Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the regulatory effect of Wip1 phosphatase on hematopoietic function in the mouse spleen. METHODS: Wip1 knockout mice were bred, and the effect of Wip1 deletion on the proportion and number of hematopoietic stem/progenitor cells, as well as their mature subsets in mouse spleen was detected by flow cytometry. The Proteome Profiler^TM antibody array was used to analyze the role of Wip1 deletion on the expression of inflammatory cytokines in CD45^highCD11b⁺ myeloid cells sorted from mouse spleen. RESULTS: Wip1 deletion resulted in smaller size and significant reduction of cell number in the mouse spleen. The absolute numbers of hematopoietic stem/progenitor cells were decreased. Meanwhile, the absolute number of T and B lymphocytes also significantly declined. However, the proportion of erythroid progenitors and erythroid cells at various stage significantly increased, but the number of mature erythroid cells decreased. Furthermore, the myeloid cells and their subsets neutrophils, monocytes, CD45^highCD11b⁺ and CD45^lowCD11b⁺ were all reduced. CD45^highCD11b⁺ myeloid cells displayed proinflammatory phenotype in the spleen. CONCLUSION Wip1 gene deletion impairs normal hematopoietic function in the mouse spleen, leading to a significant reduction of mature hematopoietic cells of various lineages, and proinflammatory phenotype in CD45^highCD11b⁺ myeloid cells.
Animals ; Mice ; Spleen/cytology* ; Mice, Knockout ; Hematopoietic Stem Cells/cytology* ; Myeloid Cells/cytology* ; Protein Phosphatase 2C ; Hematopoiesis ; Flow Cytometry

Objective:To observe the effect of reconstruction of Achilles insertion with Suture bridge technology after extirpation of avulsed bones block in the treatment of Beavis type Ⅲ avulsion fracture of the calcaneal tuberosity.Methods:The retrospective analysis was used. From January 2013 to January 2023, 78 patients with Beavis type Ⅲ avulsion fracture of the calcaneal tuberosity, treated in the Department 1 of Foot and Ankle and Department 2 of Foot and Ankle of the second Hospital of Tangshan were selected as research objects. According to different operation performed, 41 patients with the reconstruction of Achilles insertion with Suture bridge technology after extirpation of avulsed bones block were divided into the observation group and 37 patients with the open reduction internal fixation (ORIF) were divided into the control group. The delayed wound healing rate and the Haglund malformation rate, Maryland foot score, the American Orthopedic Foot and ankle Society (AOFAS) ankle-hindfoot score, the pain Visual Analogue Scale/Score (VAS) score, the Victorian Institute of Sports Assessment-Achilles (VISA-A) score, Arner-Lindholm scale of One-year postoperative were compared between these two groups. The measurement data with normal or approximate normal distribution were analyzed using t test, count data using chi-square test for comparison of between groups.Results:One year after surgery, the incidence of Haglund malformation in the observation group was 4.88% (2/41), which was lower than the control group's 29.73% (11/37). The difference between the two groups was statistically significant ( χ2=8.65,P=0.003). The excellent and good rate of Maryland foot function assessment in the observation group was 85.37% (35/41) higher than that in the control group (56.76% (21/37), and the difference between the two groups was statistically significant ( χ2=7.86, P=0.005). The AOFAS ankle hind foot score of the observation group ((90.44±6.66) points) was higher than that of the control group ((82.84±7.43) points), and the difference between the two groups was statistically significant ( t=4.77, P<0.001). The pain score of the observation group ((1.51±1.05) points) was lower than that of the control group ((2.95±1.13) points), and the difference between the two groups was statistically significant ( t=-5.81, P<0.001). The Achilles tendon score of the observation group ((81.05±5.87) points) was higher than that of the control group ((71.62±8.60) points), and the difference between the two groups was statistically significant ( t=5.70, P<0.001). The excellent and good rate of Arner Lindholm treatment efficacy evaluation for Achilles tendon