Onco-critical care has emerged as an important subspecialty at the intersection of critical care medicine and oncology, attracting increasing attention in recent years. With continuous innovations in cancer therapies, patient survival has improved significantly; however, the incidence of associated critical complications has also increased. The reasons for cancer patients requiring intensive care unit admission are diverse and can be broadly categorized into three groups: progression of the underlying malignancy, treatment-related complications, and coexisting classical critical illnesses. Traditional critical care concepts and practices face limitations in addressing the multidimensional and heterogeneous challenges of onco-critical care. Based on the core mechanism of critical illness development—host/organ unregulated response (HOUR)—this article systematically elaborates on how this framework advances understanding and clinical practice into onco-critical care, with emphasis on its manifestations in neuroendocrine, immune-inflammatory, and coagulation-metabolic pathways. The review summarizes recent advances in clinical assessment and phenotyping systems for onco-critical illness and discusses a multidisciplinary, integrated management strategy centered on the "Disease Control, Host Response Modulation, Organ Support" triad. Finally, major challenges and future directions in this field are outlined. By integrating existing evidence and theoretical insights, this review aims to provide new perspectives and a theoretical foundation for the clinical management of onco-critical illness, thereby promoting its evolution toward precision and standardization.

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective:To analyze the clinical characteristics and treatment outcomes of children with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody-mediated necrotizing myopathy, and to explore early identification and management strategies to provide reference for clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data and treatment outcomes of 10 pediatric patients with anti-HMGCR antibody-mediated necrotizing myopathy admitted to the Department of Rheumatology, Children′s Hospital of Fudan University from December 2020 to December 2024. Statistical description was performed using SPSS 22.0.Results:Among the 10 patients, the male-to-female ratio was 1:4, the age of onset was (7.2±4.0) years, and the disease duration at diagnosis was (22.2±19.6) months. None had a history of statin exposure. Six patients presented with muscle weakness, and4 were diagnosed due to asymptomatic elevation of creatine kinase (CK); 4 had dermatomyositis-like rashes. All patients showed significantly elevated CK levels [median 3 291(1 969, 8 776)U/L] and underwent muscle biopsy. Histopathological findings revealed myofiber degeneration, necrosis, and regeneration in all cases, with inflammatory infiltration in 9 cases, MHC-Ⅰ positivity in all, and C5b-9 positivity in 9 cases. The median follow-up duration was (15.7±6.3) months. At the last follow-up, muscle strength was normal or nearly normal, and the CK median value had decreased to 977.5 (211.0, 3 536.0) U/L.Conclusion:For patients with suspected idiopathic inflammatory myopathy and significantly elevated CK, muscle-specific antibody testing-including anti-HMGCR-and muscle biopsy should be performed promptly regardless of the presence of skin rash, to ensure accurate diagnosis and guide treatment, thereby avoiding misdiagnosis or missed diagnosis.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.

Purpose Discover new prostate cancer-related single nucleotide variants.Methods Tissue wax blocks from 21 prostate cancer patients who underwent radical surgery and had relatively complete clinical data were collected for somatic mutation detection to analyze new mutated genes associated with prostate cancer.The levels of cor-responding proteins in the urine of prostate cancer patients were tested according to the results of the selected genes.Results All 21 prostate cancer patients showed obvious somatic mutations,and the mutation types were dominated by C＞T and G＞A.The number of somatic mutations was 521,of which 27 genes had high mutation proportions(≥2 ca-ses),including ZSWIM6(5/21),FOXA1(4/21),SPTA1(2/21),FAM47C(2/21),FLG2(2/21),PRSS3(2/21),TP53(2/21),FLG(2/21),UBR4(2/21),and the mutations occurring in ZSWIM6 were all deletion muta-tions,and the mutations occurring in FOXA1 were missense mutations,deletion mutations,and deletion insertion mu-tations.The urinary levels of UPF1,SPTA1,and IDH1 proteins of the 10 prostate cancer patients were significantly different than those of the healthy controls.Correlation analysis showed that FOXA1 was positively correlated with UBR4(r=0.669,P=0.001),SPTA1 was positively correlated with FLG2(r=1.000,P＜0.001),FAM47C was positively correlated with PRSS3(r=1.000,P＜0.001),and there was a significant positive correlation between TP53 and FLG(r=1.000,P＜0.001).ZSWIM6 and FOXA1 were not correlated with biochemical recurrence.SP-TA1 mutation affected progression-free survival(PFS)[(66.0±0)months vs(30.0±7.8)months,P=0.008].FAM47C was positively correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].ZNF676 was correlated with PFS[(66.0±0)months vs(26.0±5.0)months,P=0.008].FLG2 was correlated with PFS[(66.0±0)months vs(30.0±7.8)months,P=0.008].PRSS3 was correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].Conclusion All 21 prostate cancer patients harbored somatic mutations,including ZSWIM6(5/21)and FOXA1(4/21)mutations.SPTA1,FAM47C,ZNF676,FLG2,and PRSS3 may be associated with prognosis.

