OBJECTIVE To observe the effects of endogenous metabolite mesaconate combined with Sodium lactate Ringer’s injection （LR） on prolonging the golden treatment time window and its resuscitation efficacy in rats with hemorrhagic shock under high-altitude conditions. METHODS Rats were divided into the shock group， LR group， and 5， 20， 50 mg/kg mesaconate+LR groups， with 20 rats in each group， to investigate the effect of additional use of mesaconate on the golden treatment time window. After establishing a model of uncontrolled hemorrhagic shock under high-altitude conditions in all groups by housing in a hypobaric hypoxia chamber combined with splenic artery transection， rats in the shock group received no resuscitation， while rats in the LR group and mesaconate+LR groups underwent low-pressure resuscitation with LR or mesaconate combined with LR. Blood pressure control， fluid infusion volume， blood loss rate and survival status were observed in each group. Rats were further divided into the normal group， shock group and mesaconate （50 mg/kg）+LR group， with 10 or 20 rats in each group， to evaluate the resuscitation effects after extending the golden treatment time window by additionally using mesaconate. Except for the normal group， the other groups underwent the same procedure to establish an uncontrolled hemorrhagic shock model under high-altitude conditions. Rats in the shock group received no resuscitation. In the mesaconate+LR group， after 3 h of low-pressure resuscitation， bleeding control was performed by ligation of the spleen artery， and the infusion volume and blood loss rate were recorded； subsequently， the rats received LR resuscitation with twice the volume of blood loss. Then， blood gas indicators of the mesaconate+LR group were measured at different time points. Survival rates， indicators related to sublingual microcirculatory perfusion， liver and kidney blood flow， indicators related to the function of vital organs， and lung and brain water content were observed in all groups. RESULTS LR infusion alone could effectively maintain mean arterial pressure （MAP） within 50-60 mmHg for approximately 1 h. The administration of mesaconate combined with LR during hypotensive resuscitation could maintain MAP within 50-60 mmHg for over 3 h， with significantly reduced fluid infusion volume and blood loss rate in 50 mg/kg mesaconate+LR group， compared to the LR group （ P ＜0.05）. In the LR group， rats maintained low pressure for up to 1 hour with a survival rate of 52.94%， and no rats survived beyond 2 h. In the 5， 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 1 h with a survival rate exceeding 80%； in the 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 3 h with a survival rate exceeding 70%. After complete resuscitation with mesaconate combined with LR， the 72 h survival rate of rats was 43.75%， and significant improvements in blood gas parameters were observed compared to the end of the shock phase （ P ＜0.05）. Compared to the shock group， the mesaconate+LR group showed significant recovery in sublingual microcirculatory indicators， and liver/kidney blood flow after complete resuscitation （ P ＜0.05）， with significant reductions in heart， liver and kidney function-related indicators and lung water content （ P ＜0.05）. CONCLUSIONS Mesaconate combined with LR significantly extends the golden treatment time window for hemorrhagic shock in rats under high-altitude conditions， improves blood gas parameters， sublingual microcirculatory perfusion， and liver/kidney blood flow， mitigates vital organ impairment and pulmonary edema， and increases the survival rate of shocked rats.

Objective To systematically evaluate malnutrition risk factors in diabetic foot patients through systematic review and inform evidence-based nutritional interventions.Methods A top-down search of the literature on risk factors for malnutrition in patients with diabetic foot was conducted according to the"6S"pyramid model,using a computerized decision-making system,clinical guideline websites,professional association websites and databases,with a timeframe of up to March 2025 for the search.Totally 2 researchers independently performed literature screening,quality assessment,and data extraction.Meta-analysis was conducted using Stata 18 software.Results Totally 23 studies with a total sample size of 5 068 cases were included.There were 10 influencing factors being extracted,including age(OR=2.709),BMI(MD=0.709),duration of diabetes mellitus(OR=2.589),glyco-sylated hemoglobin(OR=2.190),albumin(MD=0.578),hemoglobin(OR=2.948),infection(OR=1.816),C-reactive protein(OR=2.228),Wagner classification of diabetic foot(OR=4.620)and degree of self-care(OR=0.220).The incidence of malnutrition in DFU patients who were assessed by the MNA-SF tool,the MNA tool and GLIM tool were 52.2％,70.2％and 41.4％.Conclusion The incidence of malnutrition in DFU patients is relatively high.Healthcare providers should continuously monitor the nutritional status of diabetic foot patients and implement personalized intervention plans to prevent malnutrition.

