The Dunhuang manuscript Fuxing Jue takes the "Tangye Jingfa Tu" as the core of its theory on prescription and compatibility. Its medication principles mainly include the "five elements principle of tonifying and purging" and the "five elements principle of elimination and transformation". Based on the differentiation of deficiency and excess in the five Zang organs， it flexibly applies medicinal properties， usage， and flavor transformation for tonifying and purging， forming its unique method of medication and compatibility. In Taiyin disease， "fullness syndrome" often occurs together with "diarrhea"， and these two conditions also serve as the primary indications for the middle-regulating formulas. Among them， Lizhong Wan （Tang） mainly address Taiyin deficiency. The three Xiexin Tang （Banxia Xiexin Tang， Gancao Xiexin Tang， Shengjiang Xiexin Tang） address Taiyin deficiency accompanied by pathogenic excess. The Sini Tangand Tongmai Sini Tang primarily treat dysfunction of the liver， spleen， and kidney with impaired opening and closing of Taiyin， manifesting as diarrhea. The medicinal flavors of middle-regulating formulas are pungent， sweet， and bitter， acting directly on the spleen of Taiyin. The pungent flavor induces purging of the spleen， sweet flavor tonifies the spleen， and bitter flavor eliminates lumps. When the constituent medicinal units of middle-regulating formulas are unified， the ratio of pungent to sweet flavors reflects the tonic and purgative strength of the formula. In addition， the two decoction methods， "short-term decoction to extract Qi" and "long-term decoction to extract flavor"， also influence the formula's tonifying and purgative effects. Based on the composition of flavors and special decoction methods， this article discusses the differences in the use of middle-regulating formulas for treating "“fullness syndrome" versus "diarrhea". Dysfunction of the spleen can give rise to various diseases. Therefore， middle-regulating formulas are not limited to treating "deficiency， cold， and dampness" syndromes. Later generations of physicians further modified Lizhong Tang to treat "excess， heat， and dryness" syndromes， laying a solid foundation for more flexible and effective clinical application of middle-regulating formulas.

The Dunhuang manuscript Fuxing Jue takes the "Tangye Jingfa Tu" as the core of its theory on prescription and compatibility. Its medication principles mainly include the "five elements principle of tonifying and purging" and the "five elements principle of elimination and transformation". Based on the differentiation of deficiency and excess in the five Zang organs， it flexibly applies medicinal properties， usage， and flavor transformation for tonifying and purging， forming its unique method of medication and compatibility. In Taiyin disease， "fullness syndrome" often occurs together with "diarrhea"， and these two conditions also serve as the primary indications for the middle-regulating formulas. Among them， Lizhong Wan （Tang） mainly address Taiyin deficiency. The three Xiexin Tang （Banxia Xiexin Tang， Gancao Xiexin Tang， Shengjiang Xiexin Tang） address Taiyin deficiency accompanied by pathogenic excess. The Sini Tangand Tongmai Sini Tang primarily treat dysfunction of the liver， spleen， and kidney with impaired opening and closing of Taiyin， manifesting as diarrhea. The medicinal flavors of middle-regulating formulas are pungent， sweet， and bitter， acting directly on the spleen of Taiyin. The pungent flavor induces purging of the spleen， sweet flavor tonifies the spleen， and bitter flavor eliminates lumps. When the constituent medicinal units of middle-regulating formulas are unified， the ratio of pungent to sweet flavors reflects the tonic and purgative strength of the formula. In addition， the two decoction methods， "short-term decoction to extract Qi" and "long-term decoction to extract flavor"， also influence the formula's tonifying and purgative effects. Based on the composition of flavors and special decoction methods， this article discusses the differences in the use of middle-regulating formulas for treating "“fullness syndrome" versus "diarrhea". Dysfunction of the spleen can give rise to various diseases. Therefore， middle-regulating formulas are not limited to treating "deficiency， cold， and dampness" syndromes. Later generations of physicians further modified Lizhong Tang to treat "excess， heat， and dryness" syndromes， laying a solid foundation for more flexible and effective clinical application of middle-regulating formulas.

OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Identifying drug-drug interactions (DDIs) is essential to prevent adverse effects from polypharmacy. Although deep learning has advanced DDI identification, the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits. Here, we developed a Multi-Dimensional Feature Fusion model named MDFF, which integrates one-dimensional simplified molecular input line entry system sequence features, two-dimensional molecular graph features, and three-dimensional geometric features to enhance drug representations for predicting DDIs. MDFF was trained and validated on two DDI datasets, evaluated across three distinct scenarios, and compared with advanced DDI prediction models using accuracy, precision, recall, area under the curve, and F1 score metrics. MDFF achieved state-of-the-art performance across all metrics. Ablation experiments showed that integrating multi-dimensional drug features yielded the best results. More importantly, we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs. Among 12 real-world adverse drug reaction reports, the predictions of 9 reports were supported by relevant evidence. Additionally, MDFF demonstrated the ability to explain adverse DDI mechanisms, providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.

Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

Objective:To investigate the feasibility and effectiveness of three-dimensional visualization technology in the precise diagnosis and treatment of locally advanced differentiated thyroid cancer(DTC).Methods:A retrospective analysis was conducted on the clinical data of 196 patients with locally advanced DTC treated at the 960th Hospital of the PLA from December 2021 to August 2023. The cohort included 71 male and 125 female patients, with a mean age of 43.7 years (rangd from 18 to 77 years). All patients underwent neck-enhanced CT scans and were divided into two groups: the study group( n=102), which underwent preoperative three-dimensional visualization of CT data, and the control group( n=94), which did not. Baseline data for both groups were matched using SPSS27.0 with 1∶1 propensity score matching (PSM) and the caliper value was 0.02. A total of 49 patients were included in each group, including 35 first-time surgeries and 14 reoperation. Among the 70 first-time surgeries, 29 patients underwent robotic surgery and 41 underwent open surgery. Among the 28 reoperations, 4 underwent robotic surgery and 24 underwent open surgery. In the study group, three-dimensional visual models were used to comprehensively evaluate the tumor and metastatic lesion size, spatial location, and adjacent relationship with surrounding organs, surgical treatments were guided by these models, whereas the control group relied on two-dimensional imaging for guidance. The clinical data were statistically analyzed using SPSS27.0. Results:All operations were successfully completed. There were no statistical differences in baseline data between the two groups( P>0.05). Among first-time surgeries, the study group showed shorter operation times [175(145, 200) min vs 205(182, 249) min, P<0.001], a lower incidence of postoperative chyle leak (0 vs 8.57%, P=0.027), a higher rate of robotic surgery (48.57% vs 34.28%, P=0.225), a greater number of harvested lymph nodes [46(40, 62) vs 37(28, 56), P=0.032], a greater number of cervical lymph node metastasis[15(7, 22) vs 5(1, 14), P=0.004] and a larger diameter of metastasis lymph nodes[12(10, 16) mm vs 4(1, 10) mm, P<0.001]. There were no significant differences in intraoperative blood loss, postoperative drainage days and incidence of hypoparathyroidism( P>0.05). During the reoperation, the study group had shorter operation times[103.5(95.0, 122.5) min vs 146.50(133.25, 172.25) min, P<0.001], less intraoperative blood loss[12.50(8.75, 22.50) mL vs 30.00(17.50, 35.00) mL, P=0.021], fewer postoperative drainage days[5.00(4.00, 6.00) d vs 6.00(5.00, 7.25) d, P=0.016] and a lower incidence of hypoparathyroidism(7.14% vs 42.86%, P=0.038).The robotic surgery rate was higher in the study group (21.42% vs 7.14%, P=0.596). There were no significant differences in lymph node dissection numbers, metastatic lymph node counts, or chyle leak incidences between the two groups ( P>0.05). No acute bleeding or incision infection occurred in any patient postoperatively. Conclusion:Three-dimensional visualization technology is an effective preoperative assessment method for evaluating the resectability of tumors and metastases lesions in locally advanced DTC. It enhances the accuracy and safety of surgery for locally advanced DTC.

