Objective To develop a system for retrieving information from clinical records of Traditional Chinese Medicine(TCM)based on generative large language models(LLMs).Methods Applicational needs of the system were analyzed,and entity types to be retrieved were identified.The functions,workflows,and architecture of the system were designed by combining the automatic retrieval capabilities of LLMs with human-in-the-loop(HITL).The software was developed using such frameworks as vLLM and Node.js.Interaction of multiple commercial/open source LLMs was implemented using OpenAI-compatible interfaces.The quality of information retrieved from LLMs was enhanced by prompt engineering.Results This system supported task allocation,automatic retrieval of structured information,and manual review.To evaluate its performance,the moonshot-v1-8k model was used to retrieve clinical records of TCM before manual edition was performed.Combining large language model pre-annotation with meticulous annotator edits improved accuracy by 26.6％compared to the BERT-BiLSTM-CRF model,and enhanced extraction efficiency by 1.6-fold relative to purely manual methods.Conclusion General generative LLMs can retrieve a wide range of entity information from TCM records with high accuracy and scalability.The design and implementation of this system approach may provide a useful reference for developing other biomedical information retrieval systems.

Objective: To predict and screen potential biomarkers of systemic lupus eythematosus(SLE) based on machine learning algorithms and structural biology, and to reveal their mechanisms of action and to provide new targets for disease diagnosis and treatment. Methods: Four machine learning algorithms, random forest(RF), eXtreme gradient boosting(XGBoost), support vector machine(SVM), least absolute shrinkage and selection operator(LASSO), were used to analyze the gene expression data of SLE patients in GEO(datasets: GSE121239 and GSE11907) to analyze the gene expression data of SLE patients and screen key markers. Peripheral blood single nucleated cells(PBMCs) from SLE patients were collected and RT-qPCR was used to detect differential gene expression levels. Subsequently, GSEA enrichment analysis was used to identify biomarker-related pathways. CIBERSORT immune infiltration analysis and protein interactions network were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Interaction relationships in combination with AlphaFold3(AF3) were predicted. Results: Multiple algorithms were screened together to identify the unique marker gene HERC5 , and expression analysis of multiple datasets showed that HERC5 was highly expressed in SLE compared to the normal group (P < 0. 05) , and RT⁃qPCR verified the same trend (P = 0. 006 2) . Functional enrichment analysis identified the major pathway promoted by HERC5 in SLE as the interferon receptor signalling pathway (P < 0. 05) . Immune infiltration analysis showed that HERC5 was closely associated with immune cells (Neutrophils : r = 0. 39 , P < 0. 05 ; Memory B cells : r = 0. 33 , P < 0. 05 ; Activated dendritic cell : r = 0. 52 , P < 0. 05) . Most HERC5 ⁃related interacting proteins were associated with SLE ,and potential transcription factors of HERC5 and its related genes were also significantly associated with immune responses. Conclusion The HERC5 gene is an important biomarker for SLE , which upregulates the interferon pathway to promote SLE progression and provides a new target for SLE diagnosis and treatment.

