Objective To investigate programmed death including necroptosis,apoptosis,autophagy,ferroptosis,and pyroptosis in bone marrow megakaryocytes of mice during sepsis and its impact on platelet production capacity and coagulation function in mice.Methods C57BL/6J mice were randomly divided into a sham operation group(sham group)and a sepsis model group(CLP group).Peripheral blood platelets and coagulation function were measured by abdominal aortic blood sampling at 24 h postoperatively in both sham and CLP groups.After the mice were sacrificed,long bones of both lower limbs were taken,and bone marrow megakaryocytes were extracted using megakaryocyte separation solution and immunomagnetic bead separation.Laser confocal microscopy was used to observe the activation of programmed death-related marker molecules in mouse bone marrow megakaryocytes.Flow cytometry was used to detect programmed death rate,platelet production phenotype,and platelet surface markers(CD41,CD42b,CD61)of megakaryocytes.Western blotting was used to detect the expression of programmed death-related proteins in megakaryocytes.Results Compared with the sham group,the CLP group showed significant decreases in the number of platelets during acute sepsis(24 h)(P<0.000 1),significant increases in platelet distri-bution width(PDW)and mean platelet volume(MPV)(P<0.01),significant prolonging of thrombin time(TT),prothrombin time(PT),and activated partial thromboplastin time(APTT)(P<0.000 1,P<0.001,P<0.01),and significant reduction in fibrinogen(Fib)(P<0.000 1).Compared with the Con/sham group,the LPS/CLP group exhibited significant increases in the platelet production phenotype of megakaryocyte,the number of PLP in the supernatant,and the expression levels of platelet surface markers(CD41,CD42b,CD61).The rates of megakaryocyte necroptosis/apoptosis,pyroptosis,and ferroptosis were significantly elevated at 24 h post-CLP surgery.Laser confo-cal microscopy showed significant activation of LC3,P-MLKL,Caspase-1,and Fe2+in megakaryocytes of mice after CLP surgery.Western blotting results revealed that the CLP group exhibited a significant increase in the activa-tion rate of necroptosis-related protein P-MLKL(P<0.001),a significant increase in the cleavage of pyroptosis-related proteins GSDMD and GSDMD-N(P<0.01,P<0.001,respectively),a significant increase in the expres-sion of ferroptosis-related protein ACSL4(P<0.01),and a significant decrease in the expression of GPX4(P<0.01)compared to the sham group.Additionally,the CLP group demonstrated significant increases in the expression of apoptosis-related protein Bax,the cleavage of autophagy-related protein LC3B-Ⅱ,and the expression of P62(P<0.05,P<0.001,P<0.001,respectively).Inhibition of apoptosis with programmed cell death inhibitors decreased platelet production function of megakaryocyte,while inhibition of necroptosis and pyroptosis had limited effects on platelet production function of megakaryocyte.Inhibition of ferroptosis and autophagy enhanced platelet production function of megakaryocyte.Conclusion Significant programmed death of megakaryocytes was observed during the acute phase of sepsis(24 h).Among those megakaryocytes,apoptosis is an important mechanism for the differentia-tion of platelet production phenotype and increased platelet production capacity of megakaryocyte.Overactive autophagy and ferroptosis in megakaryocytes lead to megakaryocyte dysfunction,which is an important mechanism for coagulation abnormalities in sepsis.

