Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

BACKGROUND:How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research.The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer(PLGA)composite scaffold modified by lysine-grafted graphene oxide nanoparticles(LGA-g-GO)on osteogenic differentiation and new bone formation. METHODS:PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method.PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution.LGA-g-GO nanoparticles were prepared by chemical grafting method,and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios(1%,2%,and 3%)with PLGA.The micromorphology,hydrophilicity,and protein adsorption capacity of scaffolds of five groups were characterized.MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION:(1)The surface of PLGA scaffolds was smooth and flat under scanning electron microscope,while the surface of the other four scaffolds was rough.The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles.The water contact angle of PLGA/LGA-g-GO(3%)composite scaffolds was lower than that of the other four groups(P<0.05).The protein adsorption capacity of PLGA/LGA-g-GO(1%,2%,and 3%)composite scaffolds was stronger than PLGA and PLGA/GO scaffolds(P<0.05).(2)CCK-8 assay showed that PLGA/LGA-g-GO(2%,3%)composite scaffold could promote the proliferation of MC3T3 cells.Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO(2%,3%)group was higher than that in the other three groups(P<0.05).The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO(1%,2%,and 3%)groups was higher than that in the PLGA group(P<0.05).(3)In summary,PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts,and is conducive to bone regeneration and bone reconstruction after bone injury.

Objective To explore the effects of Mahuang Lianqiao Chixiaodu Decoction on IgA nephropathy model rats and its mechanism based on C3a/C3aR signaling pathway.Methods Nine rats were randomly selected from 30 male Wistar rats as control group(9 rats),the remaining 21 rats were prepared IgA nephropathy models using the bovine serum albumin-lipopolysaccharide-carbon tetrachloride complex immunization method.Finally 18 successfully modeled rats were randomly divided into model group,Chinese medicine group and Western medicine group,Chinese medicine group was treated with Mahuang Lianqiao Chixiaodou Decoction suspension by gavage,the Western medicine group was treated with losartan suspension by gavage,the control group and model group were treated with normal saline by gavage.The intervention lasted for 4 weeks.HE,PAS and Masson staining were used to observe the morphology of renal tissue,the expression of IgA in glomerular mesangial area was detected by immunofluorescence,the contents of IL-6,TNF-α and C3a in renal tissue were detected by ELISA,the protein expressions of C3/C3b/C3c,C3aR,CFB,TLR4 and NF-κBp65 in renal tissue were detected by Western blot,the positive expressions of C3,C3aR and CFB in renal tissue were detected by immunohistochemistry.Results Compared with the control group,the model group showed compensatory expansion of large glomeruli,proliferation of mesangial cells,expansion of mesangial matrix,and strong positive IgA immune complex deposition in mesangial area(P<0.01),the contents of IL-6,TNF-α and C3a in renal tissue significantly increased(P<0.01),the expressions of C3/C3b/C3c,C3aR,CFB,TLR4 and NF-κBp65 protein in renal tissue increased(P<0.05),the positive expressions of C3,C3aR and CFB in renal tissue significantly increased(P<0.01).Compared with the model group,the pathological damage of Chinese medicine group and Western medicine group was alleviated,the deposition of IgA immune complex was significantly reduced(P<0.01),the contents of IL-6 and TNF-α in renal tissue significantly decreased(P<0.01,P<0.05),and the expressions of C3/C3b/C3c,C3aR,CFB,TLR4 and NF-κBp65 protein in renal tissue decreased(P<0.01,P<0.05),the positive expressions of C3,C3aR and CFB in renal tissues decreased(P<0.01).Conclusion Mahuang Lianqiao Chixiaodou Decoction can inhibit the inflammatory response and improve renal pathological damage in IgA nephropathy rats,and the mechanism may be related to the inhibition of alternative pathway complement activation and the regulation of C3a/C3aR and TLR4/NF-κB signaling pathways.

