OBJECTIVE: To investigate the predictive value of oxygenation index (PaO₂/FiO₂) at intensive care unit (ICU) admission on 30-day mortality in patients with sepsis. METHODS: A retrospective study was conducted. Patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to October 2023 were enrolled. The demographic information, comorbidities, sites of infection, vital signs and laboratory test indicators at the time of admission to the ICU, disease severity scores within 24 hours of admission to the ICU, treatment process and prognostic indicators were collected. According to the PaO₂/FiO₂ at ICU admission, patients were divided into Q1 group (PaO₂/FiO₂ of 4.1-16.4 cmHg, 1 cmHg ≈ 1.33 kPa), Q2 group (PaO₂/FiO₂ of 16.5-22.6 cmHg), Q3 group (PaO₂/FiO₂ of 22.7-32.9 cmHg), and Q4 group (PaO₂/FiO₂ of 33.0-94.8 cmHg). Differences in the indicators across the four groups were compared. Multifactorial Cox regression analysis was used to assess the relationship between PaO₂/FiO₂ and 30-day mortality of patients with sepsis. The predictive value of PaO₂/FiO₂, sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) on 30-day prognosis of patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 1 711 patients with sepsis were enrolled, including 428 patients in Q1 group, 424 patients in Q2 group, 425 patients in Q3 group, and 434 patients in Q4 group. 622 patients died at 30-day, the overall 30-day mortality was 36.35%. There were statistically significant differences in age, body mass index (BMI), history of smoking, history of alcohol consumption, admission heart rate, respiratory rate, APACHE II score, SOFA score, Glasgow coma score (GCS), site of infection, Combined chronic obstructive pulmonary disease (COPD), blood lactic acid (Lac), prothrombin time (PT), albumin (Alb), total bilirubin (TBil), pH, proportion of mechanical ventilation, duration of mechanical ventilation, proportion of vasoactive medication used, and maximal concentration, length of ICU stay, hospital stay, incidence of acute kidney injury, in-hospital mortality, 30-day mortality among the four groups. Multivariate Cox regression analysis showed that after adjusting for confounding factors, for every 1 cmHg increase in PaO₂/FiO₂ at ICU admission, the 30-day mortality risk decreased by 2% [hazard ratio (HR) = 0.98, 95% confidence interval (95%CI) was 0.98-0.99, P < 0.001]. The 30-day mortality risk in the Q4 group was reduced compared with the Q1 group by 41% (HR = 0.59, 95%CI was 0.46-0.76, P < 0.001). The fitted curve showed that a curvilinear relationship between PaO₂/FiO₂ and 30-day mortality after adjustment for confounders. In the inflection point analysis, for every 1 cmHg increase in PaO₂/FiO₂ at PaO₂/FiO₂ < 28.55 cmHg, the risk of 30-day death in sepsis patients was reduced by 5% (HR = 0.95, 95%CI was 0.94-0.97, P < 0.001); when PaO₂/FiO₂ ≥ 28.55 cmHg, there was no statistically significant association between PaO2/FiO2 and the increase in the risk of 30-day death in sepsis (HR = 1.01, 95%CI was 0.99-1.02, P = 0.512). ROC curve analysis showed that the area under the curve (AUC) for the prediction of 30-day mortality by admission PaO₂/FiO₂ in ICU sepsis patients was 0.650, which was lower than the predictive ability of the SOFA score (AUC = 0.698) and APACHE II score (AUC = 0.723). CONCLUSION In patients with sepsis, PaO₂/FiO₂ at ICU admission is strongly associated with 30-day mortality risk, alerting healthcare professionals to pay attention to patients with low PaO₂/FiO₂ for timely interventions.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Retrospective Studies ; Prognosis ; Hospital Mortality ; Oxygen ; Male ; Predictive Value of Tests ; Female ; Middle Aged ; Aged

