ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

ObjectiveTo observe the effect of serum containing Buyang Huanwutang on podocyte injury induced by high glucose in mice， and to explore its potential mechanism. MethodsMouse podocytes （MPC5） were cultured in vitro， and the optimal intervention concentration and time of serum containing Buyang Huanwutang were screened. Cells were divided into normal group （5.5 mmol·L^-1 glucose）， isotonic group （5.5 mmol·L^-1 glucose+24.5 mmol·L^-1 Mannitol）， high glucose group （30 mmol·L^-1 glucose）， blank serum group （30 mmol·L^-1 glucose+20% blank serum） and Buyang Huanwutang（30 mmol·L^-1 glucose+10% serum containing）. FerroOrange fluorescent probe was used to detect the level of iron （Fe²⁺） in cells. The level of reactive oxygen species （ROS） in cells was detected by Hoechst staining. The levels of glutathione （GSH） and malondialdehyde （MDA） in cells were detected by the kit. Enzyme-linked immunosorbent assay （ELISA） was used to determine the level of 4-hydroxynonenal （4-HNE）. Western blot was used to detect Desmin， podocyte hole membrane protein （Nephrin）， Podocalyxin， long-chain acyl-CoA synthetase 4（ACSL4）， member 11 of solute carrier family 7 （SLC7A11）， glutathione peroxidase 4（GPX4）， nuclear transcription factor E₂-related factor 2（Nrf2） and heme oxygenase -1（HO-1）. The mRNA expression levels of Desmin， Nephrin， Podocalyxin， ACSL4， SLC7A11， GPX4， Nrf2 and HO-1 were detected by real-time fluorescence quantitative polymerase chain reaction. ResultsCompared with the normal control group， the expressions of Desmin and ACSL4， the levels of Fe²⁺ and ROS， and the contents of MDA and 4-HNE in the high glucose group increased significantly， and the expressions of GSH， Nephrin， Podocalyxin， SLC7A11， GPX4， Nrf2 and HO-1 decreased（P<0.05， P<0.01）. There was no significant change in the above results in isotonic group. Compared with the high glucose group， the expressions of Desmin and ACSL4， the levels of Fe²⁺ and ROS， and the contents of MDA and 4-HNE in Buyang Huanwutang-containing serum group and Fer-1 group decreased significantly， and the expressions of GSH， Nephrin， Podocalyxin， SLC7A11， GPX4， Nrf2 and HO-1 increased（P<0.05， P<0.01）. There was no significant change in the above results in blank serum group. ConclusionBuyang Huanwutang medicated serum can alleviate podocyte injury induced by high glucose， and its mechanism is related to regulating Nrf2/HO-1 pathway and inhibiting ferroptosis.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVES: To investigate the therapeutic effect of the natural compound niranthin on Crohn's disease-like colitis in mice and explore the underlying molecular mechanisms. METHODS: In a mouse model of colitis induced by 2,4,6-trinitro-benzenesulfonic acid (TNBS), the therapeutic effect of niranthin was evaluated by observing the changes in body weight, disease activity index (DAI), and colon length of the mice. The levels of inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-17A and IL-10) in the intestinal mucosal tissue were detected using ELISA and quantitative real-time PCR (qRT-PCR). TUNEL staining and Western blotting were used to assess intestinal epithelial cell apoptosis and the expressions of Bcl-2 and Bax. The expression levels of tight junction proteins (ZO-1 and claudin-1) and the activation of the p38/JNK signaling pathway were investigated using Western blotting, and diprovocim intervention experiments were conducted to explore the molecular regulatory mechanism of niranthin. RESULTS: Niranthin treatment significantly increased body weight of TNBS-treated mice, lowered the DAI and histological inflammation scores, and increased colon length of the mice. The niranthin-treated mouse models showed obviously reduced protein and mRNA levels of IL-6, IL-1β, IL-17A, and TNF-α and upregulated expression of IL-10 in the colon tissue. TUNEL staining and Western blotting demonstrated that niranthin significantly inhibited intestinal epithelial cell apoptosis and activated the anti-apoptotic pathway in the mouse models. Niranthin treatment obviously upregulated the expression levels of ZO-1 and claudin-1 and downregulated the phosphorylation levels of p38 and JNK in the colon tissues of the mice. Diprovocim intervention obviously attenuated the inactivation of the p38/JNK signaling pathway induced by niranthin in the mouse models. CONCLUSIONS Niranthin ameliorates TNBS-induced Crohn's disease-like colitis in mice by inhibiting intestinal epithelial cell apoptosis and protecting the integrity of the intestinal barrier via regulating the activation of the p38/JNK signaling pathway.