Background and Aims:Pancreatic cancer is one of the most aggressive malignancies of the digestive system and is associated with an inferior prognosis.In recent years,its incidence has shown a trend toward younger onset.Early-onset pancreatic cancer(EOPC),defined as pancreatic cancer diagnosed at≤50 years of age,has been increasing annually and may possess distinct biological and prognostic characteristics.Given the limited data from China,this study aimed to investigate the clinicopathological features and prognostic outcomes of EOPC patients.Methods:Clinical data of 113 patients with EOPC admitted to Xiangya Hospital,Central South University,from January 2017 to December 2023 were retrospectively analyzed.Variables included demographic characteristics,clinicopathological features,and survival information.Kaplan-Meier survival curves were plotted,and differences in survival between the surgical and non-surgical groups were compared.Results:The median age at diagnosis was 46(42-49)years,and males accounted for 65.49%of cases.Blood type A(40.71%)and type O(34.51%)were most common.The main presenting symptoms were abdominal pain(69.91%),weight loss(62.83%),jaundice(43.36%),and abdominal distension(36.28%).Imaging findings showed bile duct dilation in 32.74%,pancreatic duct dilation in 39.82%,vascular invasion in 59.29%,and distant metastasis in 52.21%of patients.Histopathology revealed that adenocarcinoma and ductal adenocarcinoma accounted for 93.81%of all cases,with predominantly moderate or poor differentiation(76.10%).Tumors were the most frequently located in the pancreatic head(65.42%).TNM staging showed lymph node metastasis in 77.88%and stage Ⅳ disease in 52.21%.Laboratory tests demonstrated markedly elevated CA19-9 levels.Kaplan-Meier analysis indicated a median overall survival of 18.6 months for the entire cohort,with significantly longer survival in the surgical group compared with the non-surgical group(29.4 months vs.13.8 months,P=0.001 5).Conclusion:EOPC predominantly affects males and tends to arise in the pancreatic head.It is often diagnosed at an advanced stage or with distant metastasis and is characterized by poor differentiation and strong invasiveness.Surgical resection markedly improves survival and remains the key to prolonged prognosis.Young individuals presenting with unexplained abdominal pain,weight loss,or jaundice should be carefully evaluated through imaging to enable early diagnosis and timely surgical intervention.Future multicenter,large-sample prospective studies are warranted to validate these findings further.

In 2025,the International Association of Pancreatology(IAP),in collaboration with the American Pancreatic Association,European Pancreatic Club,Indian Pancreas Club,and Japan Pancreas Society,released the International Association of Pancreatology revised guidelines on acute pancreatitis 2025.This edition represents a comprehensive revision of the 2013 guidelines,based on high-quality evidence accumulated over the past decade,particularly randomized controlled trials.The guidelines encompass 18 key areas-including pain management,fluid therapy,nutritional support,management of infected necrosis,complication control,discharge and follow-up,and recurrence prevention-offering a total of 96 recommendations that emphasize individualized treatment.These updates provide important guidance for standardizing clinical practice and improving outcomes in acute pancreatitis,while also indicating future research directions such as the development of targeted therapies.However,some recommendations remain limited by lower evidence quality,uncertain applicability in specific clinical settings,and insufficient consideration of economic burden and cost-effectiveness.

Background and Aims:Pancreatic cancer is one of the most aggressive malignancies of the digestive system and is associated with an inferior prognosis.In recent years,its incidence has shown a trend toward younger onset.Early-onset pancreatic cancer(EOPC),defined as pancreatic cancer diagnosed at≤50 years of age,has been increasing annually and may possess distinct biological and prognostic characteristics.Given the limited data from China,this study aimed to investigate the clinicopathological features and prognostic outcomes of EOPC patients.Methods:Clinical data of 113 patients with EOPC admitted to Xiangya Hospital,Central South University,from January 2017 to December 2023 were retrospectively analyzed.Variables included demographic characteristics,clinicopathological features,and survival information.Kaplan-Meier survival curves were plotted,and differences in survival between the surgical and non-surgical groups were compared.Results:The median age at diagnosis was 46(42-49)years,and males accounted for 65.49%of cases.Blood type A(40.71%)and type O(34.51%)were most common.The main presenting symptoms were abdominal pain(69.91%),weight loss(62.83%),jaundice(43.36%),and abdominal distension(36.28%).Imaging findings showed bile duct dilation in 32.74%,pancreatic duct dilation in 39.82%,vascular invasion in 59.29%,and distant metastasis in 52.21%of patients.Histopathology revealed that adenocarcinoma and ductal adenocarcinoma accounted for 93.81%of all cases,with predominantly moderate or poor differentiation(76.10%).Tumors were the most frequently located in the pancreatic head(65.42%).TNM staging showed lymph node metastasis in 77.88%and stage Ⅳ disease in 52.21%.Laboratory tests demonstrated markedly elevated CA19-9 levels.Kaplan-Meier analysis indicated a median overall survival of 18.6 months for the entire cohort,with significantly longer survival in the surgical group compared with the non-surgical group(29.4 months vs.13.8 months,P=0.001 5).Conclusion:EOPC predominantly affects males and tends to arise in the pancreatic head.It is often diagnosed at an advanced stage or with distant metastasis and is characterized by poor differentiation and strong invasiveness.Surgical resection markedly improves survival and remains the key to prolonged prognosis.Young individuals presenting with unexplained abdominal pain,weight loss,or jaundice should be carefully evaluated through imaging to enable early diagnosis and timely surgical intervention.Future multicenter,large-sample prospective studies are warranted to validate these findings further.