Objective:To evaluate the performance of the neural network model in segmenting gout tophus in the first metatarsophalangeal（MTP1）joint ultrasound images.Methods:A total of 1 218 tophus images from 381 patients who underwent MTP1 ultrasound examinations in the Affiliated Hospital of Qingdao University between May 2023 and December 2024 were prospectively collected. The images were divided into training，validation，and test sets in a ratio of 7∶2∶1. Multiple neural network models were trained to automatically identify and segment tophus in the images，with physician-annotated tophus regions serving as the reference standard. Model performance was evaluated in the test set，and the impact of tophus characteristics（e.g.，echogenicity，size，and presence of bone erosion）on segmentation efficacy was analyzed.Results:In the test set，CMUNeXt demonstrated superior tophus segmentation performance versus Unet，Unet++，TransUnet，and CMU-Net，achieving an accuracy of 99.1%，precision of 79.1%，recall of 84.6%，intersection over union of 68.8%，and Dice similarity coefficient of 80.2%. Logistic regression identified tophus echogenicity，size，and bone erosion as independent efficacy factors OR（95% CI）=7.275（1.598-33.129），21.303（4.282-105.985），13.520（3.617-50.530），0.076（0.007-0.823）（all P<0.05）. Hypoechoic tophus demonstrated significantly superior segmentation performance compared to mixed-echoic and isoechoic tophus（all P<0.05），and lesions with larger maximum diameters（>10 mm）were segmented more effectively than smaller tophus（ P<0.05）. Conclusions:The CMUNeXt model enables accurate identification and segmentation of tophus in MTP1 ultrasound images，particularly excelling for larger and hypoechoic lesions. This approach holds significant promise for AI-assisted diagnosis of MTP1 gouty arthritis.

Objective:To investigate the effects of thioredoxin reductase 1 (TXNRD1) on ferroptosis and immune function of dendritic cells (DCs) in septic mice, and to provide a basis for improving the immunosuppression in sepsis caused by wound infection.Methods:This study was an experimental research. Sixty male C57BL/6J mice aged 6-8 weeks were subjected to cecal ligation and puncture (CLP) to establish sepsis models. Ten mice were selected at 0 (immediately), 6, 12, 24, 48, and 72 h after CLP surgery, respectively, according to the random number table method. Mouse splenic DCs were isolated using CD11c-positive magnetic beads. The protein expressions of TXNRD1, and anti-ferroptosis proteins solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the cells were detected by Western blotting, the reduced glutathione (GSH) content in the cells was measured by colorimetric assay, the lipid peroxidation level was assessed via live-cell imaging technology, and the levels of major histocompatibility complex class Ⅱ subtype I-A/I-E and leukocyte differentiation antigens CD80 and CD86 were detected by flow cytometry. Another 100 male C57BL/6J mice aged 6-8 weeks were divided into corn oil+sham injury group, corn oil+CLP group, inhibitor+sham injury group, and inhibitor+CLP group according to the random number table method, with 25 mice in each group. Mice in the two inhibitor groups were intraperitoneally injected with TXNRD1 inhibitor auranofin, while mice in the two corn oil groups were intraperitoneally injected with corn oil. One hour later, mice in the two CLP groups underwent CLP surgery to establish sepsis models, while mice in the two sham injury groups underwent sham surgery. Twenty mice from each group were selected to observe survival within 7 d post-surgery, and the survival rate was calculated. At 24 h post-surgery, mouse splenic DCs from the remaining 5 mice in each group were collected for corresponding assays as above.Results:Compared with those at 0 h after CLP surgery, the protein expressions of TXNRD1, GPX4, and SLC7A11 in mouse cells at 24 h after CLP surgery and the protein expression of TXNRD1 in mouse cells at 48 h after CLP surgery were significantly decreased ( P<0.05), the GSH content in mouse cells was significantly decreased at 24 and 48 h after CLP surgery ( P<0.05). The lipid peroxidation level in mouse cells was low at 0, 6, and 12 h after CLP surgery, slightly lower than that at 72 h after CLP surgery; the lipid peroxidation levels in mouse cells at 24 and 48 h after CLP surgery were significantly higher than those at 0, 6, 12, and 72 h after CLP surgery. Compared with those at 0 h after CLP surgery, the levels of I-A/I-E and CD80 in mouse cells at 6, 12, 24, 48, and 72 h after CLP surgery and the levels of CD86 