Animals ; Apoptosis/drug effects* ; Mice ; Intestinal Mucosa/drug effects* ; Crohn Disease/drug therapy* ; MAP Kinase Signaling System/drug effects* ; Epithelial Cells/drug effects* ; Disease Models, Animal ; Signal Transduction/drug effects* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Male

Objective:The clinicopathological features of pulmonary epithelioid hemangioendothelioma (PEHE) were analyzed to provide guidance for clinical practice.Methods:The clinical manifestations, imaging examination, pathological morphology and molecular characteristics, treatment and prognosis of patients with pulmonary epithelioid hemangioendothelioma were retrospectively collected. All cases were admitted to Fujian Medical University Union Hospital from January 2012 to May 2023.Results:Of 7 PEHE cases, 2 underwent tumor biopsy and 5 underwent tumor resection. There were 4 males and 3 females, with a median age of 58 years old. Six cases showed multiple bilateral nodules, and only one case showed a single lesion in the lower left lung lobe. Five patients presented with respiratory symptoms, like cough, sputum, hemoptysis, shortness of breath. There were round-like solid lesions with clear border and homogeneous density on lung CT. Histologically, it showed nodular growth with a distinctive myxohyaline stroma. Necrosis was seen in the center of some cases. Epithelioid tumor cells were arranged in cords, solid pattern or single cells, with abundant eosinophilic cytoplasm and occasional intracytoplasmic vacuoles. The plasmacytoid nucleus were round to oval in shape with obvious nucleoli, minimal pleomorphism and few mitoses. The tumor cells were positive for vascular endothelial markers: CD31 (7/7), CD34 (5/7), ERG (6/6), and Fli-1 (5/6); CKpan was focally positive in 3 cases (3/7), and TFE3 in 2 cases. Ki-67 index ranged from 5% to 10%. Additionally, the tumor cells partially express PD-L1 in two cases. Moreover, lung carcinoma-related gene detection was negative in one case. The TFE3 break-apart probe in two cases did not display a split signal. In terms of treatment, 4 cases were treated with surgery, 1 case was treated with chemotherapy and surgery, and 2 cases were follow-up observation. After the median 34.4 months follow-up time, one was lost to follow-up, six were survived. Their CT scans showed slight enlargement of pulmonary nodules without other organ metastases.Conclusions:PEHE is a rare vascular-derived tumor, which is usually characterized by multiple solid bilateral nodules with slow growth. It tends to lack specific clinical symptoms, and is prone to be misdiagnosed as a metastatic carcinoma. Diagnosis primarily rely on pathology, with the use of an immunohistochemical package being crucial for definitive and differential diagnosis.