Malignant tumors represent a major global public health challenge,necessitating urgent innovation in diagnostic and therapeutic strategies.Lactate,a key metabolic product of tumor cell glycolysis,functions not merely as an energy metabolite but also as a signaling molecule to regulate malignant progression.Lactate mediates intercellular metabolite distribution through monocarboxylate transporter(MCT)-driven lactate shuttling and regulates epigenetics via histone lactylation.This integration establishes interconnected networks of energy,amino acid,and lipid metabolism that enhance tumor metabolic plasticity.In immune regulation,lactate induces a shift of T cells toward immunosuppressive phenotypes,impedes CD8+T cell memory differentiation,and attenuates cytotoxicity.Simultaneously,lactate not only reduces the immune efficacy of natural killer(NK)cells but also triggers apoptosis by inducing mitochondrial dysfunction,creating an immune-privileged niche for metastatic sites.Furthermore,elevated lactate levels activate multiple signaling pathways to recruit macrophages and drive their polarization toward the M2 phenotype,fostering an immunosuppressive microenvironment.Current therapeutic strategies target key aspects of lactate metabolism.Inhibiting lactate synthesis reduces lactate accumulation in tumor microenvironment(TME),countering the tumor's metabolic advantage and diminishing its role in driving metabolic reprogramming.Additionally,promoting the decomposition of lactate represents a promising new direction.Novel agents employing bioenzymes or biomimetic catalytic systems enhance local lactate clearance,alleviating the immunosuppressive effects of the acidic TME.This review comprehensively outlined the lactate-mediated regulatory network,aiming to provide systematic research directions and translational insights for developing more effective anti-tumor therapies.

Objective To evaluate the short-term outcomes of robot-assisted partial nephrectomy(RAPN)in the treatment of renal cell carcinoma(RCC)involving segmental renal vein invasion,and to summarize relevant diagnostic experience and surgical techniques.Methods A retrospective analysis was conducted on the clinicopathological data of 23 RCC patients who were found to have segmental renal vein invasion during RAPN at Sun Yat-sen University Cancer Center during 2022 and 2024.All procedures were performed by the same experienced urologic surgeon(＞1000 robotic cases).Preoperative computed tomography(CT)scans of all patients failed to reveal segmental renal vein invasion.Two experienced radiologists re-evaluated the imaging postoperatively.The clinical and pathological data of patients were analyzed to preliminarily explore the short-term efficacy,imaging,intraoperative findings and pathological characteristics.Results All surgeries were completed successfully via the transperitoneal approach with renal preservation.The median operation time was 151.0(125.5,182.0)min,and median blood loss was 180.0(100.0,300.0)mL;2 patients(8.7％)required intraoperative transfusion;3(13.0％)experienced postoperative complications,all of which were minor(Clavien-Dindo grade 1-2).Postoperative pathology confirmed venous invasion in 2 patients.The diagnostic rates of segmental renal vein invasion by the two radiologists were 47.8％(11/23)and 21.7％(5/23),respectively,with concordance in only 3 cases.During a mean follow-up of 9.1 months,1 patient developed iliac lymph node metastasis without local recurrence 12.4 months after surgery.After reoperation to remove the metastatic focus,the patient was treated with Axitinib combined with Toripalimab and has survived to date.The remaining patients were followed up for an average of 8.9 months,with no recurrence or metastasis observed.Conclusion Preoperative detection of segmental renal vein invasion in RCC is challenging,and pathological confirmation is often inconsistent with intraoperative findings.For RCC patients with intraoperatively identified segmental renal vein invasion,RAPN performed by experienced surgeons is feasible and safe on the premise of ensuring complete tumor resection,with favorable short-term oncologic outcomes.Long-term results require further follow-up.