in mouse cells at 12, 24, and 48 h after CLP surgery were significantly increased ( P<0.05). At 24 h post-surgery, the protein expressions of TXNRD1, SLC7A11, and GPX4 in mouse cells in corn oil+CLP group were significantly lower than those in corn oil+sham injury group ( P<0.05), while the protein expressions of TXNRD1, SLC7A11, and GPX4 in mouse cells in inhibitor+CLP group were significantly lower than those in corn oil+CLP group and inhibitor+sham injury group ( P<0.05). At 24 h post-surgery, the content of GSH in mouse cells in corn oil+CLP group was (239±32) μg/mg, which was significantly lower than (366±59) μg/mg in corn oil +sham injury group ( P<0.05); the content of GSH in mouse cells in inhibitor+CLP group was (134±19) μg/mg, which was significantly lower than (355±31) μg/mg in inhibitor+sham injury group and that in corn oil+CLP group (with both P values <0.05). At 24 h post-surgery, the lipid peroxidation level of mouse cells in inhibitor+CLP group was significantly higher than that in the other three groups ( P<0.05). At 24 h post-surgery, the levels of I-A/I-E, CD80, and CD86 in mouse cells in corn oil+CLP group were significantly higher than those in corn oil+sham injury group ( P<0.05), while the levels of I-A/I-E and CD80 in mouse cells in inhibitor+CLP group were significantly higher than those in inhibitor+sham injury group ( P<0.05) but significantly lower than those in corn oil+CLP group ( P<0.05); the level of CD86 in mouse cells in inhibitor+sham injury group was significantly higher than that in corn oil+sham injury group ( P<0.05). Within 7 d post-surgery, the survival rate of mice in inhibitor+CLP group was significantly lower than that in inhibitor+sham injury group and corn oil+CLP group (with χ2 values of 31.19 and 3.91, respectively, both P values <0.05). Conclusions:In septic mice, the expression of TXNRD1 in DCs is reduced, cell ferroptosis is enhanced, and immune function is weakened. The inhibition of TXNRD1 in DCs will exacerbate cell ferroptosis and immune function suppression, and is closely related to the poor prognosis of sepsis.

The pathophysiological mechanisms underlying sepsis is complex, mainly involving excessive inflammatory response and immune dysfunction. The development of nanobiomaterial technology has brought brand-new options for the treatment of sepsis. In the current paper, we discuss the current application status and potential of nanobiomaterials in treatment of sepsis from aspects of antibacterial, anti-inflammatory, targeted regulation of immune cell function, and multi-target combined regulation, pointing out new direction for the future development of therapeutic strategies for sepsis based on nanobiomaterials.

BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.

Objective:To evaluate the performance of the neural network model in segmenting gout tophus in the first metatarsophalangeal（MTP1）joint ultrasound images.Methods:A total of 1 218 tophus images from 381 patients who underwent MTP1 ultrasound examinations in the Affiliated Hospital of Qingdao University between May 2023 and December 2024 were prospectively collected. The images were divided into training，validation，and test sets in a ratio of 7∶2∶1. Multiple neural network models were trained to automatically identify and segment tophus in the images，with physician-annotated tophus regions serving as the reference standard. Model performance was evaluated in the test set，and the impact of tophus characteristics（e.g.，echogenicity，size，and presence of bone erosion）on segmentation efficacy was analyzed.Results:In the test set，CMUNeXt demonstrated superior tophus segmentation performance versus Unet，Unet++，TransUnet，and CMU-Net，achieving an accuracy of 99.1%，precision of 79.1%，recall of 84.6%，intersection over union of 68.8%，and Dice similarity coefficient of 80.2%. Logistic regression identified tophus echogenicity，size，and bone erosion as independent efficacy factors OR（95% CI）=7.275（1.598-33.129），21.303（4.282-105.985），13.520（3.617-50.530），0.076（0.007-0.823）（all P<0.05）. Hypoechoic tophus demonstrated significantly superior segmentation performance compared to mixed-echoic and isoechoic tophus（all P<0.05），and lesions with larger maximum diameters（>10 mm）were segmented more effectively than smaller tophus（ P<0.05）. Conclusions:The CMUNeXt model enables accurate identification and segmentation of tophus in MTP1 ultrasound images，particularly excelling for larger and hypoechoic lesions. This approach holds significant promise for AI-assisted diagnosis of MTP1 gouty arthritis.

