This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

OBJECTIVE: To explore the effectiveness of the flexor digitorum longus (FDL) transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy in the treatment of stage ⅠAB progressive collapsing foot deformity (PCFD). METHODS: Between January 2019 and September 2023, 19 patients (19 feet) with stage ⅠAB PCFD were treated with FDL transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy. There were 11 males and 8 females, aged 18 to 60 years, with an average age of 45.5 years. Nine cases were on the left foot and 10 cases on the right foot. The disease duration was 9-21 months, with an average of 12.3 months. Postoperatively, the effectiveness was evaluated by visual analogue scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, and Tegner score. Based on X-ray films, the talonavicular coverage angle (TNCA), talus-first metatarsal angle (T1MT), Meary angle, and pitch angle were measured. The plantar pressure parameters of the foot were measured by the Footscan plantar pressure measurement system, including peak pressure and load of the forefoot, midfoot, and hind foot. The patients' satisfaction with the surgical outcome was evaluated. RESULTS: All 19 surgeries were successfully completed. One patient had poor incision healing after operation, while the incisions of the remaining patients healed by first intention. All patients were followed up 12-28 months (mean, 16.8 months). At last follow-up, the VAS score significantly decreased compared with that before operation, and the AOFAS score and Tegner score significantly increased ( P<0.05). Radiological measurements showed that the TNCA, T1MT, Meary angle, and Pitch angle all significantly improved compared with those before operation ( P<0.05). Plantar pressure tests indicated that the peak pressures of the forefoot and midfoot significantly reduced compared with those before operation ( P<0.05), while the peak pressure of the hind foot showed no significant change ( P>0.05). The forefoot load significantly increased and the midfoot load decreased compared with those before operation ( P<0.05), while the hind foot load showed no significant change ( P>0.05). The total satisfaction rate of patients with the surgical outcome (very satisfied+satisfied) reached 84.2% (16/19). CONCLUSION The FDL transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy can effectively correct the stage ⅠAB PCFD, improve the abnormal distribution of plantar pressure and load, alleviate foot pain symptoms, and improve foot movement function. The patient's satisfaction is high. However, the long-term effectiveness still needs to be further observed and clarified.
Humans ; Female ; Male ; Osteotomy/methods* ; Adult ; Middle Aged ; Calcaneus/surgery* ; Young Adult ; Adolescent ; Tendon Transfer/methods* ; Treatment Outcome ; Plastic Surgery Procedures/methods* ; Foot Deformities/surgery* ; Ligaments, Articular/surgery*