Objective:To investigate the impact of Wenyang Ligong Decoction on pregnancy outcomes after transcervical resection of adhesions (TCRA) in patients with intrauterine adhesions (IUA).Methods:A retrospective cohort study was conducted to collect clinical data from 151 patients with IUA who underwent TCRA in the Reproductive Medicine Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between January 2020 and January 2023. Patients were divided into a Traditional Chinese medicine (TCM) group (79 patients) and a control group (72 patients) based on whether they received Wenyang Ligong Decoction after TCRA. The TCM group received estrogen and progesterone sequential therapy post-surgery, combined with Wenyang Ligong Decoction for 2-3 menstrual cycles. The control only received sequential treatment with estrogen and progesterone.Pregnancy outcomes one year after surgery were compared between the two groups. After adjusting for confounding factors using multivariate Cox regression analysis, the effect of Wenyang Ligong Decoction on pregnancy outcomes after TCRA in patients with IUA was observed.Results:The live birth rate [54.43%　(43/79)], the ongoing pregnancy rate [56.96% (45/79)], and the clinical pregnancy rate [52.03% (49/79)] were higher in the TCM group than in the control [26.39% (19/72), P<0.001; 30.56% (22/72), P=0.001;37.50% (27/72), P=0.003], with statistically significant differences. There were no statistically significant differences in early abortion rate and late abortion rate between the TCM group and the control (all P>0.05). According to the stratified analysis by preparation methods, in the natural conception group, the live birth rate [60.78% (31/51)], the ongoing pregnancy rate [62.75% (32/51)], and the clinical pregnancy rate [68.63% (35/51)] in the TCM group were significantly higher than those in control group [21.43% (12/56), P<0.001; 26.79% (15/56), P<0.001; 33.93% (19/56), P<0.001]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05). In the assisted reproductive technology group, there were no statistically significant differences in live birth rate, ongoing pregnancy rate, clinical pregnancy rate, early miscarriage rate, and late miscarriage rate between the two groups (all P>0.05). According to the stratified analysis by age, in the <35-year-old patients, the live birth rate [66.00% (33/50)], the ongoing pregnancy rate [70.00% (35/50)], and the clinical pregnancy rate [74.00% (37/50)] in the TCM group were significantly higher than those in control group [41.30% (19/46), P=0.015; 47.83% (22/46), P=0.027; 54.35% (25/46), P=0.044]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05). In the ≥35-year-old patients, the live birth rate [34.48% (10/29)], the ongoing pregnancy rate [34.48% (10/29)], and the clinical pregnancy rate [41.38% (12/29)] in the TCM group were significantly higher than those in control group [0%, P=0.001; 0%, P=0.001; 7.69% (2/26), P=0.004]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05).Univariate Cox regression analysis showed that age, number of previous uterine cavity interventions, IUA score, degree of IUA, and endometrial thickness after TCRA were independent risk factors for live births, and age, IUA score, degree of IUA, intima thickness after TCRA, and treatment group were the influencing factors of persistent pregnancy (all P<0.05). After adjusting for confounding factors, multivariate Cox regression analysis showed that Wenyang Ligong Decoction significantly improved the live birth rate ( HR=3.19, 95% CI: 1.77-8.11, P=0.001) and the rate of continuous pregnancy ( HR=3.66, 95% CI: 1.80-7.48, P<0.001) in patients with IUA. Conclusion:Wenyang Ligong Decoction can significantly improve pregnancy outcomes after TCRA in patients with IUA.

With advancements in in vitro culture techniques, the morula has emerged as a promising candidate for selective embryo transfer due to its critical compaction phase. The compaction process involves not only structural reorganization but also complex intercellular signaling mechanisms that significantly influence embryonic developmental potential and cellular fate determination. Clinical data reveal comparable live birth rates between day 4 morula transfers and day 5 blastocyst transfers, coupled with reduced in vitro culture duration. However, challenges persist regarding standardized evaluation criteria and long-term safety confirmation. Current morphological assessment methods exhibit inherent subjectivity, while emerging technologies integrating genetic screening, metabolic analysis, and time-lapse imaging show potential for enhanced selection accuracy. Personalized synchronization assessments, including endometrial receptivity analysis, may further optimize transfer protocols. This study focuses on day 4 embryo transfer, systematically reviewing its embryonic development processes, evaluation protocols, comparative outcomes of transferred embryos, and research advances in frozen-thawed embryo transfer. The study aims to deepen scientific understanding of day 4 embryo transfer and promote its adoption as a critical option in personalized reproductive medicine, thereby enhancing clinical success rates and safety.