Objective:To investigate the effects of thioredoxin reductase 1 (TXNRD1) on ferroptosis and immune function of dendritic cells (DCs) in septic mice, and to provide a basis for improving the immunosuppression in sepsis caused by wound infection.Methods:This study was an experimental research. Sixty male C57BL/6J mice aged 6-8 weeks were subjected to cecal ligation and puncture (CLP) to establish sepsis models. Ten mice were selected at 0 (immediately), 6, 12, 24, 48, and 72 h after CLP surgery, respectively, according to the random number table method. Mouse splenic DCs were isolated using CD11c-positive magnetic beads. The protein expressions of TXNRD1, and anti-ferroptosis proteins solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the cells were detected by Western blotting, the reduced glutathione (GSH) content in the cells was measured by colorimetric assay, the lipid peroxidation level was assessed via live-cell imaging technology, and the levels of major histocompatibility complex class Ⅱ subtype I-A/I-E and leukocyte differentiation antigens CD80 and CD86 were detected by flow cytometry. Another 100 male C57BL/6J mice aged 6-8 weeks were divided into corn oil+sham injury group, corn oil+CLP group, inhibitor+sham injury group, and inhibitor+CLP group according to the random number table method, with 25 mice in each group. Mice in the two inhibitor groups were intraperitoneally injected with TXNRD1 inhibitor auranofin, while mice in the two corn oil groups were intraperitoneally injected with corn oil. One hour later, mice in the two CLP groups underwent CLP surgery to establish sepsis models, while mice in the two sham injury groups underwent sham surgery. Twenty mice from each group were selected to observe survival within 7 d post-surgery, and the survival rate was calculated. At 24 h post-surgery, mouse splenic DCs from the remaining 5 mice in each group were collected for corresponding assays as above.Results:Compared with those at 0 h after CLP surgery, the protein expressions of TXNRD1, GPX4, and SLC7A11 in mouse cells at 24 h after CLP surgery and the protein expression of TXNRD1 in mouse cells at 48 h after CLP surgery were significantly decreased ( P<0.05), the GSH content in mouse cells was significantly decreased at 24 and 48 h after CLP surgery ( P<0.05). The lipid peroxidation level in mouse cells was low at 0, 6, and 12 h after CLP surgery, slightly lower than that at 72 h after CLP surgery; the lipid peroxidation levels in mouse cells at 24 and 48 h after CLP surgery were significantly higher than those at 0, 6, 12, and 72 h after CLP surgery. Compared with those at 0 h after CLP surgery, the levels of I-A/I-E and CD80 in mouse cells at 6, 12, 24, 48, and 72 h after CLP surgery and the levels of CD86 in mouse cells at 12, 24, and 48 h after CLP surgery were significantly increased ( P<0.05). At 24 h post-surgery, the protein expressions of TXNRD1, SLC7A11, and GPX4 in mouse cells in corn oil+CLP group were significantly lower than those in corn oil+sham injury group ( P<0.05), while the protein expressions of TXNRD1, SLC7A11, and GPX4 in mouse cells in inhibitor+CLP group were significantly lower than those in corn oil+CLP group and inhibitor+sham injury group ( P<0.05). At 24 h post-surgery, the content of GSH in mouse cells in corn oil+CLP group was (239±32) μg/mg, which was significantly lower than (366±59) μg/mg in corn oil +sham injury group ( P<0.05); the content of GSH in mouse cells in inhibitor+CLP group was (134±19) μg/mg, which was significantly lower than (355±31) μg/mg in inhibitor+sham injury group and that in corn oil+CLP group (with both P values <0.05). At 24 h post-surgery, the lipid peroxidation level of mouse cells in inhibitor+CLP group was significantly higher than that in the other three groups ( P<0.05). At 24 h post-surgery, the levels of I-A/I-E, CD80, and CD86 in mouse cells in corn oil+CLP group were significantly higher than those in corn oil+sham injury group ( P<0.05), while the levels of I-A/I-E and CD80 in mouse cells in inhibitor+CLP group were significantly higher than those in inhibitor+sham injury group ( P<0.05) but significantly lower than those in corn oil+CLP group ( P<0.05); the level of CD86 in mouse cells in inhibitor+sham injury group was significantly higher than that in corn oil+sham injury group ( P<0.05). Within 7 d post-surgery, the survival rate of mice in inhibitor+CLP group was significantly lower than that in inhibitor+sham injury group and corn oil+CLP group (with χ2 values of 31.19 and 3.91, respectively, both P values <0.05). Conclusions:In septic mice, the expression of TXNRD1 in DCs is reduced, cell ferroptosis is enhanced, and immune function is weakened. The inhibition of TXNRD1 in DCs will exacerbate cell ferroptosis and immune function suppression, and is closely related to the poor prognosis of sepsis.

