ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

Objective To evaluate the long-term survival of patients with T1a-bN0M0 non-small cell lung cancer (NSCLC) after sublobar resection. Methods Patients with T1a-bN0M0 NSCLC who underwent sublobar resection from 2004 to 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database, and divided into a segmentectomy group and a wedge resection group according to the resection method. After propensity-score matching at a ratio of 1:1, the overall survival (OS) and disease-specific survival (DSS) of patients were analyzed using Cox regression model, log-rank test, and restricted mean survival time (RMST). Results A total of 3262 patients were included in the study, including 1321 males and 1941 females, with a median age of 69.0 years. Among them, 2419 patients were in the wedge resection group and 843 patients were in the segmentectomy group. After matching, 843 pairs of patients were obtained. The results showed that the 10-year DSS rate (68.0% vs. 60.6%, P=0.011) and 10-year OS rate (40.8% vs. 37.0%, P=0.049) of the segmentectomy group were better than those of the wedge resection group, while there was no statistical difference in the 5-year DSS rate (82.9% vs. 79.5%, P=0.112) or 5-year OS rate (68.9% vs. 64.9%, P=0.096). Multivariate Cox regression analysis revealed that male gender [HR=1.54, 95%CI (1.28-1.86), P<0.001] and age [HR=1.02, 95%CI (1.01-1.03), P<0.001] were independent risk factors for DSS, while increased number of regional nodes dissected (RND) [HR=0.98, 95%CI (0.96-1.00), P=0.018] and segmentectomy [HR=0.82, 95%CI (0.68-0.98), P=0.030] served as protective factors. For OS, male gender [HR=1.54, 95%CI (1.35-1.75), P<0.001], age [HR=1.04, 95%CI (1.03-1.04), P<0.001], and histological subtypes of squamous cell carcinoma [HR=1.62, 95%CI (1.41-1.86), P<0.001] or large cell carcinoma [HR=1.64, 95%CI (1.07-2.52), P=0.023] were identified as independent risk factors, whereas increased RND was a protective factor [HR=0.98, 95%CI (0.97-0.99), P=0.002]. Surgical approach was not an independent prognostic factor for OS. Subgroup analysis showed that segmentectomy had a better 10-year OS-RMST in patients with adenocarcinoma (P=0.045), right lower lobe tumor (P=0.014), and tumor diameter ≤1.6 cm (P=0.006). Conclusion Increasing lymph node dissection during sublobar resection may improve prognosis. Compared with wedge resection, segmentectomy may improve the long-term DSS rate of patients with T1a-bN0M0 NSCLC.

ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article， based on the formulation compatibility analysis technology of "Tangye Jingfa Tu"， clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases， providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines， covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance， Work Injury Insurance， and Maternity Insurance Drug Catalogue （2023） （more than 50% of the total）， were selected for the study. Within the knowledge system of "Tangye Jingfa Tu"， the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally， the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills， Danshen tablets， Qili Qiangxin capsules， Breviscapine tablets， etc.， covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines， salty flavor was the most common （48）， followed by pungent （33）， and sweet （26）. According to the dominant herbal flavor， salty flavor was the most common （37）， followed by pungent （9）， and sour （5）. According to the dominant herbal quantity， salty flavor was the most common （27）， followed by sour （7）， and pungent （5）. Furthermore， Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example， most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen （9/10）， most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver （7/8）， and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys （6/6）. However， the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas， as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty， sour， and pungent flavors， which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart， heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.

OBJECTIVES: To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry. RESULTS: In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis. CONCLUSIONS DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Colitis, Ulcerative/metabolism* ; Dextran Sulfate/adverse effects* ; Male ; Inflammasomes/metabolism* ; Mice ; Benzoquinones/therapeutic use* ; Th17 Cells ; Caspase 1/metabolism*

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

OBJECTIVE: To investigate the effectiveness of basal osteotomy of the first metatarsal combined with first metatarsophalangeal joint replacement for the treatment of hallux valgus combined with hallux rigidus. METHODS: A retrospective analysis was conducted on the medical records of 15 patients (16 feet) with hallux valgus combined with hallux rigidus who underwent first metatarsal basal osteotomy combined with first metatarsophalangeal joint replacement between May 2019 and December 2024. The patients included 1 male and 14 females, aged 60-80 years, with an average age of 68.5 years. According to the Mann classification of hallux valgus, 2 feet were moderate and 14 feet were severe. According to the Hallux Rigidus Coughlin grading, 12 feet were grade 3 and 4 feet were grade 4. The evaluation indicators included hallux valgus angle (HVA) and intermetatarsal angle (IMA) measured on weight-bearing X-ray film at preoperation and last follow-up; the American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analogue scale (VAS) score were used to evaluate the improvement of walking function, metatarsophalangeal joint function, and pain relief in patients. RESULTS: All patients underwent surgery successfully without complications such as vascular or nerve injury during operation. One foot developed a superficial incisional infection postoperatively, which healed after dressing changes; the remaining 15 feet had primary incision healing. All patients were followed up 5-55 months, with an average of 17.5 months. All osteotomies achieved bony union, with a union time ranging from 8 to 13 weeks, averaging 11.8 weeks; no elevation of the first metatarsal was observed. At last follow-up, no complications such as prosthesis loosening, dislocation, fracture, toe shortening, bone dissolution, synovial reaction, or metatarsalgia was found. The appearance and function of the affected feet significantly improved, and the pain significantly relieved. At last follow-up, the HVA, IMA, AOFAS score, and VAS score showed significant differences when compared with preoperative values ( P<0.05). CONCLUSION Basal osteotomy of the first metatarsal combined with first metatarsophalangeal joint replacement for the treatment of hallux valgus with hallux rigidus can correct deformities through osteotomy, restore the normal flexion-extension axis of the metatarsophalangeal joint, relieve pain, and preserve a certain degree of mobility, achieving good short- and mid-term effectiveness.
Humans ; Male ; Female ; Hallux Valgus/diagnostic imaging* ; Osteotomy/methods* ; Aged ; Middle Aged ; Metatarsophalangeal Joint/surgery* ; Retrospective Studies ; Hallux Rigidus/diagnostic imaging* ; Aged, 80 and over ; Metatarsal Bones/surgery* ; Treatment Outcome ; Arthroplasty, Replacement/methods*