OBJECTIVE: Objective To investigate the relationship between cervical disc herniation and C₀-C₂ Cobb angle. METHODS: The clinical data of 301 patients with cervical disc herniation from 2020 to 2024 were retrospectively analyzed. The median value of C₀-C₂ Cobb angle measurements from 301 patients was used as the boundary, cervical disc herniation patients were divided into two groups, C₀-C₂ Cobb angle <28.50 group and 151 patients with C₀-C₂ Cobb angle≥28.50 group. Among them, 150 patients in C₀-C₂ Cobb angle <28.50 group included 53 males and 97 females, aged 23 to 76 (57.32±12.55) years, with a disease duration of 7 to 19 (13.81±5.32) months;the othor 151 patients with C₀-C₂ Cobb angle≥28.50 group including 61 males and 90 females, aged 25 to 74 (56.86±12.51) years, with a disease duration of 8 to 18 (14.13±5.56) months. The cervical lordosis angle (C₀-C₂ Cobb angle and C₂-C₇ Cobb angle), T₁ inclination slope (T₁S) and cervical sagittal axial distance (C₂-C₇ SVA) were measured on the lateral cervical radiographs. The correlation between C₀-C₂ Cobb angle and cervical disc herniation range, protrusion position, average protrusion size and other parameters was analyzed. RESULTS: When the C₀-C₂ Cobb angle<28.50°, the average protrusion size was (2.21±0.56) mm, the C₂-C₇ Cobb angle was (19.92±12.06)° and the C₂-C₇ SVA was (1.10±1.20) mm. When the C₀-C₂ Cobb angle≥28.50°, the average protrusion size was (2.38±0.60) mm, the C₂-C₇ Cobb angle was (12.01±13.09 )°, the C₂-C₇ SVA was (1.53±1.36) mm, and the difference was statistically significant (P<0.05). Between the two groups of patients with C₀-C₂ Cobb angle < 28.50° and C₀-C₂ Cobb angle≥28.50°, there were significant differences in the size of C_3,4, C_4,5, C_5,6, C_6,7, C₇, T₁ disc herniation in single segment (P<0.05 ). C₀-C₂ Cobb angle was correlated with age(r=-0.135, P<0.05 ), C₂-C₇ Cobb angle (r=-0.382, P<0.01 ), C₂-C₇ SVA (r=0.293, P<0.01), average protrusion size (r=0.139, P<0.05), and the size of C_3,4 (r=0.215, P<0.01 ), C_4,5 (r=0.176, P<0.01 ), C_5,6 (r=0.144, P<0.05 ), C_6,7 (r=0.158, P<0.05 ), C₇T₁ (r=0.535, P<0.05) disc herniation. CONCLUSION There is a positive correlation between C₀-C₂ Cobb angle and the size of cervical disc herniation. C₀-C₂ Cobb angle can reflect the degree of cervical disc herniation. Previous studies have shown that the biomechanical changes between C₀-C₂ Cobb angle, C₂-C₇ Cobb angle, C₂-C₇ SVA and cervical extensor muscle group may be risk factors for accelerating cervical disc herniation and this may be one of the mechanisms that C₀-C₂ Cobb angle is positively correlated with the size of cervical disc herniation.
Humans ; Male ; Female ; Middle Aged ; Intervertebral Disc Displacement/physiopathology* ; Adult ; Cervical Vertebrae/diagnostic imaging* ; Aged ; Retrospective Studies ; Young Adult

Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

OBJECTIVES: To assess the therapeutic effect of aucubin in mice with knee osteoarthritis (KOA) and investigate the underlying mechanism. METHODS: Sixty C57BL/6J mice were randomized equally into sham operation group, KOA model group, glucosamine (positive control) treatment group, and low-, medium-, and high-dose aucubin treatment groups (2, 4, and 8 mg/kg, respectively). KOA mouse models were established by transection of the anterior cruciate ligament (ACL), and the treatment was initiated on day 1 postoperatively and administered weekly for 8 weeks. Safranin O-fast green staining, immunohistochemistry, and microCT were used to evaluate the changes in cartilage pathology, inflammatory protein expression, and subchondral bone volume fraction (BV/TV). The expression levesl of COL2, SOX9, p-P65, IL-1β and MMP13 proteins in the cartilage tissues were detected using Western blotting. In a chondrocyte model with IL-1β treatment for mimicking KOA, the effect of aucubin on chondrogenic differentiation was observed with Alcian blue and Safranin O staining, and cellular COL2, SOX9 and TNF‑α mRNA expressions were detected with RT-qPCR. RESULTS: Compared with those in the model group, the mouse models receiving aucubin treatment showed significantly upregulated COL2 and SOX9 protein levels and downregulated p-P65, IL-1β and MMP13 expressions in the cartilage tissues. In the IL-1β-induced chondrocyte model, aucubin treatment significantly upregulated the mRNA expressions of SOX9 and COL2 but lowered the mRNA expression of TNF-α. Alcian blue and Safranin O staining confirmed that aucubin promoted the synthesis of cartilage extracellular matrix and enhanced chondrogenic differentiation of the cells. CONCLUSIONS Aucubin can effectively alleviate KOA in mice by inhibiting NF‑κB-mediated cartilage inflammation, promoting cartilage matrix synthesis, and improving subchondral bone microstructure.
Animals ; Mice, Inbred C57BL ; Mice ; Osteoarthritis, Knee/drug therapy* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Iridoid Glucosides/therapeutic use* ; SOX9 Transcription Factor/metabolism* ; Chondrocytes/drug effects* ; Male ; Interleukin-1beta/metabolism* ; Matrix Metalloproteinase 13/metabolism* ; Collagen Type II/metabolism* ; Disease Models, Animal

