This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Objective:To compare the safety, number of lymph nodes removed, rate of lymph node metastasis, and prognosis between proximal gastrectomy (PG) and total gastrectomy (TG) in patients with Siewert types II and III adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, clinical data of patients diagnosed with adenocarcinoma of the esophagogastric junction at Changzhi People's Hospital, affiliated with Changzhi Medical College, between December 2019 and November 2022, were collected. Patients who had received neoadjuvant therapy, had multiple malignant lesions in the stomach, had concomitant malignancies in other organs, had incomplete clinical data, or had been lost to follow-up were excluded. The study cohort comprised 308 patients, 99 in the PG group and 209 in the TG group. To reduce confounding bias, propensity score matching was performed, matching patients for age, sex, body mass index, tumor diameter, and pathological stage in a 1:1 ratio, resulting in 73 patients in each group. The primary outcomes assessed were operative details, number of lymph nodes dissected, rate of lymph node metastasis, postoperative complications, duration of hospital stay, and follow-up and survival outcomes.Results:The PG group had a significantly shorter median operative time than did the TG group (250 vs. 280 minutes, Z = -4.970, P<0.001), with fewer cases of intraoperative blood loss >100 mL (30.1%[22/73] vs. 46.6%[34/73], χ2=4.171, P=0.041), and a smaller number of lymph nodes removed (median 33 vs. 46, Z =-4.774, P<0.001); all of these differences are statistically significant (all P<0.05). Differences between the two groups in postoperative hospital stay and postoperative complications were not statistically significant (both P>0.05). Furthermore, no statistically significant differences were found between the PG and TG groups in the number of lymph nodes dissected or the lymph node metastasis rates at stations No. 1, No. 2, No. 3, No. 4sa, No. 4sb, and No. 7 (all P> 0.05). Among the 209 patients in the TG group, analysis of risk factors for metastasis to distal perigastric lymph nodes (No.4d, No.5, and No.6) showed that patients with tumor diameters ≤4 cm and T1–T3 stage disease had significantly lower rates of metastasis to these lymph nodes than did patients with tumor diameters >4 cm and/or T4 stage disease (0/78 vs. 12/131 [9.2%]); these differences are statistically significant ( P=0.014). The median duration of follow-up for the entire cohort was 26 months. The 3-year overall survival rates for the PG and TG groups were 62.5% and 63.3%, respectively; this difference is not statistically significant (χ 2=0.330, P = 0.565). Multivariate analysis showed that older age ( P = 0.035) and advanced pathological stage ( P = 0.018) were significant independent risk factors that affected overall survival in patients with Siewert type II and III adenocarcinoma of the esophagogastric junction. Conclusions:PG is safe and feasible for patients with Siewert types II and III adenocarcinoma of the esophagogastric junction. The number of lymph nodes dissected and metastasis status were similar in the TG and PG groups.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