Objective:To explore the differences in bacterial communities within tissues during the process of oral mucosal carcinogenesis, and analyze the relationship between the high-abundance species Prevotella intermedia (Pi) and the occurrence and development of oral mucosal carcinogenesis. Methods:Fresh tissue samples were collected from patients diagnosed with oral leukoplakia (OLK), oral squamous cell carcinoma (OSCC), and healthy controls (HC) at Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, from January 2022 to November 2024, following strict inclusion criteria. Bacterial DNA was extracted from these specimens, and the 2bRAD sequencing for microbiome (2bRAD-M) was employed to analyze and compare the α and β diversity, as well as the community composition of bacteria within tissues, aiming to identify specifically expressed bacteria. Subsequently, paraffin-embedded clinical specimens were collected: 15 cases in the OLK group (including 4 cases of simple hyperplasia, 6 cases of mild dysplasia, and 5 cases of moderate to severe dysplasia), 12 cases in the OSCC group, and 5 cases in the HC group. A 4-nitroquinoline N-oxide (4NQO)-induced OLK progression mouse model was also constructed. Mice were randomly divided into three groups using a random number table, with six in each group. The negative control group was given distilled water to drink; Group 1 was given distilled water containing 4NQO to drink until week 12, while Group 2 was given distilled water containing 4NQO to drink until week 22. After the mice were sacrificed, their tongue tissue were collected and fixed. Fluorescence in situ hybridization (FISH) with specific probes was used to validate the presence of Pi in human and mouse tissue sections, analyzing the correlation between histopathological grading and the invasion depth of Pi.Results:The 2bRAD-M microbial analysis revealed that the relative abundance of Pi in OSCC tissues (10.80%) was significantly higher than in the HC group (0.50%) ( P=0.001) and OLK group (0.70%) ( P=0.002). FISH probe detection showed that the fluorescence intensity of Pi in human OSCC tissues [123.50 (101.00, 142.30)] was higher than in the HC group [0.00 (0.00, 28.50)], simple hyperplasia OLK [0.00 (0.00, 35.25)], and mild dysplasia OLK [24.50 (0.00, 55.50)] groups, with statistically significant differences respectively ( P=0.002, P=0.003, P=0.005). However, there was no significant difference compared to moderate to severe dysplasia OLK [56.00 (28.00, 62.50)] ( P=0.210). The fluorescence area of Pi in human OSCC tissues [8 615.00 (7 439.00, 11 084.00)] was significantly larger than in the HC group [0.00 (0. 00, 45.00)], simple hyperplasia OLK group [0.00 (0.00, 81.00)], mild dysplasia [49.00 (0.00, 151.00)], and moderate to severe dysplasia groups [1 450.00 (454.00, 2 892.00)], with highly significant differences ( P<0.001). There was a significant correlation between the invasive depth of Pi and the degree of histopathological grading ( P<0.001). In mice, the fluorescence intensity of Pi in OSCC tissues [120.00 (110.00, 127.00)] was significantly higher than in the HC group [0.00 (0.00, 12.25)] ( P<0.01), but showed no significant difference compared with the OLK group [50.00 (0.00, 58.00)] ( P>0.05). The fluorescence area of Pi in mice OSCC tissues [11 020.00 (6 790.00, 12 102.00)] was significantly larger than in the HC group [0.00 (0.00, 56.75)] and the OLK group [0.00 (0.00, 751.50)] ( P=0.006, P=0.043). There is a significant correlation between the depth of invasion of Pi and the degree of histopathological grading ( P<0.01). Conclusions:This study suggests that Pi in oral mucosal tissue may be a potential biomarker for early detection of OSCC and play an important role in the carcinogenesis process of oral mucosa.

Objective To investigate the predictive value of serum interleukin-17(IL-17)and soluble hemoglobin scavenger receptor 163(sCD163)for early anastomotic leakage in patients with colorectal cancer after laparoscopic surgery.Methods From June 2022 to June 2024,80 colorectal cancer patients who underwent laparoscopic surgery were selected as the study subjects.Patients were subdivided into an anastomotic leakage group(17 cases)and a non-anastomotic leakage group(63 cases)according to whether an anastomotic leakage occurred within 7 d postoperatively.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of serum IL-17 and sCD163 in patients on preoperative day 1,postoperative day 1,postoperative day 3,postoperative day 5,and postoperative day 7.The clinical data of the two groups were compared.Multivariate Logistic regression was applied to analyze the influencing factors of early anastomotic leakage in colorectal cancer patients after laparoscopic surgery.The receiver operating characteristic curve(ROC curve)was applied to analyze the predictive value of serum IL-17 and sCD163 levels for early anastomotic leakage in colorectal cancer patients after laparoscopic surgery.Results The percentage of distance between tumor and anus＜7 cm was higher in the anastomotic leakage group than that in the non-anastomotic leakage group,and the amount of drainage was more than that in the non-anastomotic leakage group at 7 d postoperatively,the differences were statistically significant(P＜0.05).There were statistically significant differences in the levels of serum IL-17 and sCD163 between the two groups of patients at different time points,as well as in time and interaction effects(P＜0.05).Distance between tumor and anus＜7 cm(O R=3.176,95％CI:1.128～8.940),serum IL-17 level ≥ 43.95 pg/mL at 3 d postoperatively(O R=2.145,95％CI:1.281～3.592),and serum sCD163 level ≥ 81.02 pg/mL at 5d postoperatively(OR=1.852,95％CI:1.225～2.801)were the risk factors of early anastomotic leakage in patients with colorectal cancer after laparoscopic surgery(P＜0.05).The area under the curve(AUC)of the combination of serum IL-17 and sCD163 in predicting early anastomotic leakage in colorectal cancer patients after laparoscopic surgery was 0.923,which was superior to the single diagnosis of serum IL-17 and sCD163(Zcombination-IL-17=2.77,Zcombination-sCD163=2.11,P＜0.05).Conclusion Serum IL-17 and sCD163 levels are elevated in colorectal cancer patients with early anastomotic leakage after laparoscopic surgery.The combined detection of the two has certain clinical value in predicting early anastomotic leakage in patients with colorectal cancer after laparoscopic surgery.

