ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

Sepsis is a life-threatening organ dysfunction caused by dysfunctional response to infection.Its key pathogenic links include immune damage and target organ involvement，which is a major cause of death in critically ill children.O-linked N-acetylglucosamine（O-GlcNAc）glycosylation，an important post-translational modification of proteins，influences various biological processes，including glucose metabolism，immune inflammatory response，and ferroptosis，by modifying specific proteins，thereby playing a role in the onset and progression of sepsis.Research indicates that O-GlcNAcylation has an important protective effect against organ injuries in the heart，brain，lungs，liver，and intestines during sepsis.However，the impact of this modification can vary depending on the target proteins and the cellular environment.From both the domestic and international perspective，this paper reviews the advances in O-GlcNAcylation in the pathogenesis of septic organ injury，aiming to offer new insights and strategies for the clinical management of sepsis.

Objective To investigate the expression and significance of 25-hydroxyvitamin D[25(OH)D],immune cell subsets,and helper T cell(Th)1 and Th2 in patients with unexplained recurrent spontaneous abortion(URSA).Methods A total of 307 URSA patients were enrolled as URSA group,which was further divided into non-maintenance of pregnancy group(n=127)and ma-intenance of pregnancy group(n=180)based on pregnancy maintenance status.Another 307 healthy pregnant women in the same period were selected as control group.The levels of 25(OH)D,immune cell subsets,and Th1/Th2 expression were compared among these groups.Pearson correlation analy-sis was used to explore the correlations of 25(OH)D and immune cell subsets with Th1/Th2 expres-sion in URSA patients.Results Compared with the control group,the URSA group had significantly lower levels of 25(OH)D and interleukin-10(IL-10),and higher levels of CD3+,CD3+CD4+,CD3+CD8+,CD4+/CD8+,CD16+CD56+,CD19+,interleukin-2(IL-2),and tumor necrosis fac-tor-α(TNF-α)(P＜0.001).Compared with the maintenance of pregnancy group,the non-maintenance of pregnancy group had significantly lower levels of 25(OH)D and IL-10,and higher levels of CD3+,CD3+CD4+,CD3+CD8+,CD4+/CD8+,CD16+CD56+,CD19+,IL-2,and TNF-α(P＜0.001).Pearson analysis revealed that 25(OH)D in URSA patients was significantly negatively correlated with IL-2 and TNF-α(P＜0.05),while positively correlated with IL-10(P＜0.05).Immune cell sub-sets,including CD3+,CD3+CD4+,CD3+CD8+,CD4+/CD8+,CD16+CD56+,and CD19+were significantly positively correlated with IL-2 and TNF-α(P＜0.05),while negatively correlated with IL-10 in URSA patients(P＜0.05).Conclusion There are abnormalities in 25(OH)D,im-mune cell subsets,and Th1/Th2 cytokine expression in URSA patients,and these expressions differ in URSA patients with different pregnancy outcomes.The underlying mechanism may be related to the regulation of Th1/Th2 cytokine balance.

ObjectiveTo construct and validate a clinical prediction model for diabetic kidney disease （DKD） based on optical coherence tomography angiography （OCTA）. MethodsThis study enrolled 567 diabetes patients. The random forest algorithm as well as logistic regression analysis were applied to construct the prediction model. The model discrimination and clinical usefulness were evaluated by receiver operating characteristic curve （ROC） and decision curve analysis （DCA）， respectively. ResultsThe clinical prediction model for DKD based on OCTA was constructed with area under the curve （AUC） of 0.878 and Brier score of 0.11. ConclusionsThrough multidimensional verification， the clinical prediction nomogram model based on OCTA allowed for early warning and advanced intervention of DKD.