Objective:To compare the safety, number of lymph nodes removed, rate of lymph node metastasis, and prognosis between proximal gastrectomy (PG) and total gastrectomy (TG) in patients with Siewert types II and III adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, clinical data of patients diagnosed with adenocarcinoma of the esophagogastric junction at Changzhi People's Hospital, affiliated with Changzhi Medical College, between December 2019 and November 2022, were collected. Patients who had received neoadjuvant therapy, had multiple malignant lesions in the stomach, had concomitant malignancies in other organs, had incomplete clinical data, or had been lost to follow-up were excluded. The study cohort comprised 308 patients, 99 in the PG group and 209 in the TG group. To reduce confounding bias, propensity score matching was performed, matching patients for age, sex, body mass index, tumor diameter, and pathological stage in a 1:1 ratio, resulting in 73 patients in each group. The primary outcomes assessed were operative details, number of lymph nodes dissected, rate of lymph node metastasis, postoperative complications, duration of hospital stay, and follow-up and survival outcomes.Results:The PG group had a significantly shorter median operative time than did the TG group (250 vs. 280 minutes, Z = -4.970, P<0.001), with fewer cases of intraoperative blood loss >100 mL (30.1%[22/73] vs. 46.6%[34/73], χ2=4.171, P=0.041), and a smaller number of lymph nodes removed (median 33 vs. 46, Z =-4.774, P<0.001); all of these differences are statistically significant (all P<0.05). Differences between the two groups in postoperative hospital stay and postoperative complications were not statistically significant (both P>0.05). Furthermore, no statistically significant differences were found between the PG and TG groups in the number of lymph nodes dissected or the lymph node metastasis rates at stations No. 1, No. 2, No. 3, No. 4sa, No. 4sb, and No. 7 (all P> 0.05). Among the 209 patients in the TG group, analysis of risk factors for metastasis to distal perigastric lymph nodes (No.4d, No.5, and No.6) showed that patients with tumor diameters ≤4 cm and T1–T3 stage disease had significantly lower rates of metastasis to these lymph nodes than did patients with tumor diameters >4 cm and/or T4 stage disease (0/78 vs. 12/131 [9.2%]); these differences are statistically significant ( P=0.014). The median duration of follow-up for the entire cohort was 26 months. The 3-year overall survival rates for the PG and TG groups were 62.5% and 63.3%, respectively; this difference is not statistically significant (χ 2=0.330, P = 0.565). Multivariate analysis showed that older age ( P = 0.035) and advanced pathological stage ( P = 0.018) were significant independent risk factors that affected overall survival in patients with Siewert type II and III adenocarcinoma of the esophagogastric junction. Conclusions:PG is safe and feasible for patients with Siewert types II and III adenocarcinoma of the esophagogastric junction. The number of lymph nodes dissected and metastasis status were similar in the TG and PG groups.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

This article reported a case of pyruvate dehydrogenase E1-α deficiency suggested by abnormal brain development during prenatal ultrasound imaging. Prenatal ultrasound revealed a mild enlargement of bilateral cerebral ventricles and the possibility of intracranial hemorrhage in the fetus at 25 +1 weeks of gestation. MRI showed the fetus with absent corpus callosum, enlarged bilateral cerebral ventricles and paraventricular cysts. After genetic counseling and careful consideration, the couple opted for pregnancy termination. To clarify the cause of the disease, whole-exome sequencing was performed on the fetal skin to detect possible variants, and which revealed a frameshift mutation c.924_930dup(p.R311Gfs*5) in exon 10 of the PDHA1 gene. Sanger sequencing confirmed the mutation was a de novo pathogenic variant, indicating that the fetus was affected by pyruvate dehydrogenase E1-α deficiency.

Background: The widespread use of biological agents in recent years can improve the nutritional status of partial patients with Crohn's disease (CD) and change the course of the disease. Aims: To investigate the correlation between the nutritional risk and clinical and endoscopic features in CD patients treated with biological agents. Methods: Sixty⁃eight CD patients treated with biological agents from June 2021 to June 2022 at the First Affiliated Hospital of Anhui Medical University were enrolled. Nutritional risk screening was conducted by nutritional risk screening 2002 (NRS2002), and its correlation with clinical and endoscopic features was analyzed. Results: In 68 CD patients treated with biological agents, incidence of nutritional risk was 66.2%. There was statistically significant difference in incidence of nutritional risk in patients with different disease behaviors, SES⁃CD score and postoperative Rutgeerts score (all P<0.05). The incidence of nutritional risk was not correlated with age, lesion location, perianal lesion, CDAI score, and the interval between CD diagnosis and the use of biological agents (all P>0.05). Conclusions: The incidence of nutritional risk is high in CD patients treated with biological agents, and is correlated with CD disease behavior, SES ⁃ CD score, and postoperative Rutgeerts score.

