Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Objective To identify the core constitutions and prodromal symptoms of relapse in schizophrenia patients using network analysis,and to analyze their relationships as well as gender differences.Methods Schizophrenia patients hospitalized in the psychiatry department of Hunan Brain Hospital in Hunan Province between October 2022 and December 2023 were selected as survey participants.A general information questionnaire,a Traditional Chinese Medicine Constitution Scale,and a Schizophrenia Prodromal Symptoms of Relapse Scale were used for investigation.Network anal-ysis was conducted using R language.Results The core constitutions of schizophrenia patients were qi deficiency constitution[Expected Influence(EI)=1.08]and dampness-heat constitution(EI=1.00),and the core prodromal symptoms of relapse were depression/withdrawal(EI=0.84)and ini-tial psychotic manifestations(EI=0.81).There were statistically significant differences in constitutions of traditional Chinese medicine and prodromal symptoms of relapse between patients of different genders(P＜0.05).Females mainly exhibited qi deficiency constitution(EI=1.20)with anxiety as the core prodromal symptom(EI=0.98),while males mainly exhibited yin deficiency constitution(EI=1.05)with depression/withdrawal as the core prodromal symptom(EI=1.00).Conclusion Healthcare professionals can early identify core prodromal symptoms of relapse by core imbalanced constitutions of schizophrenia patients,and develop precise intervention strategies,thereby promoting changes in their network structure,preventing disease relapse,and improving patients'quality of life.

Objective:To construct and validate a predictive model for postoperative pulmonary complications (PPCs) in patients undergoing robot-assisted laparoscopic urological surgery.Methods:This retrospective study included the medical records of 932 patients who underwent robot-assisted laparoscopic urological surgery at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2020 to February 2022. The patients were divided into a training group ( n=559) and a validation group ( n=373) at a 6∶4 ratio. Logistic regression analysis was used to determine the independent risk factors for PPCs, and a nomogram prediction model was constructed based on these factors. The performance of the model was evaluated using the receiver operating characteristic curve and calibration curve, and the clinical benefit was assessed using the clinical decision curve analysis. Results:The independent risk factors for PPCs included advanced age (>60 yr), smoking history, respiratory tract infection within 1 month, preoperative low SpO 2 (<96%), and prolonged length of postoperative hospital stay ( P<0.05), and the body mass index (18.5-<28.0 kg/m 2) was a protective factor. The nomogram prediction model developed based on the aforementioned 6 influencing factors had an area under the receiver operating characteristic curve of 0.81 (95% confidence interval 0.76-0.86) in training group and 0.80 (95% confidence interval 0.75-0.86) in validation group. The calibration curve indicated a good consistency between the predicted and actual occurrence curves, and the clinical decision curve analysis showed good accuracy and net benefit of the prediction model. Conclusions:The predictive model for PPCs is successfully constructed based on age, low body mass index, smoking history, history of respiratory tract infection within 1 month, preoperative low SpO 2 and prolonged length of postoperative hospital stay and has good predictive performance in patients undergoing robot-assisted laparoscopic urological surgery.

Objective:To construct and validate a predictive model for postoperative pulmonary complications (PPCs) in patients undergoing robot-assisted laparoscopic urological surgery.Methods:This retrospective study included the medical records of 932 patients who underwent robot-assisted laparoscopic urological surgery at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2020 to February 2022. The patients were divided into a training group ( n=559) and a validation group ( n=373) at a 6∶4 ratio. Logistic regression analysis was used to determine the independent risk factors for PPCs, and a nomogram prediction model was constructed based on these factors. The performance of the model was evaluated using the receiver operating characteristic curve and calibration curve, and the clinical benefit was assessed using the clinical decision curve analysis. Results:The independent risk factors for PPCs included advanced age (>60 yr), smoking history, respiratory tract infection within 1 month, preoperative low SpO 2 (<96%), and prolonged length of postoperative hospital stay ( P<0.05), and the body mass index (18.5-<28.0 kg/m 2) was a protective factor. The nomogram prediction model developed based on the aforementioned 6 influencing factors had an area under the receiver operating characteristic curve of 0.81 (95% confidence interval 0.76-0.86) in training group and 0.80 (95% confidence interval 0.75-0.86) in validation group. The calibration curve indicated a good consistency between the predicted and actual occurrence curves, and the clinical decision curve analysis showed good accuracy and net benefit of the prediction model. Conclusions:The predictive model for PPCs is successfully constructed based on age, low body mass index, smoking history, history of respiratory tract infection within 1 month, preoperative low SpO 2 and prolonged length of postoperative hospital stay and has good predictive performance in patients undergoing robot-assisted laparoscopic urological surgery.

