OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

Objective: To understand the awareness of chikungunya fever knowledge and its related factors among medical college students in Baise City, so as to provide a scientific basis to offer relevant courses and special education. Methods: From July to August 2025, 7 286 enrolled medical students were selected by a sampling method from a medical college in Baise City to participate in the questionnaire survey. The questionnaire covered epidemiological characteristics, clinical symptoms, and prevention/control knowledge of chikungunya fever. Statistical analyses including the Chi quare test and multivariate Logistic regression models were performed. Results: The overall awareness rate of chikungunya fever knowledge among the medical students was 18.89%. Among the knowledge items, the awareness rate of "the high incidence season" was the highest (84.05%), while that of "the infectious period" was the lowest (17.80%). Multivariate Logistic regression analysis showed that medical students with female (a OR= 1.37 , 95%CI =1.20- 1.57 ), the age for over 25 years old (a OR=1.76, 95%CI =1.05-2.93), whose father had a middle school educational level (a OR=1.18, 95%CI =1.05-1.31), and majored in preventive medicine (a OR=1.54, 95%CI =1.10-1.67) had relatively higher awareness rates of chikungunya fever knowledge (all P <0.05). In contrast, students of Zhuang ethnicity (a OR= 0.87 , 95%CI =0.76-0.98) and majoring in nursing (a OR=0.74, 95%CI =0.61-0.91) or pharmacy (a OR=0.70, 95%CI =0.52-0.95) had relatively lower awareness rates (all P <0.05). Conclusions The awareness rate of chikungunya fever related knowledge among medical college students in Baise City is relatively low. Schools should take targeted publicity measures to improve medical students awareness.

ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.

Accommodative dysfunction, particularly accommodative lag, acts as a core hub connecting near work activity to myopic axial elongation. This review thoroughly explores the multidimensional biological mechanisms by which accommodative function drives axial growth. In addition to the classic pathway where hyperopic defocus signals induce retinal-choroidal-scleral biochemical remodeling, two other mechanisms are highlighted: a biomechanical pathway involving direct mechanical traction on the equatorial sclera caused by sustained ciliary muscle contraction, and a neural pathway where abnormal accommodative micro fluctuations degrade retinal image quality, thereby triggering abnormal ocular growth. Based on these comprehensive mechanisms, this paper systematically analyzes the principles of pharmacological(atropine), optical(orthokeratology, defocus lenses), and vision therapy interventions. Myopia progression results from the integrated regulation of optical defocus, mechanical stress, and neural dynamics. Future myopia control should advance toward precise, personalized combination strategies tailored to individual accommodative and genetic profiles.

Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology* ; Humans ; Osteosarcoma/pathology* ; Tumor Microenvironment ; Sarcoma, Ewing/pathology* ; Chondrosarcoma/pathology* ; Animals ; Cell Culture Techniques/methods* ; Cell Culture Techniques, Three Dimensional/methods* ; Cell Line, Tumor

OBJECTIVE: Coptis chinensis (Huanglian in Chinese, HL) is commonly utilized in clinical settings to counteract dyslipidemia in patients with hot syndrome. Its lipid-reducing efficacy has been consistently demonstrated in high-fat diet (HFD)-induced hyperlipidemic animal models. However, whether HL's efficacy differs in HFD-fed animals with hot or cold syndromes remains unclear. This study aims to discern the variations in the anti-hyperlipidemic effects of HL in HFD-fed mice with hot or cold syndromes. METHODS: HFD-induced C57BL/6 mice were subjected to cold or hot syndrome via two weeks of ice water (0 °C) and levothyroxine sodium (240 µg/kg) treatment, respectively. Then, an aqueous extract of HL was administered to the mice via oral gavage over the following four-week period. Lipid levels in the serum and liver were gauged to determine the lipid-reducing effects of HL. Furthermore, gut microbiota composition was elucidated using full-length 16S rRNA gene sequencing. RESULTS: HL notably reduced lipid levels in HFD-induced hyperlipidemic mice. Its efficacy was amplified in hyperlipidemic mice with a hot syndrome but was markedly reduced in those with a cold syndrome. HL treatment led to a decline in alpha-diversity (characterized by ACE, Chao1, Shannon and Simpson index) of the gut microbiota in both sets of mice but affected specific microbial populations based on the syndrome. Specifically, while HL led to a notable increase in Eubacterium, Robinsoniella, and Lachnoclostridium genera, along with the enhancement of Clostridium innocuum and Bacteroides thetaiotaomicron species across all conditions, it syndrome-dependently stimulated Romboutsia ilealis and Parabaceroides_sp_HGS0025 species in mice with hot syndrome. CONCLUSION HL shows stronger lipid-lowering effect on hyperlipidemic mice with hot syndrome, which is in accordance with its traditional usage in clinic. The therapeutic outcomes of HL are intrinsically tied, at least in part, to its modulatory effects on the gut microbiota, offering fresh insights into the foundational principles of traditional Chinese medicine.