In 2025,the International Association of Pancreatology(IAP),in collaboration with the American Pancreatic Association,European Pancreatic Club,Indian Pancreas Club,and Japan Pancreas Society,released the International Association of Pancreatology revised guidelines on acute pancreatitis 2025.This edition represents a comprehensive revision of the 2013 guidelines,based on high-quality evidence accumulated over the past decade,particularly randomized controlled trials.The guidelines encompass 18 key areas-including pain management,fluid therapy,nutritional support,management of infected necrosis,complication control,discharge and follow-up,and recurrence prevention-offering a total of 96 recommendations that emphasize individualized treatment.These updates provide important guidance for standardizing clinical practice and improving outcomes in acute pancreatitis,while also indicating future research directions such as the development of targeted therapies.However,some recommendations remain limited by lower evidence quality,uncertain applicability in specific clinical settings,and insufficient consideration of economic burden and cost-effectiveness.

Objective To explore the effects of Mahuang Lianqiao Chixiaodu Decoction on IgA nephropathy model rats and its mechanism based on C3a/C3aR signaling pathway.Methods Nine rats were randomly selected from 30 male Wistar rats as control group(9 rats),the remaining 21 rats were prepared IgA nephropathy models using the bovine serum albumin-lipopolysaccharide-carbon tetrachloride complex immunization method.Finally 18 successfully modeled rats were randomly divided into model group,Chinese medicine group and Western medicine group,Chinese medicine group was treated with Mahuang Lianqiao Chixiaodou Decoction suspension by gavage,the Western medicine group was treated with losartan suspension by gavage,the control group and model group were treated with normal saline by gavage.The intervention lasted for 4 weeks.HE,PAS and Masson staining were used to observe the morphology of renal tissue,the expression of IgA in glomerular mesangial area was detected by immunofluorescence,the contents of IL-6,TNF-α and C3a in renal tissue were detected by ELISA,the protein expressions of C3/C3b/C3c,C3aR,CFB,TLR4 and NF-κBp65 in renal tissue were detected by Western blot,the positive expressions of C3,C3aR and CFB in renal tissue were detected by immunohistochemistry.Results Compared with the control group,the model group showed compensatory expansion of large glomeruli,proliferation of mesangial cells,expansion of mesangial matrix,and strong positive IgA immune complex deposition in mesangial area(P<0.01),the contents of IL-6,TNF-α and C3a in renal tissue significantly increased(P<0.01),the expressions of C3/C3b/C3c,C3aR,CFB,TLR4 and NF-κBp65 protein in renal tissue increased(P<0.05),the positive expressions of C3,C3aR and CFB in renal tissue significantly increased(P<0.01).Compared with the model group,the pathological damage of Chinese medicine group and Western medicine group was alleviated,the deposition of IgA immune complex was significantly reduced(P<0.01),the contents of IL-6 and TNF-α in renal tissue significantly decreased(P<0.01,P<0.05),and the expressions of C3/C3b/C3c,C3aR,CFB,TLR4 and NF-κBp65 protein in renal tissue decreased(P<0.01,P<0.05),the positive expressions of C3,C3aR and CFB in renal tissues decreased(P<0.01).Conclusion Mahuang Lianqiao Chixiaodou Decoction can inhibit the inflammatory response and improve renal pathological damage in IgA nephropathy rats,and the mechanism may be related to the inhibition of alternative pathway complement activation and the regulation of C3a/C3aR and TLR4/NF-κB signaling pathways.

The American College of Gastroenterology Guidelines:Management of Acute Pancreatitis(referred to as the"2024 guidelines"),released in March 2024,presents 11 recommendations and 23 key concepts for the management of acute pancreatitis(AP)based on different levels of evidence quality.The 2024 guidelines provide detailed explanations regarding the diagnostic criteria,etiology,initial assessment,severity stratification,initial management,endoscopic retrograde cholangiopancreatography,antibiotic use,nutritional support,and surgical interventions for AP.Compared to the 2023 edition of the American College of Gastroenterology Guidelines,the 2024 edition offers more detailed recommendations and comprehensive evidence-based medical data,which is of great significance in optimizing the diagnosis and treatment process for AP patients and improving patient outcomes.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.