Objective: To develop QingNangTCM, a specialized large language model (LLM) tailored for expert-level traditional Chinese medicine (TCM) question-answering and clinical reasoning, addressing the scarcity of domain-specific corpora and specialized alignment. Methods: We constructed QnTCM_Dataset, a corpus of 100 000 entries, by integrating data from ShenNong_TCM_Dataset and SymMap v2.0, and synthesizing additional samples via retrieval-augmented generation (RAG) and persona-driven generation. The dataset comprehensively covers diagnostic inquiries, prescriptions, and herbal knowledge. Utilizing P-Tuning v2, we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM. A multi-dimensional evaluation framework, assessing accuracy, coverage, consistency, safety, professionalism, and fluency, was established using metrics such as bilingual evaluation understudy (BLEU), recall-oriented understudy for gisting evaluation (ROUGE), metric for evaluation of translation with explicit ordering (METEOR), and LLM-as-a-Judge with expert review. Qualitative analysis was conducted across four simulated clinical scenarios: symptom analysis, disease treatment, herb inquiry, and failure cases. Baseline models included GLM-4-9B-Chat, DeepSeek-V2, HuatuoGPT-II (7B), and GLM-4-9B-Chat (freeze-tuning). Results: QingNangTCM achieved the highest scores in BLEU-1/2/3/4 (0.425/0.298/0.137/0.064), ROUGE-1/2 (0.368/0.157), and METEOR (0.218), demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy, coverage, and consistency. Although its ROUGE-L score (0.299) was lower than that of HuatuoGPT-II (7B) (0.351), it significantly outperformed domain-specific models in expert-validated win rates for professionalism (86%) and safety (73%). Qualitative analysis confirmed that the model strictly adheres to the “symptom-syndrome-pathogenesis-treatment” reasoning chain, though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes. Conclusion Combining domain-specific corpus construction with parameter-efficient prompt tuning enhances the reasoning behavior and domain adaptation of LLMs for TCM-related tasks. This work provides a technical framework for the digital organization and intelligent utilization of TCM knowledge, with potential value for supporting diagnostic reasoning and medical education.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

Objective To explore the diagnostic value of brain cord blood flow ultrasound combined with glucose metabolism indexes in the patients with preeclampsia(PE)complicated with fetal growth restriction(FGR).Methods This study was a prospective cohort case-control study.A total of 198 PE patients admitted to the hospital from January 2017 to January 2022 were collected and divided into group A(PE patients com-plicated with FGR,101 cases)and group B(PE patients without FGR,97 cases)according to whether they were complicated with FGR.45 pregnant women with healthy prenatal examination in the hospital were se-lected as group C,and the differences of brain cord blood flow ultrasound indexes and glucose metabolism inde-xes among the three groups and the efficiency for diagnosing PE complicated with FGR were analyzed.Results Fast-ing blood glucose and fasting insulin levels in group A,group B and group C were gradually decreased(P＜0.05).The peak systolic flow velocity/peak diastolic flow velocity(S/D),resistance index(RI)and pulsatility index(PI)of middle cerebral artery(MCA)of fetus in group A,group B and group C increased gradually(P＜0.05).The levels of umbilical artery(UA)of fetus in group A,group B and group C decreased gradually(P＜0.05).The area under the curve of fasting insulin,fasting blood glucose,S/D,RI and PI of MCA,S/D,RI,PI of UA and the combined detection were 0.782,0.748,0.765,0.836,0.805,0.758,0.811,0.795 and 0.895,respectively.The diagnostic efficiency of combined detection was higher than that of single diagnosis(Z=4.327,4.862,4.551,3.400,3.946,4.679,3.742,4.102,P＜0.05).Conclusion The combined detection of glucose metabolism indexes and brain cord blood flow ultrasound indexes is of great value in the differential diagnosis of patients with PE complicated with FGR,and has good clinical application value.

Rheumatoid arthritis(RA)is a common autoimmune disease with synovitis as core pathological manifestation,with strong injury and high disability rate,which can not be cured completely at present.Recent studies have shown that tumor necro-sis factor receptor-related factor 6(TRAF6),as a ubiquitin ligase E3,plays a key role in autoimmune diseases and inflammatory diseases through a variety of pathways.This article reviews structure,function,ubiquitin regulation of TRAF6 and research progress of pathogenesis of RA.

Rheumatoid arthritis(RA)is a common autoimmune disease with synovitis as core pathological manifestation,with strong injury and high disability rate,which can not be cured completely at present.Recent studies have shown that tumor necro-sis factor receptor-related factor 6(TRAF6),as a ubiquitin ligase E3,plays a key role in autoimmune diseases and inflammatory diseases through a variety of pathways.This article reviews structure,function,ubiquitin regulation of TRAF6 and research progress of pathogenesis of RA.

