Objective:To evaluate the relationship between superoxide dismutase 2 (SOD2) lactylation and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy-ferroptosis during cerebral ischemia-reperfusion (IR) in mice.Methods:Thirty-six clean-grade male C57BL/6 mice, aged 8-10 weeks, weighing 22-25 g, were divided into 4 groups ( n=9 each) using a table of random numbers: sham operation group (Sham group), cerebral IR group (IR group), IR+ glycolysis inhibitor 2-DG group (IR+ 2-DG group), and IR+ 2-DG+ NCOA4 overexpression group (IR+ 2-DG+ LvNCOA4 group). The model of cerebral IR injury was established by occlusion of the middle cerebral artery for 1 h followed by 24 h of reperfusion using the intraluminal suture method in anesthetized animals. 2-DG 250 mg/kg was intraperitoneally injected at 90 min before ischemia in IR+ 2-DG and IR+ 2-DG+ LvNCOA4 groups. The lentivirus overexpressing NCOA4 2 μl was injected into the ventricles at 7 days before ischemia in IR+ 2-DG+ LvNCOA4 group. The percentage of cerebral infarct volume was determined, the viable neurons were counted, and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) were measured by enzyme-linked immunosorbent assay. The expression of SOD2, lysine 114 lactylation of superoxide dismutase 2 (SOD2-K114la), NCOA4, microtubule-associated protein 1 light chain 3β (LC3B), and acyl-CoA synthetase long-chain family member 4 (ACSL4) was determined by Western blot. Mitochondrial morphology was examined by electron microscopy. Results:Compared with Sham group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, the expression of SOD2-K114la, NCOA4, LC3B and ACSL4 was up-regulated, the expression of SOD2 was down-regulated ( P<0.05), and the mitochondrial injury was aggravated in IR group. Compared with IR group, the percentage of cerebral infarct volume was significantly decreased, the number of viable neurons was increased, the mitochondrial injury was alleviated, the levels of ROS and MDA were decreased, the content of GSH was increased, the expression of SOD2-K114la, NCOA4 and ACSL4 was down-regulated, and the expression of SOD2 and LC3B was up-regulated in IR+ 2-DG group ( P<0.05). Compared with IR+ 2-DG group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, and the expression of NCOA4, LC3B and ACSL4 was up-regulated ( P<0.05), no significant change was found in the expression of SOD2 and SOD2-K114la ( P>0.05), and the mitochondrial injury was aggravated in IR+ 2-DG+ LvNCOA4 group. Conclusions:SOD2 lactylation promotes NCOA4-mediated ferritinophagy-ferroptosis by enhancing oxidative stress, thereby contributing to the cerebral IR injury in mice.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Objective:To compare the clinical efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma.Methods:A prospective, randomized, controlled study was conducted. Patients with melasma were collected from the Department of Dermatology, Guangzhou Dermatology Hospital from March 2023 to May 2024, and divided into a nanomicroneedle group (receiving nanomicroneedle-mediated delivery of tranexamic acid) and an ultrasound group (receiving ultrasound-mediated delivery of tranexamic acid) using the random number table method. Both groups underwent the treatment once a week for a total of 8 sessions. At week 12, outcomes including melasma area and severity index (MASI) scores, treatment response rates, VISIA brown spot scores, pain scores, and adverse reactions were evaluated and compared between the two groups. Statistical analyses were carried out using two-independent-sample t test, Mann-Whitney U test, and chi-square test. Results:A total of 80 patients with melasma were included, with 40 in each group. In the nanomicroneedle group, the patients were aged 40.35 ± 7.39 years (range: 25 - 55 years), with the disease duration being 8.45 ± 4.77 months (range: 1 - 16 months) ; in the ultrasound group, the patients were aged 40.25 ± 7.76 years (range: 25 - 55 years), and their disease duration was 10.45 ± 5.07 months (range: 2 - 17 months) ; there were no significant differences in ages or disease duration between the two groups (both P > 0.05). At week 12, both groups demonstrated reduced MASI scores compared to baseline scores, and the MASI scores were significantly lower in the nanomicroneedle group ( M[ Q1, Q3]: 5.80[4.20, 9.35]) than in the ultrasound group (8.65[5.70, 10.80], Z = 2.50, P = 0.012). The overall response rate was significantly higher in the nanomicroneedle group (97.5%, 39/40) than in the ultrasound group (55.0%, 22/40; χ2 = 19.95, P < 0.001). The lateral facial VISIA brown spot scores were also significantly lower in the nanomicroneedle group (left side: 126.18 ± 36.54 points; right side: 138.50 ± 40.76 points) than in the ultrasound group (left side: 142.37 ± 32.40 points; right side: 157.13 ± 39.59 points; t = -2.10, -2.07, P = 0.039, 0.041, respectively). In the nanomicroneedle group, the pain scores were 4.12 ± 1.47 points, and varying severity of adverse reactions such as erythema, edema and dryness occurred after operation, all of which resolved spontaneously within 48 hours. No marked adverse reactions were observed in the ultrasound group. Conclusion:Nanomicroneedle-mediated delivery of tranexamic acid demonstrated superior clinical efficacy and favorable safety profiles compared to the ultrasound-mediated delivery, providing more options for the treatment of melasma.

Objective:To explore the role of lactate in Superoxide dismutase 2 (SOD2) lactylation in cerebral ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomLy (random number) divided into 4 groups: sham operation group (Sham group), Middle Cerebral Artery Occlusion/Reperfusion group (MCAO/R group), Middle Cerebral Artery Occlusion/Reperfusion+2-Deoxy-D-glucose group (MCAO/R+2-DG group), Middle Cerebral Artery Occlusion/Reperfusion+sodium lactate group (MCAO/R+Nala group). Cerebral ischemia reperfusion injury model was established in the mice of MCAO/R group using the thread occlusion. In the MCAO/R+2-DG group, mice received an intraperitoneal injection of 250 mg/kg of 2-DG 90 min before ischemia. Mice in the MCAO/R+ Nala group was given an intraventricular injection of 2 μL of 100 mmol/L Nala 24 h before ischemia. Commercial kits was used to detect lactate levels, Hematoxylin & Eosin Staining (HE) was employed to observe cell morphology, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed to assess cell apoptosis, and immunofluorescence was utilized to detect reactive oxygen species (ROS). Western blot was conducted to measure SOD2, Superoxide Dismutase 2 Lysine 114 Lactylation(SOD2-K114la), Iron regulatory protein 2(IRP2) and transferrin receptor protein 1(TFR1) levels. The above indicators were analyzed and compared by one-way variance.Results:Compared with the Sham group, the MCAO/R group showed increased levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2 and TFR1[lactate: (0.608±0.064) vs. (0.376±0.030), P<0.005; SOD2-K114la: (2.311±0.146) vs. (1.009±0.073), P<0.0005; TUNEL positive rate: (35.420±2.832) vs. (0.294±0.147), P<0.0001; ROS: (3.415±0.229) vs. (1.166±0.155), P<0.0001; IRP2: (1.735±0.125) vs. (1.000±0.000), P<0.0001; TFR1: (1.611±0.058) vs. (1.000±0.000), P<0.0001], while SOD2 decreased[(0.545±0.062) vs. (1.082±0.088), P<0.0001]. HE staining indicated brain damage. Compared with the MCAO/R group, the MCAO/R+2-DG group showed reduced levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2, and TFR1[lactate: (0.453±0.047) vs. (0.608±0.064), P<0.05; SOD2-K114la: (1.764±0.188) vs. (2.311±0.146), P<0.05; TUNEL positive rate: (23.800±3.168) vs. (35.420±2.832), P<0.005; ROS: (2.640±0.213) vs. (3.415±0.229), P<0.005; IRP2: (1.463±0.055) vs. (1.735±0.125), P<0.05; TFR1: (1.252±0.081) vs. (1.611±0.058), P<0.005], with higher level of SOD2 [(0.727±0.026) vs. (0.545±0.062), P<0.05]. Meanwhile, HE staining indicated reduced damage. Compared with the MCAO/R group, the MCAO/R+Nala group showed increased levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2 and TFR1[lactate: (1.021±0.051) vs. (0.608±0.064), P<0.0001; SOD2-K114la: (3.479±0.275) vs. (2.311±0.146), P<0.0005; TUNEL positive rate: (53.430±3.551) vs. (35.420±2.832), P<0.0001; ROS: (4.687±0.253) vs. (3.415±0.229), P<0.0001; IRP2: (2.463±0.117) vs. (1.735±0.125), P<0.0001; TFR1: (2.209±0.094) vs. (1.611±0.058), P<0.0001], with decreased levels of SOD2 [(0.286±0.040) vs. (0.545±0.062), P<0.0001]. And HE staining revealed worsened braindamage. Conclusions:Increased lactate levels can enhance the lactylation of SOD2, exacerbating brain damage after Cerebral ischemia reperfusion injury(CIRI). Inhibiting lactate production may alleviate brain injury by regulating iron Metabolism.

Objective To analyze the impact of the National Centralized Drug Procurement Policy(hereinafter referred to as the"centralized procurement policy")on the utilization of breast cancer treatment drugs in a specialized cancer hospital.Methods The defined daily dose(DDD)method was used to compare the daily drug cost(DDC),drug utilization frequency(DDDs),and affordability of letrozole,anastrozole,and capecitabine before and after the implementation of the centralized pro-curement policy in a tertiary specialized cancer hospital in Guangzhou.Results and Conclusion After the policy implementa-tion,the DDC of all three drugs decreased.The out-of-pocket DDC for the selected drugs remained stable or decreased,while the out-of-pocket DDC for both originator drugs and generic drugs increased,with a more pronounced increase for originator drugs.The proportion of DDDs for the selected drugs increased post-policy.The centralized procurement policy not only reduced the prices of selected drugs but also drove down the prices of generic and originator drugs.It is recommended to further expand the scope of centralized procurement for anticancer drugs and the types of cancers covered,as well as to establish a transitional mech-anism for medical insurance payment standards.

Objective:To investigate the phenomenon of hippocampal ferroptosis and its change in a rat model of chronic constriction injury(CCI)of the sciatic nerve,as well as the association between hippocampal ferroptosis and emotional disorders induced by neuro-pathic pain.Methods:A total of 32 male Sprague-Dawley rats were randomly divided into Sham group,CCI group,CCI+F group,and CCI+E group,with 8 rats in each group.The rats in the CCI+F group and the CCI+E group were given intraperitoneal injection of Ferrostatin-1(10 mg/kg)and Erastin(10 mg/kg),respectively,since day 7 after surgery for two consecutive days.Mechanical with-drawal threshold(MWT),paw withdrawal latency(PWL),and open field test(OFT)were measured before surgery and on days 7 and 14 after surgery.On day 14 after surgery,the rats were sacrificed to col-lect hippocampal tissue;Western blot was used to measure the levels of GPX4,xCT,and FTH1;related kits were used to measure the expression levels of MDA and GSH;HE staining,Nissl staining,and immunofluorescent staining were performed;transmission electron microscopy was used to observe the structural changes of the mito-chondria.Results:In terms of behavioristics,compared with the Sham group,the CCI group had significant reductions in MWT and PWL on day 7 after surgery(P<0.001),with further reductions from day 7 to day 14 after surgery(P<0.001);compared with the CCI group,the CCI+F group had significant increases in MWT and PWL on day 14 after surgery(P<0.001),and the CCI+E group had no significant change in MWT and a significant reduction in PWL(P<0.01).In terms of the OFT test,compared with the Sham group,the CCI group had significant reductions in total distance and number of central squares crossed(P<0.001)and a significant increase in immobility time(P<0.001);compared with the CCI group,the CCI+F group had significant increases in total distance and number of central squares crossed and a significant reduction in immobility time,while the CCI+E group had no significant changes in these indi-ces.In terms of biochemical results,compared