Objective:To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification.Methods:Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC).Results:A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m 2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95% CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions:There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.

Objective:To evaluate the effect of dexmedetomidine on the blood concentrations of ropivacaine during sciatic nerve block in rabbits.Methods:Twelve New Zealand rabbits of both sexes, weighing 2-3 kg, were randomly divided into ropivacaine group (R group) and ropivacaine mixed with dexmedetomidine group (RD group). The right femoral vein was cannulated for blood sampling in both groups, 0.375% ropivacaine 3 ml was injected around the left sciatic nerve in group R, and 0.375% ropivacaine 3 ml containing 1.5 μg/kg dexmedetomidine was injected instead in group RD.Blood samples from the right femoral vein were collected before nerve block (T 0) and at 15, 30, 45, 60, 120 and 180 min after nerve block (T 1-6) for determination of plasma concentrations of ropivacaine using high-performance liquid chromatography after centrifugation, and concentration-time curves were plotted. Results:Compared with group R, the blood concentrations of ropivacaine were significantly decreased at T 1-3 ( P<0.05), no significant change was found in the blood concentrations of ropivacaine at T 4-6 ( P>0.05), the peak blood concentration of ropivacaine was significantly decreased ( P<0.01), and no significant change was found in the time to peak blood concentrations of ropivacaine or area under the concentration-time curves in group RD ( P>0.05). Conclusions:Dexmedetomidine can decrease the blood concentrations of ropivacaine during sciatic nerve block in rabbits.

Objective:To explore the genetic basis for a patient with factor XIII (FXIII) deficiency.Methods:All exons of the F13A1 and F13B genes were amplified by PCR and sequenced directly. The sequencing was performed with a reverse primer if a variant was found. Conservation of variant site was analyzed by the ClustalX software. Four online bioinformatic software including MutationTaster, PolyPhen-2, PROVEAN and SIFT were used to predict the function of the mutation site. The Swiss-PdbViewer software was applied to analyze the changes in the protein model and intermolecular force. Results:The proband was found to harbor a novel c. 515G>C (p.Arg171Pro) variant of the F13A1 gene. The corresponding amino acid Arg171 is conserved among homologous species. Bioinformatic analysis indicated that Arg171Pro variant may affect the protein function. Protein model analysis showed that in the wild-type, there is one hydrogen bond between Arg171 and Pro27; one hydrogen bond between Arg171 and Thr28; two hydrogen bonds between Arg171 and Glu102. When Arg171 was mutated to Pro171, the three hydrogen bonds between Arg171 and Pro27, Glu102 are all disappeared and formed a new benzene ring which might affect the stability of the protein structure. No variant was found in the F13B gene. Conclusion:The Arg171Pro variant may account for the decreased FXIII level. Above finding has enriched the spectrum of F13A1 gene variants.

Objective    We conducted a questionnaire study who attended the First West China Forum on Chest Enhanced Recovery after Surgery (ERAS) in order to analyze whether it can improve the knowledge of ERAS and how to organize an effective meeting. Methods    We analyzed 188 questionnaires from the representatives of the First West China Forum on Chest ERAS after the meeting which included two parts: one was the personal basic information and institution of respondents, and the other was the opinion of the content setting and suggestion for the next forum. Results     A percentage of 97.7% of participants believed that this forum contributed to improving their understanding of ERAS and 65.3% of them will put the concept of ERAS into practice after the meeting. The exchange of experience and project communication of ERAS were the most useful agendas approved by representatives while expert lectures should be more appropriate (18.1%). Arrangement for topic discussion and enough time for discussion were supported by 93.1%and 98.9% of the representatives respectively. Multi-center project discussion (80.9%) and interactive sessions especially WeChat interaction (74.0%) should be added on ERAS forum. Conclusion    Reasonable agenda settings are beneficial to improve the understanding and compliance of application of ERAS.