Objective:To explore the differences in bacterial communities within tissues during the process of oral mucosal carcinogenesis, and analyze the relationship between the high-abundance species Prevotella intermedia (Pi) and the occurrence and development of oral mucosal carcinogenesis. Methods:Fresh tissue samples were collected from patients diagnosed with oral leukoplakia (OLK), oral squamous cell carcinoma (OSCC), and healthy controls (HC) at Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, from January 2022 to November 2024, following strict inclusion criteria. Bacterial DNA was extracted from these specimens, and the 2bRAD sequencing for microbiome (2bRAD-M) was employed to analyze and compare the α and β diversity, as well as the community composition of bacteria within tissues, aiming to identify specifically expressed bacteria. Subsequently, paraffin-embedded clinical specimens were collected: 15 cases in the OLK group (including 4 cases of simple hyperplasia, 6 cases of mild dysplasia, and 5 cases of moderate to severe dysplasia), 12 cases in the OSCC group, and 5 cases in the HC group. A 4-nitroquinoline N-oxide (4NQO)-induced OLK progression mouse model was also constructed. Mice were randomly divided into three groups using a random number table, with six in each group. The negative control group was given distilled water to drink; Group 1 was given distilled water containing 4NQO to drink until week 12, while Group 2 was given distilled water containing 4NQO to drink until week 22. After the mice were sacrificed, their tongue tissue were collected and fixed. Fluorescence in situ hybridization (FISH) with specific probes was used to validate the presence of Pi in human and mouse tissue sections, analyzing the correlation between histopathological grading and the invasion depth of Pi.Results:The 2bRAD-M microbial analysis revealed that the relative abundance of Pi in OSCC tissues (10.80%) was significantly higher than in the HC group (0.50%) ( P=0.001) and OLK group (0.70%) ( P=0.002). FISH probe detection showed that the fluorescence intensity of Pi in human OSCC tissues [123.50 (101.00, 142.30)] was higher than in the HC group [0.00 (0.00, 28.50)], simple hyperplasia OLK [0.00 (0.00, 35.25)], and mild dysplasia OLK [24.50 (0.00, 55.50)] groups, with statistically significant differences respectively ( P=0.002, P=0.003, P=0.005). However, there was no significant difference compared to moderate to severe dysplasia OLK [56.00 (28.00, 62.50)] ( P=0.210). The fluorescence area of Pi in human OSCC tissues [8 615.00 (7 439.00, 11 084.00)] was significantly larger than in the HC group [0.00 (0. 00, 45.00)], simple hyperplasia OLK group [0.00 (0.00, 81.00)], mild dysplasia [49.00 (0.00, 151.00)], and moderate to severe dysplasia groups [1 450.00 (454.00, 2 892.00)], with highly significant differences ( P<0.001). There was a significant correlation between the invasive depth of Pi and the degree of histopathological grading ( P<0.001). In mice, the fluorescence intensity of Pi in OSCC tissues [120.00 (110.00, 127.00)] was significantly higher than in the HC group [0.00 (0.00, 12.25)] ( P<0.01), but showed no significant difference compared with the OLK group [50.00 (0.00, 58.00)] ( P>0.05). The fluorescence area of Pi in mice OSCC tissues [11 020.00 (6 790.00, 12 102.00)] was significantly larger than in the HC group [0.00 (0.00, 56.75)] and the OLK group [0.00 (0.00, 751.50)] ( P=0.006, P=0.043). There is a significant correlation between the depth of invasion of Pi and the degree of histopathological grading ( P<0.01). Conclusions:This study suggests that Pi in oral mucosal tissue may be a potential biomarker for early detection of OSCC and play an important role in the carcinogenesis process of oral mucosa.

OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

Objective To investigate the predictive value of serum interleukin-17(IL-17)and soluble hemoglobin scavenger receptor 163(sCD163)for early anastomotic leakage in patients with colorectal cancer after laparoscopic surgery.Methods From June 2022 to June 2024,80 colorectal cancer patients who underwent laparoscopic surgery were selected as the study subjects.Patients were subdivided into an anastomotic leakage group(17 cases)and a non-anastomotic leakage group(63 cases)according to whether an anastomotic leakage occurred within 7 d postoperatively.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of serum IL-17 and sCD163 in patients on preoperative day 1,postoperative day 1,postoperative day 3,postoperative day 5,and postoperative day 7.The clinical data of the two groups were compared.Multivariate Logistic regression was applied to analyze the influencing factors of early anastomotic leakage in colorectal cancer patients after laparoscopic surgery.The receiver operating characteristic curve(ROC curve)was applied to analyze the predictive value of serum IL-17 and sCD163 levels for early anastomotic leakage in colorectal cancer patients after laparoscopic surgery.Results The percentage of distance between tumor and anus＜7 cm was higher in the anastomotic leakage group than that in the non-anastomotic leakage group,and the amount of drainage was more than that in the non-anastomotic leakage group at 7 d postoperatively,the differences were statistically significant(P＜0.05).There were statistically significant differences in the levels of serum IL-17 and sCD163 between the two groups of patients at different time points,as well as in time and interaction effects(P＜0.05).Distance between tumor and anus＜7 cm(O R=3.176,95％CI:1.128～8.940),serum IL-17 level ≥ 43.95 pg/mL at 3 d postoperatively(O R=2.145,95％CI:1.281～3.592),and serum sCD163 level ≥ 81.02 pg/mL at 5d postoperatively(OR=1.852,95％CI:1.225～2.801)were the risk factors of early anastomotic leakage in patients with colorectal cancer after laparoscopic surgery(P＜0.05).The area under the curve(AUC)of the combination of serum IL-17 and sCD163 in predicting early anastomotic leakage in colorectal cancer patients after laparoscopic surgery was 0.923,which was superior to the single diagnosis of serum IL-17 and sCD163(Zcombination-IL-17=2.77,Zcombination-sCD163=2.11,P＜0.05).Conclusion Serum IL-17 and sCD163 levels are elevated in colorectal cancer patients with early anastomotic leakage after laparoscopic surgery.The combined detection of the two has certain clinical value in predicting early anastomotic leakage in patients with colorectal cancer after laparoscopic surgery.