The pathophysiological mechanisms underlying sepsis is complex, mainly involving excessive inflammatory response and immune dysfunction. The development of nanobiomaterial technology has brought brand-new options for the treatment of sepsis. In the current paper, we discuss the current application status and potential of nanobiomaterials in treatment of sepsis from aspects of antibacterial, anti-inflammatory, targeted regulation of immune cell function, and multi-target combined regulation, pointing out new direction for the future development of therapeutic strategies for sepsis based on nanobiomaterials.

Objective To investigate programmed death including necroptosis,apoptosis,autophagy,ferroptosis,and pyroptosis in bone marrow megakaryocytes of mice during sepsis and its impact on platelet production capacity and coagulation function in mice.Methods C57BL/6J mice were randomly divided into a sham operation group(sham group)and a sepsis model group(CLP group).Peripheral blood platelets and coagulation function were measured by abdominal aortic blood sampling at 24 h postoperatively in both sham and CLP groups.After the mice were sacrificed,long bones of both lower limbs were taken,and bone marrow megakaryocytes were extracted using megakaryocyte separation solution and immunomagnetic bead separation.Laser confocal microscopy was used to observe the activation of programmed death-related marker molecules in mouse bone marrow megakaryocytes.Flow cytometry was used to detect programmed death rate,platelet production phenotype,and platelet surface markers(CD41,CD42b,CD61)of megakaryocytes.Western blotting was used to detect the expression of programmed death-related proteins in megakaryocytes.Results Compared with the sham group,the CLP group showed significant decreases in the number of platelets during acute sepsis(24 h)(P<0.000 1),significant increases in platelet distri-bution width(PDW)and mean platelet volume(MPV)(P<0.01),significant prolonging of thrombin time(TT),prothrombin time(PT),and activated partial thromboplastin time(APTT)(P<0.000 1,P<0.001,P<0.01),and significant reduction in fibrinogen(Fib)(P<0.000 1).Compared with the Con/sham group,the LPS/CLP group exhibited significant increases in the platelet production phenotype of megakaryocyte,the number of PLP in the supernatant,and the expression levels of platelet surface markers(CD41,CD42b,CD61).The rates of megakaryocyte necroptosis/apoptosis,pyroptosis,and ferroptosis were significantly elevated at 24 h post-CLP surgery.Laser confo-cal microscopy showed significant activation of LC3,P-MLKL,Caspase-1,and Fe2+in megakaryocytes of mice after CLP surgery.Western blotting results revealed that the CLP group exhibited a significant increase in the activa-tion rate of necroptosis-related protein P-MLKL(P<0.001),a significant increase in the cleavage of pyroptosis-related proteins GSDMD and GSDMD-N(P<0.01,P<0.001,respectively),a significant increase in the expres-sion of ferroptosis-related protein ACSL4(P<0.01),and a significant decrease in the expression of GPX4(P<0.01)compared to the sham group.Additionally,the CLP group demonstrated significant increases in the expression of apoptosis-related protein Bax,the cleavage of autophagy-related protein LC3B-Ⅱ,and the expression of P62(P<0.05,P<0.001,P<0.001,respectively).Inhibition of apoptosis with programmed cell death inhibitors decreased platelet production function of megakaryocyte,while inhibition of necroptosis and pyroptosis had limited effects on platelet production function of megakaryocyte.Inhibition of ferroptosis and autophagy enhanced platelet production function of megakaryocyte.Conclusion Significant programmed death of megakaryocytes was observed during the acute phase of sepsis(24 h).Among those megakaryocytes,apoptosis is an important mechanism for the differentia-tion of platelet production phenotype and increased platelet production capacity of megakaryocyte.Overactive autophagy and ferroptosis in megakaryocytes lead to megakaryocyte dysfunction,which is an important mechanism for coagulation abnormalities in sepsis.