Bombyx mori nucleopolyhedrovirus (BmNPV) is extremely harmful to the silk industry. The polyhedrin, which encodes the polyhedrin (Polh), can be expressed at ultra-high levels and form occlusion bodies in the nucleus, embedding the progeny virus within it. However, the detailed mechanism by which polyhedrin is transported into the host cell nucleus remains unknown. Clarifying the nuclear import mechanisms of viral proteins can help us develop better prevention and treatment measures against baculoviruses. This study employed molecular cloning, co-immunoprecipitation, and immunofluorescence to analyze in detail the expression pattern of the highly expressed polyhedrin in the very late stage of the virus, and further revealed that the host protein importin α participates in the nuclear import of polyhedrin through protein interactions. This study provides a reference for further elucidating the nuclear import mechanisms of the baculovirus proteins including polyhedrin that can enter the nucleus.
Nucleopolyhedroviruses/metabolism* ; Active Transport, Cell Nucleus ; Animals ; Bombyx/virology* ; alpha Karyopherins/metabolism* ; Cell Nucleus/metabolism* ; Viral Structural Proteins/metabolism* ; Occlusion Body Matrix Proteins

Objective:This study aimed to systematically evaluate the efficacy of glucagon-like peptide-1(GLP-1) receptor agonists and multi-target analogs on weight reduction and cardiometabolic outcomes in non-diabetic individuals with obesity, and to compare the efficacy and safety across different GLP-1 receptor agonists.Methods:Randomized controlled trials(RCTs) published between January 2000 and March 2025 were identified through a systematic search of CNKI, Wanfang, Web of Science, PubMed, and Cochrane databases. Two reviewers independently screened the studies, extracted data, and assessed methodological quality. Meta-analysis was performed using RevMan 5.4.1 software. Results:A total of 16 RCTs involving 11 032 non-diabetic individuals with obesity were included. Meta-analysis showed that GLP-1 receptor agonists significantly reduced body weight(ΔWeight=-8.71 kg, 95% CI -10.68 to -6.74, P<0.001) and BMI(ΔBMI=-3.01 kg/m 2, 95% CI -3.77 to -2.25, P<0.001), as well as improved systolic blood pressure(ΔSBP=-4.13 mmHg, 1 mmHg=0.133 kPa, 95% CI -4.87 to -3.39, I2=60%) and diastolic blood pressure(ΔDBP=-1.39 mmHg, 95% CI -2.32 to -0.46, I2=95%). Tirzepatide showed the most pronounced effects on both weight and blood pressure reduction. In addition, GLP-1 receptor agonists significantly lowered LDL-C, TC, and TG, while moderately increasing HDL-C levels. In terms of safety, GLP-1 receptor agonists were associated with an increased risk of gastrointestinal adverse events, but did not significantly increase the risk of hypoglycemia. Conclusion:GLP-1 receptor agonists are effective in reducing weight, BMI, and blood pressure, and in improving lipid profiles in non-diabetic individuals with obesity. However, gastrointestinal side effects should be closely monitored. Given the variability in efficacy and safety among various GLP-1 receptor agonists, personalized treatment approaches are recommended.