Metal-organic complexes have a long history of clinical application and have shown remarkable efficacy in the treatment of hypertension,skin infections and gastrointestinal diseases.In recent years,the application of metalloids in anti-bacterial infection thera-py and their mechanism of action have been widely studied.In this paper,three commonly used metallodrugs are selected as examples to review the progress and mechanism of metalloids in antibacterial applications,the research of novel metal-based drugs and the metallo-drugs with extracted components of traditional Chinese medicines and their derivatives,and to analyze the potential advantages of metallo-drugs in the field of antibacterial.

The major histocompatibility complex(MHC)is closely related to immune regulation.MHC shows distinct genetic polymorphism,and there are also species differences in MHC restriction.The human MHC is called human leukocyte antigen(HLA),and the mouse MHC is called H-2.The construction of humanized MHC transgenic mouse models is an important strategy to overcome the differences in MHC among species and simulate the characteristics of a human immune response.MHC transgenic mice are mainly divided into MHC Ⅰ or MHC Ⅱ single-transgenic mouse models and MHC Ⅰ and MHC Ⅱ double-transgenic mouse models.The development of HLA Ⅰ transgenic mouse model went through three stages,at present,the strategy of knocking out H-2Kb and H-2Db or murine β2m is adopted to eliminate the competitive inhibition of HLA Ⅰ molecules by endogenous H-2 class Ⅰ molecules.In the construction of an HLA Ⅱtransgenic mouse model,the β strand of murine origin is knocked out and HLA Ⅱ class genes are inserted.With the optimization of construction strategies,MHC transgenic mouse models have been applied to epitope vaccine development,tumor treatment,and genetic disease-association studies,becoming a powerful tool for preclinical trials.In this paper,we summarize the relevant data on MHC transgenic mouse models,as well as the construction strategies used for MHC transgenic mouse models and their application in vaccine development and disease treatment.

Objective:To discuss the clinical manifestations and laboratory examination results of agranulocytosis and reactive plasmacytosis(RP)in the patient with Graves'disease(GD)after treated with methimazole(MMI),and to provide the basis for the clinicians to differentiate RP from multiple myeloma(MM).Methods:The clinical manifestations,laboratory examinations,diagnosis and treatment processes of one patient with GD agranulocytosis complicated with RP were analyzed,and the related literatures were reviewed.Results:The patient had a history of GD and abdominal infection.Upon admission,a complete blood count revealed a significant decrease in white blood cell count accompanied by neutropenia,and a smear re-examination showed suspicious plasma cells.The bone marrow cytology examination results showed the percentage of bone marrow plasma cells was 33％,and the percentage of plasma cells in peripheral blood was 4％;the serum immunoglobulin results showed polyclonal hyperplasia;the serum immunofixation electrophoresis results were negative;the flow cytometry analysis results indicated the immunophenotype of the plasma cells was normal.Based on the medical history and laboratory results,MM was largely excluded,supporting the diagnosis of RP.Neutropenia was considered to be related to medication,so MMI was discontinued,granulocyte colony-stimulating factor was administered to increase the number of white blood cells,and specialized GD treatment was conducted after controlling the abdominal infection.The patient had a good prognosis,and his blood count was normal upon re-examination 6 months later.Conclusion:Agranulocytosis complicated with RP in the GD patients is clinically rare.Serum immunofixation electrophoresis,blood cell morphology,and cell immunophenotype analysis are helpful for the accurate diagnosis.After actively treating the primary disease causing RP,the patient's prognosis is favorable.