with the Sham group,the CCI group had significant reductions in GPX4,xCT,and FTH1(P<0.01),a significant increase in MDA,and a significant reduction in GSH;compared with the CCI group,the CCI+F group had sig-nificant increases in GPX4,xCT,and FTH1(P<0.05),a significant reduction in MDA(P<0.001),and a significant increase in GSH(P<0.01),and the CCI+E group had significant reductions in xCT and FTH1,with no significant changes in MDA and GSH.In terms of morphology,compared with the Sham group,the CCI group had damage and necrosis of hippocampal neurons,significant reductions in Nissl bodies and c-Fos level(P<0.05),and significantly damaged mitochondrial cristae on day 14 after surgery;compared with the CCI group,the CCI+F group had intact structures of hippocampal neurons,significant increases in Nissl bodies and c-Fos(P<0.05),and relatively intact mitochondria,while there were no significant differences in c-Fos and Nissl bodies between the CCI+E group and the CCI group.The pairwise linear correlation analysis of PWL,MWT,GPX4,OFT,and c-Fos on day 14 after surgery showed a signifi-cantly positive correlation between any two indicators(P<0.01).Conclusion:Peripheral nerve injury triggers ferroptosis in the hippo-campus and causes anxiety and depression,thereby aggravating ferroptosis and accelerating the development of central hyperalgesia.

Objective To analyze the impact of the National Centralized Drug Procurement Policy(hereinafter referred to as the"centralized procurement policy")on the utilization of breast cancer treatment drugs in a specialized cancer hospital.Methods The defined daily dose(DDD)method was used to compare the daily drug cost(DDC),drug utilization frequency(DDDs),and affordability of letrozole,anastrozole,and capecitabine before and after the implementation of the centralized pro-curement policy in a tertiary specialized cancer hospital in Guangzhou.Results and Conclusion After the policy implementa-tion,the DDC of all three drugs decreased.The out-of-pocket DDC for the selected drugs remained stable or decreased,while the out-of-pocket DDC for both originator drugs and generic drugs increased,with a more pronounced increase for originator drugs.The proportion of DDDs for the selected drugs increased post-policy.The centralized procurement policy not only reduced the prices of selected drugs but also drove down the prices of generic and originator drugs.It is recommended to further expand the scope of centralized procurement for anticancer drugs and the types of cancers covered,as well as to establish a transitional mech-anism for medical insurance payment standards.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Objective:To compare the clinical efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma.Methods:A prospective, randomized, controlled study was conducted. Patients with melasma were collected from the Department of Dermatology, Guangzhou Dermatology Hospital from March 2023 to May 2024, and divided into a nanomicroneedle group (receiving nanomicroneedle-mediated delivery of tranexamic acid) and an ultrasound group (receiving ultrasound-mediated delivery of tranexamic acid) using the random number table method. Both groups underwent the treatment once a week for a total of 8 sessions. At week 12, outcomes including melasma area and severity index (MASI) scores, treatment response rates, VISIA brown spot scores, pain scores, and adverse reactions were evaluated and compared between the two groups. Statistical analyses were carried out using two-independent-sample t test, Mann-Whitney U test, and chi-square test. Results:A total of 80 patients with melasma were included, with 40 in each group. In the nanomicroneedle group, the patients were aged 40.35 ± 7.39 years (range: 25 - 55 years), with the disease duration being 8.45 ± 4.77 months (range: 1 - 16 months) ; in the ultrasound group, the patients were aged 40.25 ± 7.76 years (range: 25 - 55 years), and their disease duration was 10.45 ± 5.07 months (range: 2 - 17 