Objective     To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. Methods    The patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results     A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion     The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.

Objective:To investigate the application of endoscopic ultrasound-guided liver biopsy (EUS-LB) to liver transplant recipients.Methods:In this retrospective cohort study, a total of 12 liver transplant recipients who underwent EUS-LB by the same endoscopist and specimens were diagnosed and reported by the same pathologist due to abnormal liver function or need to be evaluated for graft fibrosis in the Organ Transplantation Center of the Affiliated Hospital of Qingdao University were enrolled into the EUS-LB group from December 2021 to March 2022, meanwhile, a total of 23 patients whose PLB was completed by the same hepatologist and specimens were diagnosed by the same pathologist during the same period were enrolled in the PLB group. Acquisition of liver specimens and postoperative adverse events of the two groups were compared.Results:Patients in both groups were punctured 1-2 times on average, and the median total length of liver specimens in the EUS-LB group was significantly longer than that in the PLB group (61 mm VS 17 mm, Z=11.362, P=0.002). There was no significant difference in the length of the longest liver specimens between the two groups (17.6±6.9 mm VS 13.7±3.5 mm, t=2.382, P=0.086), while the number of liver specimens in the EUS-LB group was more than that in the PLB group (4.8±2.1 VS 2.3±1.2, t=9.271, P=0.001). The number of complete portal tracts was 11.3±4.6 in the EUS-LB group and 6.2±3.3 in the PLB group ( t=8.457, P=0.003). Abdominal pain was the only postoperative adverse event, and only 1 patient in the EUS-LB group had postoperative abdominal pain, which was fewer than that in the PLB group [8.3% (1/12) VS 43.5% (10/23), χ2=4.893, P=0.036]. Conclusion:Compared with PLB, EUS-LB delivers longer liver biopsy specimens with more complete portal tracts in liver transplant recipients, and fewer recipients complain about postoperative pain in EUS-LB group. Therefore, EUS-LB is a safer, more effective and more comfortable liver biopsy method.

Objective To investigate T cell subtypes and their functions in liver immune microenvironments among patients with alveolar echinococcosis (AE) using single-cell RNA sequencing (scRNA-seq). Methods Four AE patients that were admitted to Qinghai Provincial People’s Hospital in 2023 for hepatic surgery for the first time were enrolled, and liver specimens were sampled 1 cm (peri-lesion, PL group) and > 5 cm from AE lesions (distal lesion, DL group) among each patient. Finally, a total of eight liver specimens were sampled from four AE patients for scRNA-seq analysis. Genome and transcriptome data of liver specimens were processed using the software Cell Ranger and R package. Differentially expressed genes (DEGs) and their biological functions were analyzed using gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the primary intercellular communication patterns and interaction mechanisms were identified among T cell subtypes in liver specimens using the CellChat package. In addition, the developmental stages of T cells were subjected to trajectory analysis with the monocle package to investigate the expression of genes associated with cell growth and tumor transformation, and to predict the developmental trajectories of T cells. Results All four AE patients were female, with a mean age of (25.00 ± 9.06) years, and there were three cases from Jiuzhi County, Golog Tibetan Autonomous Prefecture and one case from Chengduo County, Yushu Tibetan Autonomous Prefecture, Qinghai Province. The viability of single-cell samples from eight liver specimens was 90.41% to 96.33%, and a total of 81 763 cells were analyzed, with 19 cell types annotated. Of these cell types, 13 were immune cells (87.60%), and T cells (33.13%), neutrophils (15.40%), and natural killer cells (11.92%) were the three most common cell types. Re-clustering of 27 752 T cells and proliferative T cells identified 10 distinct T cell subtypes, with CD8⁺ cytotoxic T cells (23.43%), CD8⁺ naive T cells (12.80%), and CD4⁺ effector memory T cells (17.73%) as dominant cell types. The proportions of T helper 2 (Th2) cells (5.19% vs. 3.63%; χ² = 38.35, P < 0.01) and CD4⁺ effector memory T cells (21.59% vs. 13.67%; χ² = 244.70, P < 0.01) were significantly higher in liver specimens in the PL group than in the DL group, and the proportion of CD4⁺ helper T cells was significantly lower in the PL group than in the DL group (7.50% vs. 14.75%; χ² = 330.52, P < 0.01). KEGG pathway analysis revealed that Th2 cells were significantly enriched in cell apoptosis and multiple cancer-associated pathways, and CD4⁺ effector memory T cells were significantly enriched in the regulation of cytokines and chronic inflammation, while CD4⁺ helper T cells were significantly enriched in immune responses regulation. Trajectory analysis of T cells showed that CD4⁺ helper T cells were at an earlier developmental stage relative to Th2 cells and CD4⁺ effector memory T cells, and the expression of inhibitor of DNA binding 3 (ID3), thioredoxin interacting protein (TXNIP), Bcl2-associated athanogene 3 (BAG3) and heat shock protein family B (small) member 1 (HSPB1) genes appeared a tendency towards a decline over time. Conclusions CD4⁺ effector memory T cells and CD8⁺ cytotoxic T cells are primary interacting cells in the liver specimens of AE patients. Reduced expression of Th2 cells and CD4⁺ helper T cells contributes to an inhibitory immune microenvironment, which promotes immune evasion by Echinococcus multilocularis, and Th2 cells are significantly enriched in multiple cancer-associated pathways, which may be linked to the invasive growth of E. multilocularis.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To analyze the efficacy and safety of flumatinib,a second-generation tyrosine kinase inhibitor(TKI)independently developed in China,in patients with chronic myelogenous leukemia in chronic phase(CML-CP)who falied first-line and second-line treatment.Methods:The clinical data of 30 CML-CP patients treated with flumatinib in Lianyungang First People's Hospital from January 2020 to September 2022 were collected retrospectively.Among them,15 patients who received imatinib first-line treatment but failed treatment were included in the second-line group,and the other 15 patients who failed second-line treatment with nilotinib or dasatinib were included in the third-line group.The hematological and molecular responses of the patients in the two groups at 3,6 and 12 months of treatment,and the event-free survival(EFS)and adverse reactions of patients at the end of follow-up were statistical analyzed.Results:At 3,6,and 12 months of treatment,10,11,and 12 patients in the second line group achieved major molecular response(MMR),which was higher than that of 3,4,and 5 patients in the third line group(P=0.010,P=0.011,P=0.010).At 3 months of treatment,12 and 13 patients achieved complete hematological response(CHR)and early molecular response(EMR)in the second-line group,which was higher than that of 9 and 13 patients in the third-line group,but the difference between the two groups was not statistically significant(P=0.232,P=1.000);At 6 and 12 months of treatment,6 and 7 patients in the second-line group achieved MR4.5,which were higher than of 3 and 2 cases in the third-line group,but the difference was not statistically significant(P=0.427,P=0.713).The hematological adverse reactions of patients in the second-line group during treatment the period were mainly grade 1-2 thrombocytopenia and anemia,and no grade 3-4 of adverse reactions occurred.In the third-line group,there were 2 cases of grade 1-2 thrombocytopenia,grade 1-2 anemia and white blood cell 3 cases were reduced each,1 case of grade 3-4 anemia,2 cases of grade 3-4 neutropenia.The non-hematological adverse reactions in the second-line group were rash(2 cases),headache(1 case),diarrhea(1 case),fatigue(1 case),limb pain(1 case).There were 1 cases of diarrhea,1 cases of nausea,and 1 cases of edema in the third-line group.There was no statistical significance in hematological and non-hematological adverse reactions between the two groups of patients(P＞0.05).At the end of follow-up,the EFS rate of patients in the second-line group was higher than that in the third-line group(100％vs 93.3％),but the difference was not statistically significant(P=0.317).Conclusion:The second-generation TKI flumatinib independently developed in China,has good curative effect and safety for CML-CP patients who failed first-line and second-line treatment.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.