Objective:To illustrate the clinical modeling and commissioning results of Monte Carlo dose calculation algorithm in RayStation treatment planning system (TPS) for a domestically developed synchrotron-based spot scanning proton therapy system (SAPT-PS-01).Methods:The proton pencil beam model in RayStation required integral depth dose curves, spot profiles and absolute dose as the input beam data. It was not necessary to collect beam parameters with range shifter. The integral depth dose curves of a single spot were measured by an 8 cm parallel ion chamber. A 2-dimensional scintillation detector was used to measure the in-air spot profile at 5 different depths including the isocenter plane. The absolute dose was calibrated by a 0.25 cm parallel ion chamber under the single energy layer irradiation with a field size of 10 cm × 10 cm. After modeling, the results of the beam model and the Monte Carlo dose calculation algorithm were validated from the range, spot profile, point-dose in a spread-out Bragg peak, planar dose in a clinical plan, point dose in an end-to-end test.Results:For the 94 energy layers, the maximum deviation between the calculated and measured range was 0.03 cm. The maximum difference between the calculated and measured in-air spot sigma was 0.015 cm, and the deviation of in-water spot sigma was measured within ±15%. Compared with the measured values, the calculated dose deviation of 138 measured points in the spread-out Bragg peak was within 3%. For the planar dose verification of clinical plans, the TPS-calculated dose distribution of 285 planes agreed well with the measurement with a minimum gamma-passing rate of 90%, and the gamma passing rate of almost 95% of planes were greater than 95%. The point dose measurements for 8 beams in the end-to-end tests under 4 clinical scenarios were within 5%.Conclusions:The acceptable beam model validation results and successful end-to-end test confirm that the Monte Carlo dose calculation algorithm modeling for the synchrotron-based spot scanning proton therapy system is accurate, which is applicable for the design of patient treatment plan.

Objective To evaluate the short-term outcomes of robot-assisted partial nephrectomy(RAPN)in the treatment of renal cell carcinoma(RCC)involving segmental renal vein invasion,and to summarize relevant diagnostic experience and surgical techniques.Methods A retrospective analysis was conducted on the clinicopathological data of 23 RCC patients who were found to have segmental renal vein invasion during RAPN at Sun Yat-sen University Cancer Center during 2022 and 2024.All procedures were performed by the same experienced urologic surgeon(＞1000 robotic cases).Preoperative computed tomography(CT)scans of all patients failed to reveal segmental renal vein invasion.Two experienced radiologists re-evaluated the imaging postoperatively.The clinical and pathological data of patients were analyzed to preliminarily explore the short-term efficacy,imaging,intraoperative findings and pathological characteristics.Results All surgeries were completed successfully via the transperitoneal approach with renal preservation.The median operation time was 151.0(125.5,182.0)min,and median blood loss was 180.0(100.0,300.0)mL;2 patients(8.7％)required intraoperative transfusion;3(13.0％)experienced postoperative complications,all of which were minor(Clavien-Dindo grade 1-2).Postoperative pathology confirmed venous invasion in 2 patients.The diagnostic rates of segmental renal vein invasion by the two radiologists were 47.8％(11/23)and 21.7％(5/23),respectively,with concordance in only 3 cases.During a mean follow-up of 9.1 months,1 patient developed iliac lymph node metastasis without local recurrence 12.4 months after surgery.After reoperation to remove the metastatic focus,the patient was treated with Axitinib combined with Toripalimab and has survived to date.The remaining patients were followed up for an average of 8.9 months,with no recurrence or metastasis observed.Conclusion Preoperative detection of segmental renal vein invasion in RCC is challenging,and pathological confirmation is often inconsistent with intraoperative findings.For RCC patients with intraoperatively identified segmental renal vein invasion,RAPN performed by experienced surgeons is feasible and safe on the premise of ensuring complete tumor resection,with favorable short-term oncologic outcomes.Long-term results require further follow-up.