months) ; there were no significant differences in ages or disease duration between the two groups (both P > 0.05). At week 12, both groups demonstrated reduced MASI scores compared to baseline scores, and the MASI scores were significantly lower in the nanomicroneedle group ( M[ Q1, Q3]: 5.80[4.20, 9.35]) than in the ultrasound group (8.65[5.70, 10.80], Z = 2.50, P = 0.012). The overall response rate was significantly higher in the nanomicroneedle group (97.5%, 39/40) than in the ultrasound group (55.0%, 22/40; χ2 = 19.95, P < 0.001). The lateral facial VISIA brown spot scores were also significantly lower in the nanomicroneedle group (left side: 126.18 ± 36.54 points; right side: 138.50 ± 40.76 points) than in the ultrasound group (left side: 142.37 ± 32.40 points; right side: 157.13 ± 39.59 points; t = -2.10, -2.07, P = 0.039, 0.041, respectively). In the nanomicroneedle group, the pain scores were 4.12 ± 1.47 points, and varying severity of adverse reactions such as erythema, edema and dryness occurred after operation, all of which resolved spontaneously within 48 hours. No marked adverse reactions were observed in the ultrasound group. Conclusion:Nanomicroneedle-mediated delivery of tranexamic acid demonstrated superior clinical efficacy and favorable safety profiles compared to the ultrasound-mediated delivery, providing more options for the treatment of melasma.

Objective:To evaluate the relationship between superoxide dismutase 2 (SOD2) lactylation and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy-ferroptosis during cerebral ischemia-reperfusion (IR) in mice.Methods:Thirty-six clean-grade male C57BL/6 mice, aged 8-10 weeks, weighing 22-25 g, were divided into 4 groups ( n=9 each) using a table of random numbers: sham operation group (Sham group), cerebral IR group (IR group), IR+ glycolysis inhibitor 2-DG group (IR+ 2-DG group), and IR+ 2-DG+ NCOA4 overexpression group (IR+ 2-DG+ LvNCOA4 group). The model of cerebral IR injury was established by occlusion of the middle cerebral artery for 1 h followed by 24 h of reperfusion using the intraluminal suture method in anesthetized animals. 2-DG 250 mg/kg was intraperitoneally injected at 90 min before ischemia in IR+ 2-DG and IR+ 2-DG+ LvNCOA4 groups. The lentivirus overexpressing NCOA4 2 μl was injected into the ventricles at 7 days before ischemia in IR+ 2-DG+ LvNCOA4 group. The percentage of cerebral infarct volume was determined, the viable neurons were counted, and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) were measured by enzyme-linked immunosorbent assay. The expression of SOD2, lysine 114 lactylation of superoxide dismutase 2 (SOD2-K114la), NCOA4, microtubule-associated protein 1 light chain 3β (LC3B), and acyl-CoA synthetase long-chain family member 4 (ACSL4) was determined by Western blot. Mitochondrial morphology was examined by electron microscopy. Results:Compared with Sham group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, the expression of SOD2-K114la, NCOA4, LC3B and ACSL4 was up-regulated, the expression of SOD2 was down-regulated ( P<0.05), and the mitochondrial injury was aggravated in IR group. Compared with IR group, the percentage of cerebral infarct volume was significantly decreased, the number of viable neurons was increased, the mitochondrial injury was alleviated, the levels of ROS and MDA were decreased, the content of GSH was increased, the expression of SOD2-K114la, NCOA4 and ACSL4 was down-regulated, and the expression of SOD2 and LC3B was up-regulated in IR+ 2-DG group ( P<0.05). Compared with IR+ 2-DG group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, and the expression of NCOA4, LC3B and ACSL4 was up-regulated ( P<0.05), no significant change was found in the expression of SOD2 and SOD2-K114la ( P>0.05), and the mitochondrial injury was aggravated in IR+ 2-DG+ LvNCOA4 group. Conclusions:SOD2 lactylation promotes NCOA4-mediated ferritinophagy-ferroptosis by enhancing oxidative stress, thereby contributing to the cerebral IR injury in mice.