in the observation group was 87.80% (36/41), which was higher than that in the control group (67.57% (25/37)), and the difference between the groups was statistically significant. Conclusion:The treatment of Beavis Ⅲ type calcaneal nodule avulsion fracture by removing the bone fragment can simultaneously remove the hypertrophic osteophyte, hardened bone, and Haglund deformity of the calcaneus, and clean the degenerated Achilles tendon and inflammatory tissue around the insertion point; The use of suture bridge technology to reconstruct the Achilles tendon insertion point has the advantages of high fixed strength, allowing early functional exercise, avoiding secondary removal of internal fixation, and achieving satisfactory therapeutic effects, which is worthy of clinical promotion.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective: To investigate the correlation between the levels of calcitonin gene-related peptide α (CGRPα) and the poor responses to the treatment of phenylephrine in pregnant women with hypotension during caesarean section under intraspinal anesthesia. Methods : A total of 87 pregnant women who underwent intraspinal anesthesia cesarean section were recruited . They were grouped according to the presence or absence of hypotension after anesthesia and the response to ephedrine and Phe . As to Anesthesia-0 group , pregnant women had no hypo- tension , 35 cases (40. 2% ) ; Anesthesia-1 group , pregnant women had hypotension and good response to ephed- rine treatment , 12 cases (13 . 8% ) ; Anesthesia-2 group , pregnant women had hypotension and had poor response to ephedrine treatment , 6 cases (6. 9% ) ; Anesthesia-3 group , pregnant women had hypotension and good response to Phe treatment , 8 cases (9. 2% ) ; Anesthesia-4 group , pregnant women had hypotension and no response to Phe treatment , 26 cases (29. 9% ) . The levels of CGRPαin serum and placental tissues of pregnant women were deter- mined by ELISA . The rats pregnant normally. A hypotension rat model was established by intragastric administra- tion of risserpine . 50 rats were randomly divided into control group , model group , pregnancy group , model + preg- nancy group , model + pregnancy + phenylephrine group , with 10 rats in each group . Body weight of the rats was continuously monitored during the 2nd to 6th week of risserpine administration . Systolic blood pressure was meas- ured at the end of the 6th induction week . And the peripheral blood sample and placental tissues were collected and the levels of CGRPαwere determined . Results : The detection of CGRPαlevels in the pregnant women serum and placental tissues showed that compared with Anesthesia-0 group , CGRPαlevels in Anesthesia-1-4 groups serum were higher (P < 0. 05) . Compared with Anesthesia-3 group , serum CGRPαlevels in Anesthesia-4 group were higher (P < 0. 05) . Compared with Anesthesia-2 group , CGRPαlevels in Anesthesia-4 group serum were higher (P < 0. 05) . Compared with Anesthesia-0 group , tissues CGRPαlevels in Anesthesia-4 group were higher (P < 0. 05) . Compared with Anesthesia-3 group , CGRPαlevels in Anesthesia-4 group tissues were higher (P < 0. 05) . Compared with Anesthesia-2 group , CGRPαlevels in Anesthesia-4 group tissues were higher ( P < 0. 05) . From the 2nd to 6th week of hypotension modeling induction , compared with pregnancy group , body weight decreased in the model + pregnancy group and the model + pregnancy + phenylephrine group (P < 0. 05) . There was no signifi- cant difference in baseline systolic blood pressure among all groups (P > 0. 05) . At the end of the 6th week , com- pared with pregnancy group , systolic blood pressure decreased in model + pregnancy group and model + pregnancy + phenylephrine group(P < 0. 05) ; the levels of CGRPαin serum and placental tissues increased ( P < 0. 05) . Compared with model + pregnancy group , systolic blood pressure increased in model + pregnancy + phenylephrine group (P < 0. 05) . Conclusion The poor response of pregnant women with hypotension during caesarean section under intraspinal anesthesia to the treatment of phenylephrine may be related to the increased levels of CGRPαin placenta and peripheral blood .

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.