland.

Personalized medicine emphasizes individualized and dynamic treatment decisions. There is an urgent need for a new efficacy evaluation system that can adapt to this approach. By reviewing past clinical research practices， this article pointed out the innovative needs of traditional Chinese medicine （TCM） efficacy evaluation from the perspective of personalized medicine in terms of ethical review， trial design， data management， and statistical analysis. Focusing on these needs， the article has proposed a strategic framework using syndrome differentiation and treatment in TCM as an example. The framework includes a method based on subgroup dynamic-static parallel group design and analysis， a safeguard mechanism of continuous review， dynamic informed consent， and multicenter ethical review， a technological support platform for personalized clinical efficacy evaluation and evidence support， and a statistical strategy integrating Bayesian and traditional analysis methods， aiming to promote the development of personalized TCM diagnosis and treatment.

Surface guided radiation therapy (SGRT) is a non-radiation, non-invasive technology that provides continuous postural monitoring of patients during radiotherapy. Using advanced 3D optical surface localization and tracking technology, SGRT quickly captures the surface contour information of patients through optical means to generate high-precision 3D surface contours, enabling real-time monitoring of patients during radiotherapy to ensure its accuracy. This image-guided technology has been widely applied in radiotherapy for tumors in different parts of the body, such as breast, intracranial, head and neck, and limbs. SGRT can reduce initial setup errors and provide real-time monitoring during treatment, or be combined with respiratory gating and deep inspiration breath-hold techniques. SGRT can also reduce radiation dose by reducing the use of CBCT, improve patient comfort with the use of immobilization devices, and enhance clinical speed, efficiency, and safety. This review aims to provide an overview of the commonly used technology and clinical applications of SGRT, and discuss its current limitations and future prospects.

Objective To investigate the effect of nobiletin on platelet-activating factor(PAF)metabolism in diabetic rats with renal injury.Methods Totally 72 rats were randomly divided into control group(n=10)and modeling group(n=62).The modeling group rats were induced to develop a diabetic rat model with renal injury and then further divided into the model group,aspirin group(20 mg/kg),and nobiletin low(50 mg/kg),medium(100 mg/kg),and high-dose(200 mg/kg)groups,each with 10 rats.After continuous oral administration for 6 weeks,rat body weight,kidney weight,and kidney index were measured.Histopathological assessments were conducted by using HE,periodic acid-Schiff staining(PAS),Masson staining,and transmission electron microscopy.Blood glucose levels,renal function,inflammatory factors,PAF and its regulatory factors were detected.Expression levels of PAF metabolism-related proteins,PAF-acetylhydrolase(PAFAH),PAF receptor(PAFR),and cholinephosphotransferase 1(CHPT1)in kidney tissues were assessed using Western blotting and immunohistochemistry.Results Following nobiletin intervention,rat body weight increased while kidney weight and kidney index decreased.Improvement in renal tissue pathology was observed,with reduced interstitial fibrosis and thinner basement membrane.Fasting blood glucose and glycated hemoglobin decreased,while fasting insulin showed no significant improvement.Urea nitrogen,blood creatinine,cystatin C,and 24-hour urinary protein excretion were reduced.Levels of interleukin(IL)-1α,IL-6,IL-8,and tumor necrosis factor(TNF-α)were lowered.PAF and its regulatory factors decreased.PAFR and CHPT1 expression decreased,while PAFAH increased.Conclusion Nobiletin can alleviate renal injury in diabetic rats with renal injury,improve kidney function,regulate blood glucose,and mitigate inflammatory response.Its mechanism may be associated with the modulation of platelet-activating factor metabolism.