Objective To analyze the epidemiological distribution characteristics and influencing factors of treat-ment outcome of pulmonary tuberculosis(PTB)patients complicated with diabetes mellitus(DM)in Bijie City from 2017 to 2022,and provide reference for formulating prevention and control measures of PTB-DM.Methods The registered management cases of PTB patients combined with DM from the tuberculosis surveillance report informa-tion management system in Bijie City in 2017-2022 were collected.Changing trends in annual registration rates and successful treatment rates were analyzed with Joint-point regression models.Different characteristics between pa-tients with PTB-DM and PTB alone were conducted comparative analysis;the influencing factors of treatment out-come were analyzed by x2 test and binary logistic regression analysis.Results A total of 679 PTB-DM patients were registered in Bijie City from 2017 to 2022,accounting for 1.53％of total PTB patients,the annual registration rate increased from 1.11/100 000 in 2017 to 3.08/100 000 in 2022,with an increasing trend in the annual percentage change(APC=26.67％,95％CI:5.36％-52.29％,t=3.564,P=0.024).In the analysis on characteristics,the proportion of PTB-DM male patients,age ≥45 years and farmers,the ratio of direct consultation to transfer treat-ment,the pathogenicity positive rate,the proportion re-treatment,and rate of delay in consultation were all higher than those of PTB alone;successful treatment rate and proportion of floating population were all lower than PTB alone,difference were all statistically significant(all P＜0.05).The successful treatment rate of PTB-DM patients in Bijie City from 2017 to 2022 was 87.80％.Age,occupation,pathogenicity diagnosis results were influencing fac-tors for treatment outcome in patients with PTB-DM,with farmers(OR=3.68,95％CI:1.22-11.09),with pathogenicity positivity(OR=2.84,95％CI:1.24-6.50),and without pathogenic detection result+tuberculous pleurisy(OR=11.35,95％CI:2.16-59.74)being risk factors for successful treatment.Conclusion Although the proportion of PTB-DM in the total PTB patients in Bijie City from 2017 to 2022 was not high,it showed an up-ward trend;it is necessary to attach great importance to male,re-treated,farmer,and pathogenicity positivity co-morbid patients in Bijie City,and strengthen the two-way screening of PTB-DM in high-risk populations.

The concept of amplification feedback pathways represents an intersection between electronics and control theory,involving both amplification and feedback processes.It reveals the dynamic evolution mechanisms of systems under the combined influence of these two processes.In Traditional Chinese Medicine(TCM),Chest Bi syndrome is considered a"ben xu biao shi"condition,with its primary pathology located in the heart and closely related to other organs such as the liver,spleen and kidneys.This article focuses on the interrelationship between organ dysfunction and the imbalance of the Five Elements Theory.By applying amplification feedback theory and models,the study constructs and analyzes single-stage amplification feedback pathways involving the heart,liver and kidneys,as well as double-stage amplification feedback pathways involving the heart,liver,kidneys and spleen,in the context of multifactorial interactions such as heart and kidney Yang deficiency,Qi stagnation in the heart and chest,and spleen-stomach dysfunction.Particular emphasis is placed on analyzing the phenomena of deep feedback and self-excited oscillation,and specific formulas and clinical evidence are used to validate the analysis results,clarifying the role of relevant organ function changes in the pathogenesis of Chest Bi syndrome.The article aims to provide new insights into the complex pathogenesis of refractory diseases from a control theory perspective,offering new directions for modernizing TCM research with digital technology and theoretical support for future simulation-based digital systems guided by TCM theory.