Objective:To investigate the feasibility and safety of implementing a domestic vehicle-mounted remote mobile robotic surgical system in thyroid surgery applications, integrated with 5G communication technology.Methods:Using the main system located on the vehicle-mounted mobile robot operating platform of the 960th Hospital of PLA Joint Logistics Support Force and the slave system of Weifang Traditional Chinese Hospital, the remote radical thyroidectomy 5G communication technology, and analyze the clinical and information transmission data of two female patients who underwent remote mobile robot thyroid cancer surgery on October 21, 2024 at Weifang Traditional Chinese Medicine Hospital.Results:The remote radical thyroidectomy was conducted by the robosurgeons utilizing a vehicle-mounted mobile robotic surgical system, and the procedure was successfully completed without necessitating intermediate open surgery. The operation durations for patient 1 and patient 2 were 135 minutes and 108 minutes, respectively, with 7 and 13 lymph nodes dissected, respectively. The average delay in surgical data transmission was recorded at 61.9 milliseconds, with no instances of signal interruption or frame loss. The procedure proceeded smoothly, without any jamming, and the audio and video transmissions were consistently clear. Follow up for 21 days after surgery showed no complications such as hoarseness, skin damage, or lymphatic fistula.Conclusion:The implementation of a vehicle-mounted remote mobile robotic surgery system for thyroid surgery has demonstrated safety and feasibility. Furthermore, the utilization of the 5G network offers rapid data transmission and minimal latency, closely approximating the therapeutic efficacy of traditional robotic thyroidectomy.

Objective:To evaluate postoperative biochemical and clinical remission rates in patients with unilateral primary aldosteronism and analyze related influencing factors.Methods:A total of 406 patients of primary aldosteronism with confirmed subtyping, who underwent adrenalectomy and completed follow-up in the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to March 2022 were retrospectively enrolled. Clinical and biochemical data were recorded. Postoperative clinical and biochemical outcomes were assessed according to Primary Aldosteronism Surgery Outcome(PASO) consensus.Results:Complete biochemical success was achieved in 391(96.31%) of 406 primary aldosteronism patients, while partial and absent biochemical success in only 4(0.99%) and 11(2.71%) primary aldosteronism patients; Complete clinical success was seen in 217(53.45%) patients, and partial clinical success in 189(46.55%) patients. Compared to the partial clinical success group, the complete clinical success group was younger, had a greater proportion of women, a smaller body mass index, a shorter duration of hypertension, a smaller daily defined dose value for antihypertensive medication, a higher estimated glomerular filtration rate(eGFR), and a lower proportion of family history of hypertension and diabetes mellitus. Multifactorial logistic regression analysis further showed that gender( OR=2.49, 95% CI 1.42-4.35, P=0.001), body mass index( OR=1.16, 95% CI 1.05-1.28, P=0.003), antihypertensive drug daily defined dose( OR=1.83, 95% CI 1.37-2.44, P<0.001), family history of hypertension( OR=2.16, 95% CI 1.22-3.83, P=0.008), history of diabetes( OR=2.47, 95% CI 1.15-5.29, P=0.021), and eGFR( OR=0.98, 95% CI 0.97-0.99, P=0.001) were independent factors influencing clinical prognosis of primary aldosteronism. Conclusion:The postoperative complete biochemical success is higher in patients with unilateral primary aldosteronism, but only about half of all patients achieve complete clinical success.

Objective:To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS).Methods:In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value.Results:The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% ( n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% ( n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95% CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95% CI 78.88%-87.56%) and specificity was 60.50% (95% CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion:PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.