Objective: To summarize the laboratory findings of a case of hemolytic disease of the fetus and newborn (HDFN) caused by Rh system anti-c antibodies and to review the literature, so as to explore the characteristics of anti-c HDFN. Methods: The ABO blood type, Rh blood type, direct antiglobulin test (DAT) results, and the presence of unexpected antibodies and their titers were determined by serological methods. The cases of anti-c HDFN in our laboratory in China and abroad were statistically analyzed, and the incidence of severe HDFN caused by anti-c, anti-D and anti-E was compared. Results: The blood type of the child was B (Rh CcDee) with a positive DAT. Anti-c antibody was detected in both serum and eluate, with a serum antibody titer of 4. The mother’s blood type was AB (Rh CCDee) with a negative DAT, and anti-c antibody was detected in the serum with a titer of 128. Among 20 cases of anti-c HDFN, 17 were DAT positive, and 9 (45%, 9/20) underwent blood transfusion or exchange transfusion. The incidence of severe HDFN was 47.60% (10/21) for anti-c, 47.60% (10/21) for anti-D and 31.30% (5/16) for anti-E. Conclusion: Maternal pregnancy and/or blood transfusion are the main reasons for the production of Rh alloantibodies such as anti-c. The prevention and management of anti-c should be similar to that of anti-D. Rh antigen-matched (five antigens of Rh blood group) transfusion is necessary for women of childbearing age to avoid antibody production, and Rh typing and antibody screening during prenatal examination is recommended to ensure early detection, intervention and treatment.

Hilar cholangiocarcinoma is insidious in onset and often causes obstructive jaundice due to bile stasis,leading to impaired liver function.For tumors with malignant obstructive jaundice,biliary drainage is often performed before surgery in clinical practice.Currently,the commonly used drainage methods are percutaneous transhepatic biliary drainage(PTBD)and endoscopic retrograde biliary drain-age(ERBD),but there are controversies over the advantages and disadvantages of the two drainage methods.PTBD drainage can often lead to tumor implantation metastasis,but the underlying mechanism remains unclear.We detected tumor cells in PTBD and ERBD bile samples from hilar cholangiocarcino-ma patients,subsequently explored their tumorigenicity and mechanisms through tumorsphere assay in vitro and xenograft tumor models in vivo.The experiments included benign gallstones group(30 cases)as a negative control,PTBD group(14 cases)and ERBD group(13 cases).Tumorsphere formation was i-dentified in 3 cases(23％)among the 13 cases of ERBD group,in 6 cases(42％)among the 14 cases of PTBD group,but there were no tumor cells or formed tumorspheres in the 30 cases of benign gallstone group.The tumor sphere formation ability of cells in the PTBD group was significantly higher than that in ERBD group.Subcutaneous xenograft tumor assays showed that tumor growth in the PTBD group was sig-nificantly higher than that in the ERBD group.Tumor cells in PTBD bile possessed stronger tumorigenici-ty compared with the ERBD group.Mechanically,stem cell transcription factor Nanog mRNA levels were significantly higher in the PTBD group compared to the ERBD group.Both tumorsphere formation and xenograft tumor growth were reduced by Nanog knockdown in three cases of the PTBD group,indicating the important roles of Nanog in tumorigenicity of PTBD group tumor cells.The half-life of Nanog mRNA was longer in PTBD group cells than in ERBD group cells,suggesting potential post-transcriptional regu-lation on Nanog mRNA.The Nanog m6A level was higher in PTBD group tumor cells compared to the ERBD group.Analysis of methyltransferases and demethylases,ALKBH5(α-ketoglutarate dependent dioxygenase alkb family homolog 5)mRNA levels were lower in the PTBD group than in the ERBD group and significantly correlated with the m6A level of Nanog.ALKBH5 knockdown led to an increase in the m6A level of Nanog,while ALKBH5 overexpression decreased the m6A level of Nanog.Dual-luciferase activity assays demonstrated that ALKBH5 knockdown significantly enhanced luciferase activity,whereas ALKBH5 overexpression reduced it.Further studies confirmed that ALKBH5 knockdown upregulated both the mRNA and protein levels of Nanog,whereas overexpressing ALKBH5 downregulated them.ALKBH5 mediated the demethylation modification of Nanog mRNA,and the lower levels of ALKBH5 expression in the PTBD group promoted Nanog's m6A modification.Overexpressing ALKBH5 decreased tumorsphere growth,while ALKBH5 knockdown increased it,which was subsequently reduced by the simultaneous Nanog knockdown again.In sum,tumor cells in PTBD and ERBD drainage bile from hilar cholangiocar-cinoma patients exhibited tumorigenicity.Compared to the ERBD group,tumor cells in PTBD bile with lower ALKBH5 expression levels enhanced Nanog's m6A modification to upregulate Nanog expression levels,resulting in stronger tumorigenicity.These findings are significant for elucidating propensity to tumor implantation metastasis from PTBD drainage.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To explore whether creatine therapy regulates neuronal ferroptosis by inhibiting the activation of STAT1 signaling pathway associated with suppressor of cytokine signaling 1(SOCS1)in Alzheimer's disease.Methods Immunohistochemical staining and counting of positive results using paraffin sections of human brain frontal lobes were employed to determine the trend of changes in the target proteins.Further validation was performed by immunofluorescence and Western blotting.STAT1 phosphorylation was inhibited by creatine injection using eleven FAD4T mice and by cerebellar medullary pool puncture,and the expression of target proteins was examined by immunohistochemistry and immunofluorescence after postmortem sampling.Results Compared with the age controls,interferon-γ(IFN-γ),an activating cytokine of the STAT1 signaling pathway,and SOCS1,a negative regulator of STAT1 activation,were both significantly up-regulated,STAT1 phosphorylation was enhanced,and the ferroptosis markers ferritin light chain(FTL)and cystine/glutamate transporter(xCT)increased markedly in the cortex of AD human brains;Creatine treatment of FAD4T mice resulted in a reduction of both IFN-γ and SOCS1,and a significant decrease in the ferroptosis markers FTL and xCT(SLC7A11).Conclusion Creatine ameliorates neuronal ferroptosis in AD model mice by reducing neuronal STAT1-SOCS1 signalling activation.