Objective:To retrieve, evaluate, and summarize the evidence on prevention and management of chronic venous disease of the lower extremities, so as to provide reference for clinical practice.Methods:Clinical decisions, guidelines, evidence summaries, and expert consensus on chronic venous diseases of the lower extremities were systematically retrieved from UpToDate, Joanna Briggs Institute Evidence-Based Health Care Center Database, National Institute for Health and Clinical Excellence, Registered Nurses' Association of Ontario, New Zealand Guidelines Group, National Health and Medical Research Council, Guidelines International Network, Medlive, PubMed, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Data, and specialized collaborative websites including the Society for Vascular Surgery, American Vein and Lymphatic Society, American Venous Forum, and European Society for Vascular Surgery. The search period was from the establishment of the database to March 31, 2025.Results:A total of 18 articles were included, including three guidelines, five clinical decisions, four evidence summaries, and six expert consensus. Ultimately, 19 pieces of evidence were integrated from six aspects of diagnosis, clinical-etiology-anatomy-pathophysiology (CEAP) classification and severity assessment, risk factor assessment, prevention, lifestyle modification, stress management, and patient education and follow-up.Conclusions:Evidence included in this study indicates that the diagnosis of chronic venous disease of the lower extremities, along with CEAP classification and severity assessment, has been widely adopted. In clinical practice, emphasis should be placed on assessing risk factors, implementing preventive management and health education for high-risk patients, and conducting long-term follow-up to alleviate symptoms and thereby improve quality of life. It is recommended that clinical nursing staff conduct targeted evidence transformation based on specific clinical contexts to enhance the quality of clinical nursing.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To explore the CT manifestation characteristics of peripancreatic aneurysms related to pancreatitis (PRPA).Methods:A retrospective analysis was conducted on the clinical data of 15 patients with pancreatitis-related aneurysms collected in Deyang People's Hospital from June 2017 to February 2025. Among them, there were 11 males and 4 females, with an age of (56.5±16.9) years. Record the CT manifestations of the patients, and observe the PRPA tumor-carrying arteries, morphology, quantity, bleeding, calcification, dynamic changes, etc.Results:The CT results showed that there were a total of 26 PRPAs in 15 patients. The aneurysm walls of the PRPAs had no calcification, among which 12 cases were single and 1 case was double. Two cases were multiple. The patients were pancreatitis complicated with muscle fiber dysplasia. Among them, one case had 5 PRPAs and the other had 7 PRPAs. Of the 26 PRPAs, 12 were sac-like, 8 were beaded, 4 were fusiform, and 2 were columnar in shape. The numbers of aneurysm-carrying arteries and PRPA were as follows: 8 in the pancreaticoduodenal artery, 7 in the hepatic artery and its branches, 6 in the splenic artery and its branches, 2 in the left gastric artery, 1 in the gastroduodenal artery, 1 in the middle colonic artery, and 1 in the ileocolonic artery. The CT diagnosis report missed 16 PRPAs, with a missed diagnosis rate of 61.5% (16/26). Among the 11 ruptured PRPAs, 4 were missed, with a missed diagnosis rate of 36.4%. Three missed aneurysms were diagnosed by digital subtraction angiography, and one was retrospectively analyzed by CT. Among the 15 unruptured PRPAs, 12 were missed, with a missed diagnosis rate of 80.0%. All the missed aneurysms were detected by retrospective CT analysis. There were 2 images without re-examination and 24 images with re-examination. Among the PRPAs with re-examination images, 4 disappeared after interventional embolization on the same day, 1 relapsed after interventional embolization on the same day, with a reduction in volume and disappeared after 3 days. Three cases underwent elective interventional embolization, among which two shranked and one enlarged before interventional embolization. Among the 16 cases that did not receive interventional treatment, 7 disappeared on their own, 1 was completely liquefied, 5 shrank but did not disappear, 2 remained stable in size without any change, and 1 increased. Among the re-examined PRPA images, 7 showed signs of enlargement.Conclusion:The main characteristics of PRPA are high rupture rate, prone to missed diagnosis and dynamic changes in size.