Objective:To explore the surgical strategies and clinical efficacy of open partial nephrectomy in the treatment of renal angiomyolipoma (AML) with inferior vena cava tumor thrombus.Methods:A retrospective analysis was conducted on the clinical data of 5 patients with renal AML and inferior vena cava tumor thrombus who underwent partial nephrectomy at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to December 2022. There were 2 male and 3 female patients, with a median age of 37 years, ranged from 33 to 45 years. All patients were identified during routine physical examinations. Four patients presented with right-sided lesions, while one had a left-sided lesion. The diameter of the primary tumor within the kidney ranged from 3.0 to 7.0 cm, with a median diameter of 5.5 cm.The length of the tumor thrombus within the inferior vena cava ranged from 1.0 to 6.0 cm, with a median length of 1.5 cm. Among them, 2 patients underwent laparoscopic nephrectomy combined with extracorporeal workbench tumor resection and autologous kidney transplantation (the workbench surgery group), while 3 patients underwent open in-situ partial nephrectomy combined with removal of inferior vena cava tumor thrombus (the in-situ nephron-sparing surgery group). The surgical method of the workbench surgery group: The patients first underwent laparoscopic nephrectomy on the affected side combined with inferior vena cava tumor thrombus removal, then the incision was extended to remove the affected kidney, and table partial nephrectomy was performed. After completely removing the tumor and tumor thrombus within the affected kidney and renal vein, autologous kidney transplantation was performed in the iliac fossa. The surgical method of the in-situ kidney preservation surgery group: The affected kidney, renal artery and vein on the affected side, inferior vena cava, and contralateral renal vein were dissected and exposed. The distal end of the inferior vena cava, the contralateral renal vein, the proximal end of the inferior vena cava, and the renal artery on the affected side were blocked respectively. The venous wall was opened in the middle of the renal vein, and the tumor thrombus was gradually pulled out. According to the pre-marked tumor boundary, the tumor within the kidney was gradually removed by alternate blunt and sharp dissection combined with suction, and the wound surface was sutured layer by layer. The perioperative conditions, complications, and follow-up results of the patients were analyzed.Results:All 5 surgeries were successfully completed, with a median operation time of 100 to 450 minutes and a median operation time of 200 minutes. The intraoperative bleeding volume was 100 to 600 ml, with the median of 150 ml. In the in-situ nephron-sparing surgery group, the renal artery occlusion time was 28 to 41 minutes, and the median occlusion time was 34 minutes. All patients were discharged safely after surgery, and there were no serious perioperative complications. The postoperative pathology of all 5 patients was renal angiomyolipoma, without any epithelioid components. The patients were followed up for 12 to 90 months, with a median follow-up duration of 24 months. None of the 5 patients had tumor recurrence or metastasis, and no patient developed chronic kidney dysfunction during follow-ups.Conclusions:Renal AML with venous tumor thrombus is a challenging clinical problem. In situ open partial nephrectomy or the combined approach through the workbench and autologous kidney transplantation can effectively remove the tumor thrombus and maximize the protection of renal function. For cases of ① multiple or complex renal AML; ② complex vascular system structure within the renal sinus requiring precise anatomy; ③ renal AML with a previous history of hemorrhage, complex adhesions around, and difficult dissociation, table partial nephrectomy combined with inferior vena cava tumor thrombus removal and autologous kidney transplantation can be selected. For cases where the expected surgical operation is simple, in situ open partial nephrectomy can significantly shorten the operation time and reduce surgical trauma.

Objective:To investigate the relationship between the BCL2 family protein BIM and ibrutinib resistance in chronic lymphocytic leukemia (CLL) and to analyze its regulatory mechanisms on apoptosis and autophagy.Methods:RNA sequencing (RNA-seq) was used to examine changes in the expression of BCL2 family proteins in samples from patients with CLL, MEC1 cell lines, and ibrutinib-resistant cell lines (MR). Western blot was used to analyze changes in BIM protein expression during apoptosis in MR. shRNA knockdown was used to assess the effects of BIM on cell proliferation and apoptosis. RNA-seq and the autophagy inhibitor chloroquine treatment were used to study autophagy-related changes in MR.Results:BIM expression was significantly downregulated before and after drug resistance in CLL primary cells and MEC1 cell lines ( P<0.0001). Knockdown of BIM in CLL cells inhibited ibrutinib-induced apoptosis and promoted cell proliferation ( P<0.05 for both). In addition, protective autophagy was increased in MR and apoptosis was increased after administration of chloroquine and small interfering RNA. The increased expression of LC3-Ⅱ protein in BIM-knockdown cell lines ( P<0.01) suggested that reduction of BIM may mediate autophagy activation. Conclusion:Downregulation of BIM may be a key factor in promoting ibrutinib resistance in CLL by activating protective autophagy. These findings provided a potential target for improving CLL treatment.