Objective:To analyze the epidemiology, and infant outcomes of congenital diaphragmatic hernia (CDH) in Beijing.Methods:This retrospective study involved cases diagnosed with CDH among 877 230 fetuses/infants monitored by the Beijing Birth Defects Monitoring System from January 2018 to December 2022. Data on the occurrence of CDH, prenatal diagnosis, and infant mortality were analyzed. The statistical method was the Chi-square test (or Fisher's exact test). Results:(1) A total of 254 CDH cases were included in this study. During the study period, the incidence of CDH throughout the pregnancy and the perinatal period was 0.29 per thousand (254/877 230) and 0.17 per thousand (153/877 230), respectively. (2) Among the 254 cases, 79 (31.1%) underwent prenatal genetic diagnosis, 6.3%(5/79) copy number varations were detected, including one case of like pathogenic and four cases with types of variation unreported. The proportions of prenatal genetic diagnosis from 2018 to 2022 showed no statistically significant difference ( χ2trend=2.86, P=0.091). The gestational age at prenatal diagnosis for 241 cases was (23.0±6.4) weeks, ranging from 13 to 38 weeks; 130 cases (53.9%) were diagnosed before 25 weeks of gestation. The proportion of genetic diagnosis was higher in the group diagnosed by ultrasound before 25 weeks (43.1%, 56/130) compared to the group diagnosed at or after 25 weeks (20.7%, 23/111) ( χ2=12.59, P<0.001). (3) A total of 146 live births were recorded, with the proportion of continuing pregnancy to live birth after prenatal diagnosis being 55.2% (133/241), with no significant difference across the years. The proportion of continuing pregnancy to live birth after prenatal diagnosis in the isolated CDH group was 64.5% (100/155), higher than the 38.3% (33/86) in the non-isolated group ( χ2=15.57, P<0.001). The live birth rate for those diagnosed prenatally at<25 weeks of gestation (26.2%, 34/130) was lower than for those diagnosed at≥25 weeks of gestation (89.2%, 99/111) ( χ2=93.67, P<0.001). (4) Among the 146 live-born infants, 28 (19.2%) died during infancy. All 28 cases were prenatally diagnosed with CDH. The mortality rate of CDH infants born in tertiary obstetric institutions (17.9%, 24/134) showed a trend towards being lower than that in secondary institutions (4/12), but the difference was not statistically significant (Fisher's exact test, P=0.245). Among the 118 surviving infants, seven were abandoned from treatment, and of the remaining 111, 104 (93.7%) were treated at the Children's Hospital, Capital Institute of Pediatrics. The infant mortality rate at this institution (15.4%, 16/104) showed a trend towards being lower than that at other institutions (3/7), but the difference was not statistically significant (Fisher's exact test, P=0.096). The infant mortality rate for those diagnosed prenatally at<25 weeks of gestation (38.2%, 13/34) was higher than for those diagnosed at≥25 weeks of gestation (15.2%, 15/99) ( χ2=6.78, P=0.009). Conclusions:Beijing achieved good secondary and tertiary prevention outcomes in prenatal diagnosis and reducing infant mortality. The concentration of neonatal surgical resources is beneficial for accumulating surgical experience and reducing infant mortality.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Hepatectomy is the most effective method for the treatment of liver cancer. Asso-ciating liver partition and portal vein ligation for staged hepatectomy (ALPPS) provides resectable opportunities for patients with unresectable or borderline resectable liver cancer. Traditional ALPPS procedures involve a short interval between two stages of the surgery, leading to a higher incidence of perioperative complications and mortality. The authors present a case of two-stage hepatectomy. Initially, laparoscopic ligation of the right hepatic artery and portal vein was performed. To prevent tumor progression after the first stage of surgery, combined immunotherapy and targeted therapy were administered. Three months later, a successful right hemihepatectomy was performed. Postoperative histopathological examination revealed hepatocellular carcinoma with extensive tumor necrosis. A 15-month follow-up showed no tumor recurrence. This indicated that two-stage hepatectomy including simultaneous ligation of the hepatic artery and portal vein, combined with two-stage hepatectomy plus immunotherapy and targeted therapy, showed considerable promise for borderline resectable liver cancer.

Objective:To evaluate an effective manner to replace the drainage tube due to drainage complications during the irrigation treatment of abdominal infection after pancreaticoduodenectomy (PD).Methods:Clinical data of 39 patients with abdominal infection after PD due to drainage complications who were successfully treated by replacement of the drainage tubes with continued flushing in the Department of Hepatobiliary Surgery, Yuncheng Central Hospital Affiliated to Shanxi Medical University from August 2020 to August 2023 were retrospectively analyzed, including 23 males and 16 females, aged (54.8±9.6) years. According to the fashion of tube replacement, patients were divided into the observation group ( n=21), in which a flushing tube was placed through the original abdominal drainage tube sinus tract combined with external negative pressure suction; and the control group ( n=18), in which two parallel drainage tubes were placed through the original abdominal drainage tube sinus tract for flushing and drainage. The two groups were compared in terms of indicators before tube replacement, including the primary tumor classification, incidence of pancreatic fistula and biliary fistula after PD, complications of abdominal drainage, time from the surgery to tube replacement; and indicators after tube replacement, including total hospital stay, hospitalization cost, continuous abdominal lavage time, fever and elevated white blood cell count, number of dressing changes, etc. Results:There were no significant difference in the primary tumor classification, incidence of pancreatic fistula and biliary fistula after PD, complications of abdominal drainage, and time from PD to tube replacement between the two groups before tube replacement (all P>0.05). After tube replacement, the total hospitalization time(32.7±1.9 vs 44.7±14.5, d), hospitalization cost (67 604±16 052 vs 91 845±19 826, yuan), continuous abdominal lavage time [4.0 (3.0, 5.0) vs 9.0 (8.0, 10.8), d], fever [23.8% (5/21) vs 55.6% (10/18)] and leukocytosis rate [28.6% (6/21) vs 66.7% (12/18)], and times of dressing change times [10.0 (7.0, 13.0) vs 22.0 (18.2, 27.0)] of the observation group were lower than those of the control group (all P<0.05). Conclusion:Inserting a flushing tube through the sinus tract of original abdominal drainage tube combined with external negative pressure drainage is an effective way to manage the abdominal infection after PD surgery due to drainage complications, featuring good irrigation and drainage, short irrigation time, and early control of the abdominal infection.