Malignant tumors represent a major global public health challenge,necessitating urgent innovation in diagnostic and therapeutic strategies.Lactate,a key metabolic product of tumor cell glycolysis,functions not merely as an energy metabolite but also as a signaling molecule to regulate malignant progression.Lactate mediates intercellular metabolite distribution through monocarboxylate transporter(MCT)-driven lactate shuttling and regulates epigenetics via histone lactylation.This integration establishes interconnected networks of energy,amino acid,and lipid metabolism that enhance tumor metabolic plasticity.In immune regulation,lactate induces a shift of T cells toward immunosuppressive phenotypes,impedes CD8+T cell memory differentiation,and attenuates cytotoxicity.Simultaneously,lactate not only reduces the immune efficacy of natural killer(NK)cells but also triggers apoptosis by inducing mitochondrial dysfunction,creating an immune-privileged niche for metastatic sites.Furthermore,elevated lactate levels activate multiple signaling pathways to recruit macrophages and drive their polarization toward the M2 phenotype,fostering an immunosuppressive microenvironment.Current therapeutic strategies target key aspects of lactate metabolism.Inhibiting lactate synthesis reduces lactate accumulation in tumor microenvironment(TME),countering the tumor's metabolic advantage and diminishing its role in driving metabolic reprogramming.Additionally,promoting the decomposition of lactate represents a promising new direction.Novel agents employing bioenzymes or biomimetic catalytic systems enhance local lactate clearance,alleviating the immunosuppressive effects of the acidic TME.This review comprehensively outlined the lactate-mediated regulatory network,aiming to provide systematic research directions and translational insights for developing more effective anti-tumor therapies.

Objective:To illustrate the clinical modeling and commissioning results of Monte Carlo dose calculation algorithm in RayStation treatment planning system (TPS) for a domestically developed synchrotron-based spot scanning proton therapy system (SAPT-PS-01).Methods:The proton pencil beam model in RayStation required integral depth dose curves, spot profiles and absolute dose as the input beam data. It was not necessary to collect beam parameters with range shifter. The integral depth dose curves of a single spot were measured by an 8 cm parallel ion chamber. A 2-dimensional scintillation detector was used to measure the in-air spot profile at 5 different depths including the isocenter plane. The absolute dose was calibrated by a 0.25 cm parallel ion chamber under the single energy layer irradiation with a field size of 10 cm × 10 cm. After modeling, the results of the beam model and the Monte Carlo dose calculation algorithm were validated from the range, spot profile, point-dose in a spread-out Bragg peak, planar dose in a clinical plan, point dose in an end-to-end test.Results:For the 94 energy layers, the maximum deviation between the calculated and measured range was 0.03 cm. The maximum difference between the calculated and measured in-air spot sigma was 0.015 cm, and the deviation of in-water spot sigma was measured within ±15%. Compared with the measured values, the calculated dose deviation of 138 measured points in the spread-out Bragg peak was within 3%. For the planar dose verification of clinical plans, the TPS-calculated dose distribution of 285 planes agreed well with the measurement with a minimum gamma-passing rate of 90%, and the gamma passing rate of almost 95% of planes were greater than 95%. The point dose measurements for 8 beams in the end-to-end tests under 4 clinical scenarios were within 5%.Conclusions:The acceptable beam model validation results and successful end-to-end test confirm that the Monte Carlo dose calculation algorithm modeling for the synchrotron-based spot scanning proton therapy system is accurate, which is applicable for the design of patient treatment plan.

In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.

Objective To investigate the correlation between rs712 and rs7973450 located at the 3'UTR region of the KRAS gene and the risk of cervical cancer(CC)and cervical intraepithelial neoplasia(CIN)in Chinese Han population in Yunnan province.Methods A total of 2405 individuals(461 subjects with CIN,961 subjects with CC and 983 healthy controls)were enrolled.The SNPs were genotyped used TaqMan assay and the correlation of these SNPs with CIN and CC was analyzed.Results The A allele of rs7973450 might be a protective factor for the occurrence of CIN(P = 0.004,OR= 0.651,95%CI 0.487～0.871)and CC(P = 7.00×10-4,OR= 0.667,95%CI 0.529～0.844).There was no significant difference in allelic and genotypic distribution of rs712 among CIN,CC and Control groups(P>0.017).The haplotype assay showed thatrs712A-rs7973450G was associated with increased risk of CIN(P = 4.00×10-4;OR= 1.714,95%CI 1.269～2.314)and CC(P = 3.84×10-5,OR= 1.667,95%CI 1.305～2.131).While haplotype rs712A-rs7973450A was associated with a lower risk of CC(P = 0.012,OR= 0.790,95%CI 0.658～0.950).Conclusion The A allele of rs7973450 in 3'UTR of KRAS gene might be the protective factor for the occurrence of CIN and CC in a Chinese Han population in Yunnan province.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.