Objective:To investigate the clinical effect of super-thin free anterolateral thigh (ALT) flap at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defects of the foot.Methods:The clinical data of patients with foot soft tissue defects admitted to Northern Jiangsu People’s Hospital Affiliated to Yangzhou University from June 2017 to December 2022 were retrospectively analyzed. During the operation, the super-thin free ALT flap on the affected side was harvested at the junction of superficial and deep fat of superficial fascia to repair the foot wound. The donor site wound was sutured directly or repaired with full-thickness skin graft. The flap survival and complications were observed after the operation, and the operation effect was evaluated from the following five aspects. (1) The Maryland foot function score was used to evaluate the recovery of foot function. The full score was 100 points, of which 90-100 points were excellent, 75-89 points were good, 50-74 points were fair, and < 50 points were poor. (2) The Vancouver scar scale (VSS) was used to evaluate the scar condition of the foot. The total score was 0-15 points. The higher the score, the more serious the scar. (3) The cold intolerance symptom severity (CISS) scale was used to evaluate the cold tolerance of the affected foot. The total score was 4-100 points. The higher the score, the more serious the symptoms. (4) Measuring static two-point discrimination to evaluate foot sensation, the smaller the measured value, the better the sensory recovery. (5) The satisfaction of patients with foot appearance was investigated, which was divided into five grades: very satisfied, satisfied, general, dissatisfied and very dissatisfied. Descriptive analysis of the data was performed using SPSS 26.0 software.Results:A total of 13 patients with foot soft tissue defects were enrolled, including 8 males and 5 females. The mean age was 54.7 years (range, 39-70 years). There were 10 cases of left foot and 3 cases of right foot. The wound area after thorough debridement ranged from 5.5 cm ×5.0 cm to 22.0 cm ×18.0 cm. The operation time was (145.1 ± 30.6) min. The area of the flap was 6.0 cm×5.5 cm to 23.5 cm×19.0 cm, and the thickness was (5.2 ± 1.1) mm (range, 3.0- 6.5 mm). The wound at the donor site was sutured directly in 9 cases, and coverd with the abdominal full-thickness skin graft in 4 cases. After the operation, 1 patient had partial epidermal necrosis at the distal end of the flap, 1 patient had venous crisis.The flaps survived after symptomatic treatment. The remaining 11 flaps survived smoothly. The patients were followed up for 12 to 20 months, with an average of 16 months. The foot flaps were soft and free of damage, and no secondary fat reduction or plastic surgery was required. There were no complications such as wound dehiscence, skin graft necrosis, muscle hernia, and quadriceps weakness in 13 cases of donor site except for hypoesthesia caused by scar hyperplasia in 4 cases with skin graft. At the last follow-up, the Maryland foot function score was (87.4±7.3) points, of which 7 cases were excellent, 4 cases were good, and 2 cases were fair. The excellent and good rate was 11/13. The foot scar was not obvious, the VSS score was (3.2±1.2) points. The foot was more tolerant to cold and the sensory recovery was better, the CISS score was (37.5±7.1) points and the static two-point discrimination was (13.9±1.0) mm. One month after the operation, the results of patients’ satisfaction with foot appearance were as follows: 11 cases were very satisfied and 2 cases were satisfied.Conclusion:The super-thin free ALT flap is obtained at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defect of the foot, which can optimize the operation time. The appearance and function of the foot recover well after the operation, avoiding the secondary shaping operation, reducing the damage to the donor site, and the patients are satisfied.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Objective:To investigate the clinical effect of super-thin free anterolateral thigh (ALT) flap at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defects of the foot.Methods:The clinical data of patients with foot soft tissue defects admitted to Northern Jiangsu People’s Hospital Affiliated to Yangzhou University from June 2017 to December 2022 were retrospectively analyzed. During the operation, the super-thin free ALT flap on the affected side was harvested at the junction of superficial and deep fat of superficial fascia to repair the foot wound. The donor site wound was sutured directly or repaired with full-thickness skin graft. The flap survival and complications were observed after the operation, and the operation effect was evaluated from the following five aspects. (1) The Maryland foot function score was used to evaluate the recovery of foot function. The full score was 100 points, of which 90-100 points were excellent, 75-89 points were good, 50-74 points were fair, and < 50 points were poor. (2) The Vancouver scar scale (VSS) was used to evaluate the scar condition of the foot. The total score was 0-15 points. The higher the score, the more serious the scar. (3) The cold intolerance symptom severity (CISS) scale was used to evaluate the cold tolerance of the affected foot. The total score was 4-100 points. The higher the score, the more serious the symptoms. (4) Measuring static two-point discrimination to evaluate foot sensation, the smaller the measured value, the better the sensory recovery. (5) The satisfaction of patients with foot appearance was investigated, which was divided into five grades: very satisfied, satisfied, general, dissatisfied and very dissatisfied. Descriptive analysis of the data was performed using SPSS 26.0 software.Results:A total of 13 patients with foot soft tissue defects were enrolled, including 8 males and 5 females. The mean age was 54.7 years (range, 39-70 years). There were 10 cases of left foot and 3 cases of right foot. The wound area after thorough debridement ranged from 5.5 cm ×5.0 cm to 22.0 cm ×18.0 cm. The operation time was (145.1 ± 30.6) min. The area of the flap was 6.0 cm×5.5 cm to 23.5 cm×19.0 cm, and the thickness was (5.2 ± 1.1) mm (range, 3.0- 6.5 mm). The wound at the donor site was sutured directly in 9 cases, and coverd with the abdominal full-thickness skin graft in 4 cases. After the operation, 1 patient had partial epidermal necrosis at the distal end of the flap, 1 patient had venous crisis.The flaps survived after symptomatic treatment. The remaining 11 flaps survived smoothly. The patients were followed up for 12 to 20 months, with an average of 16 months. The foot flaps were soft and free of damage, and no secondary fat reduction or plastic surgery was required. There were no complications such as wound dehiscence, skin graft necrosis, muscle hernia, and quadriceps weakness in 13 cases of donor site except for hypoesthesia caused by scar hyperplasia in 4 cases with skin graft. At the last follow-up, the Maryland foot function score was (87.4±7.3) points, of which 7 cases were excellent, 4 cases were good, and 2 cases were fair. The excellent and good rate was 11/13. The foot scar was not obvious, the VSS score was (3.2±1.2) points. The foot was more tolerant to cold and the sensory recovery was better, the CISS score was (37.5±7.1) points and the static two-point discrimination was (13.9±1.0) mm. One month after the operation, the results of patients’ satisfaction with foot appearance were as follows: 11 cases were very satisfied and 2 cases were satisfied.Conclusion:The super-thin free ALT flap is obtained at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defect of the foot, which can optimize the operation time. The appearance and function of the foot recover well after the operation, avoiding the secondary shaping operation, reducing the damage to the donor site, and the patients are satisfied.