Objective:To summarize preliminary experience and outcomes of transoral robotic surgery (TORS) in hypopharyngeal cancer.Methods:Clinical data of 28 patients with hypopharyngeal cancer underwent TORS with Da Vinci Si or Xi surgical system in three medical centers(Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University and Eye & ENT Hospital of Fudan University) in China from Sep 2017 to Mar 2024 were respectively analyzed. All patients were males, aged from 47 to 82(62.5±7.1) years old. According to TNM staging of AJCC, the stages included T1 in 6 cases, T2 in 17 cases, T3 in 3 cases and T4 in 2 cases; N0 in 18 cases, N1 in 3 cases, N2 in 6 cases, N3 in 1 case. SPSS version 26 was applied, and with Kaplan-Meier surviving curves, overall survival, local control rate and disease-free survival for those patients were calculated.Results:All 28 patients underwent successfully their TORS, no any case with transfer opening or positive surgical margin. Two patients died within one month after surgery. Two patients experienced minor oral bleeding, and subsenquently was cured. The follow-up period ranged from 1 to 81 months, with an average of 24.8 months, in which, five patients(17.9%) died, five patients(17.9%) experienced local recurrence and four patients(14.3%) had distant metastases. The three year overall survival, local control rate and disease-free survival were 77.1%, 74.6% and 57.1%, respectively.Conclusion:In properly selected cases of hypopharyngeal cancer, TORS can offer acceptable survival and local control rates, which can be considered as a new useful option for the surgery of hypopharyngeal cancer.

Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Objective To propose a dynamic electrical impedance tomography imaging algorithm based on complementary information fusion network(CIFN)to enhance image quality of dynamic electrical impedance imaging.Methods There were three modules for initialization,multi-frame complementary information extraction and information fusion involved in the CIFN.Firstly,multi-frame dynamic conductivity distribution images were obtained by the initialization module;secondly,spatial complementary information was extracted from the images by using the multi-frame complementary information extraction module;finally,the fusion of lesion target distribution information and target re-reconstruction were realized by the information fusion module to aquire high-quality EIT images.With a 16-electrode multilayer cranial simulation model,the CIFN-based imaging method was compared with Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm in terms of imaging results of types of lesions to verify its performance.Results Compared with the Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm,the proposed CIFN-based algorithm exhibited the lowest mean absolute error(MAE)and the highest structural similarity(SSIM)when used to image different lesion targets,which accurately reconstructed the distribution of lesion targets and gained high imaging stability under common noise levels.Conclusion The proposed CIFN-based imaging algorithm obtains high imaging quality on a cranial simulation model and reconstruction results close to the real model distribution,which provides algorithmic support for subsequent clinical studies on electrical impedance imaging.[Chinese Medical Equipment Journal,2025,46(6):1-6]