OBJECTIVE: To investigate the effectiveness of endoscopic-assisted median nerve decompression with one-stage extensor indicis proprius (EIP) tendon transfer for reconstruction of thumb abduction in patients with severe carpal tunnel syndrome (CTS). METHODS: The clinical data of 12 patients with severe CTS who met the selection criteria between December 2019 and December 2024 were retrospectively analyzed. There were 2 males and 10 females with an average age of 55.4 years ranging from 35 to 67 years. The symptom duration of CTS was 12-120 months (mean, 48.7 months) and the thenar muscle atrophy duration was 6-48 months (mean, 13.4 months). The median nerve was released with the help of endoscope, and the EIP tendon was transferred to reconstruct the abduction function of the thumb. The operation time and complications were recorded. Two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, and pinch force of the thumb were measured and compared before operation and at last follow-up, and the effectiveness was evaluated by Kapandji score and Disabilities of the Arm, Shoulder and Hand (DASH) score. The satisfaction of the operation was evaluated at last follow-up. RESULTS: All surgeries were successfully completed with a mean operation time of 54 minutes (range, 45-68 minutes). All patients were followed up 6-50 months, with an average of 15.3 months. There was no complications such as wound infection, scar pain of wrist, or tendon rupture of transposition, and there were 3 cases of mild limitation of finger extension in the donor site of index finger. At last follow-up, two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, Kapandji score, and DASH score were significantly better than those before operation ( P<0.05), but there was no significant difference in thumb pinch force between pre- and post-operation ( P>0.05). The evaluation of surgical satisfaction showed that 7 cases were very satisfied and 5 cases were satisfied. CONCLUSION The combination of endoscopic-assisted median nerve decompression and one-stage EIP tendon transfer effectively improves hand function and quality of life in patients with severe CTS by restoring thumb abduction and alleviating neurological symptoms.
Humans ; Tendon Transfer/methods* ; Male ; Middle Aged ; Carpal Tunnel Syndrome/physiopathology* ; Female ; Decompression, Surgical/methods* ; Aged ; Adult ; Thumb/physiopathology* ; Endoscopy/methods* ; Retrospective Studies ; Median Nerve/surgery* ; Treatment Outcome ; Plastic Surgery Procedures/methods*

Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear. Experimental animal models are valuable tools for exploring the etiology, pathogenesis, and potential interventions for CA and PCAS. Current CA animal models include electrical induction of ventricular fibrillation (VF), myocardial infarction, high potassium, asphyxia, and hemorrhagic shock. Although these models do not fully replicate the complexity of clinical CA, the mechanistic insights they provide remain highly relevant, including post-CA brain injury (PCABI), post-CA myocardial dysfunction (PAMD), systemic ischaemia/reperfusion injury (IRI), and the persistent precipitating pathology. Summarizing the methods of establishing CA models, the challenges encountered in the modeling process, and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
Animals ; Disease Models, Animal ; Post-Cardiac Arrest Syndrome/physiopathology* ; Heart Arrest/physiopathology* ; Humans ; Ventricular Fibrillation/complications*

Objective:To observe the clinical efficacy of traditional Chinese medicine(TCM)essential oil Tuina(Chinese therapeutic massage)combined with conventional Western medication in treating hypertension and its influence on TCM symptoms and anxiety.Methods:Eighty patients with hypertension were included and divided into an observation group and a control group using the random number table method,with 40 cases in each group.The control group was treated with conventional oral Western medication once a day.The observation group was treated with additional TCM essential oil Tuina once every other day.The two groups were treated for 4 weeks.The changes in blood pressure,TCM symptom score,and anxiety,as well as safety,were observed after treatment.Results:After treatment,the systolic blood pressure,diastolic blood pressure,TCM symptom score,and Hamilton anxiety scale score in the two groups were lower than those before treatment(P<0.05),and those of the observation group were lower compared to the control group with statistically significant differences(P<0.05).There were no adverse reactions,such as allergy and dry cough,in the two groups.Conclusion:Based on conventional Western medication,TCM essential oil Tuina was safe and effective in the treatment of hypertension,which both reduced blood pressure and improved clinical symptoms and anxiety.