With the widespread adoption of endoscopy and laparoscopy in the treatment of gastric cancer, the pivotal role of endoscopy in ensuring the quality of laparoscopic surgery has grown increasingly significant. Simultaneously, the complementary and collaborative role of laparoscopy in the endoscopic treatment of gastric cancer has garnered attention. The dual-endoscopic treatment model represents an inevitable trend in the evolution of precise and personalized healthcare. Currently, the fusion of endoscopy and laparoscopy manifests in diverse and multifaceted ways. The integration of dual-endoscopy necessitates transcending the boundaries between internal and surgical disciplines. The collaborative multidisciplinary platform-the Digestive Disease Center, centered on disease treatment, can streamline the diagnostic and treatment process, making it efficient, safe, and rational. This, in turn, allows dual-endoscopy to truly realize synergy and cooperation, leading to more precise, minimally invasive procedures, and maximal functional preservation in the treatment of gastric cancer. The authors elucidate the combined strategy of endoscopy and laparoscopy, aiming to establish a more rational dual-endoscopic diagnostic and treatment model for patients with gastric cancer.

OBJECTIVE: To observe the effect of Buyi Pishen acupuncture (acupuncture for invigorating spleen and kidney) on inflammatory factor and synovial cartilage matrix in adjuvant arthritis (AA) rats, and to explore the mechanism of acupuncture for rheumatoid arthritis (RA). METHODS: A total of 60 clean male Wistar rats were randomized into a normal group, a model group, a tripterygium wilfordii polyglycoside tablet (TWP) group and an acupuncture group, 15 rats in each group. Rats in the model group, the TWP group and the acupuncture group received intradermal injection of Freund's complete adjuvant (FCA) at right hind foot pad to induce the AA model. TWP suspension of 8 mg/kg was given by gavage in the TWP group. Acupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and right "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34) in the acupuncture group, 15 min a time, once a day. The intervention was given 15 days in both TWP group and acupuncture group. The foot-pad swelling degree before modeling, before and after intervention and the arthritis index (AI) score before and after intervention were calculated; the serum levels of interleukin (IL)-1β, IL-4, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA method; the ultrastructure and histomorphological changes of synovium issue were observed by transmission electron microscope and HE staining; the positive expression of matrix metalloproteinase (MMP)-3 and MMP-9 in synovium issue was detected by immunohistochemistry method. RESULTS: Before intervention, foot-pad swelling degree of the model group, the TWP group and the acupuncture group was increased compared with the normal group (P<0.01). After intervention, foot-pad swelling degree and AI score were increased compared with the normal group (P<0.01), foot-pad swelling degree and AI scores in the TWP group and the acupuncture group were lower than the model group (P<0.05), and those in the acupuncture group were decreased compared with the TWP group (P<0.05). The model group exhibited unclear nuclear membrane of synovial cells, chromatin pyknosis, massive inflammatory cell infiltration and hyperplasia in synovial tissue; the TWP group and the acupuncture group exhibited clear and smooth nuclear membrane of synovial cells, inapparent chromatin pyknosis, less inflammatory cell infiltration and hyperplasia in synovial tissue, the acupuncture group exhibited less matrix destruction as well. Compared with the normal group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were increased (P<0.01), while serum levels of IL-4 and IL-10 were decreased (P<0.01) in the model group. Compared with the model group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05, P<0.01), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the TWP group and the acupuncture group; compared with the TWP group, serum level of TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the acupuncture group. CONCLUSION Buyi Pishen acupuncture can effectively improve the injury of articular cartilage in AA rats, its mechanism maybe related to reducing the inflammatory reaction in synovium and inhibiting the degradation of articular cartilage matrix.
Acupuncture Therapy ; Animals ; Arthritis, Experimental/therapy* ; Cartilage, Articular ; Chromatin ; Hyperplasia ; Interleukin-10 ; Interleukin-4 ; Male ; Matrix Metalloproteinase 3 ; Matrix Metalloproteinase 9 ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha/genetics*