Objective:To evaluate the efficacy and safety of the gemcitabine combined with oxaliplatin (GEMOX) regimen in the postoperative adjuvant treatment for the patients with cisplatin-intolerant uroepithelial cancer.Methods:The clinical data of 98 patients with uroepithelial carcinoma intolerant to cisplatin chemotherapy who underwent radical surgery from August 2017 to October 2022 at Drum Tower Hospital of Nanjing University School of Medicine were retrospectively analysed. The patients were divided into the adjuvant chemotherapy group and the observation group according to whether or not they underwent adjuvant chemotherapy after surgery. The adjuvant chemotherapy group received postoperative chemotherapy with the GEMOX regimen (gemcitabine 1 000 mg/m 2 intravenously on days 1 and 8, oxaliplatin 130 mg/m 2 intravenously on day 2, every 3 weeks as a cycle), and the observation group did not undergo postoperative adjuvant chemotherapy. In the adjuvant chemotherapy group, there were 33 males and 10 females, the patients’ age was (67.8±7.3) years old, 33 cases with estimated glomerular filtration rate (eGFR) ≤60 ml/(min·1.73m 2), and 10 cases with a Eastern Cooperative Oncology Group (ECOG) functional status score of >1. The postoperative pathology showed 39 cases were in stage T 3, 4 cases in stage T 4, and lymph node positivity (N+ ) was found in 10 cases. There were 55 cases in the observation group, with 42 males and 13 females and the age of (70.7±7.7) years old. Forty-two of them had an eGFR ≤60 ml/(min·1.73m 2), and 13 of them had a ECOG score of >1. The postoperative pathology showed 48 cases were in stage T 3, 7 cases in stage T 4, and 13 cases of N+. The changes in renal function, ECOG scores, and adverse reactions were observed in adjuvant chemotherapy group. Kaplan-Meier method was used to estimate the survival rate, and the log-rank test was used to compare the survival rate between groups. Multifactorial Cox regression was used to analyse the correlation between age, lymph nodes, whether or not to combine with adjuvant chemotherapy and the survival of patients. Results:All patients in this study were followed up for 3 to 75 months, with a median follow-up time of 22 (14, 34) months. The recurrence rates were 83.6%(46/55) and 65.1%(28/43) in the observation and adjuvant chemotherapy groups, respectively, and the disease mortality rates were 52.7%(29/55) and 27.9%(12/43), respectively. The results of the Kaplan-Meier survival analyses showed that the 1-, 2- and 3-year disease-free survival rates in the adjuvant chemotherapy group were 62.8%, 48.6% and 41.1%, respectively, and the 1-, 2- and 3-year overall survival rates were 86.0%, 79.0% and 76.4%, respectively. The 1-, 2- and 3-year disease-free survival rates of the observation group were 58.2%, 22.6% and 9.6%, respectively, and the 1-, 2- and 3-year overall survival rates were 78.2%, 49.4% and 42.8%, respectively. The adjuvant chemotherapy group had an advantage over the observation group regarding disease-free and overall survival rates (all P<0.05). The results of multifactorial Cox regression analysis suggested that the functional status score and the presence or absence of positive lymph nodes, diabetes mellitus, and co-adjuvant chemotherapy were independent risk factors affecting the survival of the patients ( P<0.05). Forty-three cases had 1 to 6 courses of adjuvant chemotherapy, with a median course of 4 (2, 4). In terms of safety, the most common adverse reaction in the gastrointestinal tract was loss of appetite (53.4%, 23/43), the most common grade 1 to 2 adverse reaction in myelosuppression was a decrease in haemoglobin (51.2%, 22/43), and the most common grade 3 to 4 adverse reaction was thrombocytopenia (9.3%, 4/43). The eGFR of 33 patients with renal insufficiency in the adjuvant chemotherapy group was higher after each administration cycle than before ( P<0.05), and renal function did not deteriorate with the increase in administration cycles. Ten patients with a ECOG score of 2 remained with a score of 2 after chemotherapy. Conclusions:In patients with cisplatin-intolerant uroepithelial cancer, gemcitabine in combination with an oxaliplatin regimen improves the overall survival of patients. At the same time, it is well tolerated without increasing nephrotoxicity, making it an optional postoperative adjuvant treatment for patients with cisplatin-intolerant uroepithelial cancer.