Objective:To observe any impact of supplementing conventional rehabilitation training with electrothermal acupuncture on the upper limb motor functioning of hemiplegic stroke survivors.Methods:Thirty-six hemiplegic persons who had recently survived a stroke were divided at random into an electrothermal acupuncture group ( n=18) and a control group ( n=18). Both groups received conventional rehabilitation training, while the electrothermal acupuncture group was additionally provided with daily 30-minute sessions of electrothermal acupuncture, 6 days per week for 3 weeks. Before and after the treatment everyone′s upper limb motor functioning was quantified using the Fugl-Meyer assessment (FMA-UE), and their ability in the activities of daily living (ADL) was assessed using the modified Barthel index (MBI). The Hong Kong version of the functional test for the hemiplegic upper extremity (FTHUE-HK) was also administered. Surface electromyography (sEMG) was employed to compute the co-contraction ratios (CRs) of the agonist to antagonist muscles during elbow flexion and extension. Results:After the treatment, both groups exhibited significant improvements in their average FMA-UE, FTHUE-HK and MBI results, but with significantly greater improvement in the electrothermal acupuncture group. The root mean square values of the wrist flexor and extensor and elbow flexor muscles during flexion showed significant improvement in both groups, with the average values in the electrothermal acupuncture group significantly better than those of the control group. The CR values during elbow extension in the electrothermal acupuncture group demonstrated significant improvement compared to before the treatment.Conclusions:Supplementing conventional rehabilitation measures with electrothermal acupuncture can better increase the strength of the elbow and wrist extensor muscles in the early days after a stroke. It promotes the recruitment of muscle fibers in the extensor muscle group, reduces abnormal coordination patterns in the elbow joint, and improves upper limb motor function, the practicality of hand function, and ability in the activities of daily living.

BACKGROUND:For patients with anterior cruciate ligament re-rupture after reconstruction with abnormally increased posterior slope of the tibial plateau,anterior cruciate ligament reconstruction combined with anterior closing-wedge high tibial osteotomy was performed.However,there is a lack of precise tools for osteotomy.OBJECTIVE:To investigate the effectiveness of three-dimensional(3D)printed accurate osteotomy template in anterior cruciate ligament revision for patients with excessive posterior slope.METHODS:The medical records of 30 patients who underwent anterior cruciate ligament revision combined with anterior closing-wedge high tibial osteotomy were retrospectively collected and divided into two groups according to the operation method.The trial group(n=15)was assisted by 3D printing osteotomy guide plate.The control group(n=15)was conventional surgery.The osteotomy time,fluoroscopy times,intraoperative and 24 hours postoperative blood loss,preoperative and 3 months postoperative tibiofemoral anatomical angle,medial proximal tibial anatomical angle,posterior slope,the difference between planned posterior slope correction angle and actual correction angle,and KT-2000 side-to-side difference before operation,3 and 24 months after operation were compared between the two groups.Lachman test and Pivot shift test were performed before operation,immediately after operation,and 24 months after operation.International Knee Documentation Committee score and Lysholm score were performed before operation,3 and 24 months after operation.RESULTS AND CONCLUSION:(1)The osteotomy time,fluoroscopy times,and blood loss during operation and 24 hours after operation in the trial group were significantly less than those in the control group(P＜0.05).(2)The posterior slope of the two groups decreased significantly after operation.There was no significant change in tibiofemoral anatomical angle and medial proximal tibial anatomical angle after operation.The difference between preoperative planned and postoperative actual posterior slope degree in the trial group(0.64±0.41)° was smaller than that in the control group(2.18±0.54)°,and the difference was statistically significant(P＜0.001).(3)The KT-2000 side-to-side difference was significantly reduced in both groups after surgery(P＜0.05).At 3 and 24 months after operation,there was no significant difference in KT-2000 side-to-side difference between the two groups(P＞0.05).The Lachman test and Pivot shift test of the two groups were negative immediately after operation,3 and 24 months after operation.(4)The International Knee Documentation Committee and Lysholm scores of the two groups increased significantly after surgery(P＜0.05).At 3 months after operation,the International Knee Documentation Committee score and Lysholm score of the trial group were significantly higher than those of the control group(P＜0.05).At 24 months after operation,there was no significant difference in International Knee Documentation Committee score and Lysholm score between the two groups(P＞0.05).(5)In conclusion,with the assistance of 3D printing accurate osteotomy guide plate,anterior cruciate ligament reconstruction combined with anterior closing-wedge high tibial osteotomy is easier to operate,with shorter operation time,fewer fluoroscopy times,less intraoperative and postoperative blood loss,and faster recovery of knee joint function after operation,which has high clinical application value.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.