Islet transplantation is one of the effective therapies for diabetes mellitus. Nevertheless, multiple issues still exist, such as shortage of donors and adverse reactions caused by long-term use of immunosuppressants, which limit the islet survival post-transplantation. Microencapsulated islet transplantation may overcome these difficulties to certain extent, whereas many factors, such as the destruction of immune isolation microenvironment within the microcapsules and insufficient supply of oxygen and nutrients, constrain the application of microencapsulated islet transplantation in clinical practice. In recent years, how to enhance the effect of microencapsulated islet transplantation has been gradually studied. The application of stem cells in microencapsulated islet transplantation has steadily become a research hot spot. Therefore, the optimizing strategies for microencapsulated islet transplantation and the application of stem cells in microencapsulated islet transplantation were reviewed, and the potential improvement techniques of microencapsulated islet transplantation were investigated in this article, aiming to provide reference for further clinical application of microencapsulated islet transplantation.

Objective To investigate the effect of compound Fufangteng mixture-containing serum on the proliferation of bone marrow mesenchymal stem cell (BMSC) and its mechanism. Methods Rat BMSC were isolated, cultured and purified in vitro by direct adherence method. Cell morphology was observed. Surface markers were identified by flow cytometry. The rats were treated with compound Fufangteng mixture at a dose of 3 mL/(kg·d) by gavage for 14 d, and then the drug-containing serum was collected. BMSC were divided into the blank control group, drug-containing serum group, Notch1 small interfering ribonucleic acid (siRNA) group and Notch1 siRNA+drug-containing serum group. The proliferation rate of BMSC was detected and the relative expression levels of Notch1 signaling pathway-associated messenger ribonucleic acid (mRNA) and proteins were measured in each group. Results Microscopic observation showed that the first generation BMSC were seen in the long spindle shape, and grown in the parallel or spiral pattern. The third generation BMSC positively expressed CD90 and CD44, whereas were negative for CD45. Compared with the blank control group, the proliferation rate of BMSC in the drug-containing serum group and Notch1 siRNA+ drug-containing serum group was significantly increased, whereas that of BMSC was significantly decreased in the Notch1 siRNA group (all P < 0.05). Compared with the Notch1 siRNA group, the proliferation rate of BMSC was significantly increased in the Notch1 siRNA+drug-containing serum group (P < 0.05). Compared with the blank control group, the relative expression levels of Hey1 and Delta-like ligand (DLL)1 mRNA and proteins were significantly up-regulated in the drug-containing serum group, whereas those were significantly down-regulated in the Notch1 siRNA group and Notch1 siRNA+drug-containing serum group (all P < 0.05). Compared with the Notch1 siRNA group, the relative expression levels of Hey1 and DLL1 mRNA and proteins were significantly up-regulated in the Notch1 siRNA+drug-containing serum group (all P < 0.05). Conclusions Compound Fufangteng mixture-containing serum may promote the proliferation of rat BMSC, and its mechanism is probably associated with the activation of Notch1 signaling pathway.