ObjectiveTo investigate the effect of Zishen Huoxue Formula （ZSXHF） on molecular-targeted therapy-associated proteinuria in patients with primary liver cancer （PLC）， to assess the efficacy of ZSXHF in the treatment of molecular-targeted therapy-associated proteinuria， and to provide a basis for clinical medication. MethodsA retrospective cohort study was conducted among the PLC patients with molecular-targeted therapy-associated proteinuria who were diagnosed and treated in The Department of Hepatology of Chinese PLA General Hospital， from January 1， 2022 to July 1， 2025. With ZSXHF treatment as the exposure factor， the patients with a cumulative treatment duration of ≥9 weeks were enrolled as traditional Chinese medicine （TCM） group， while those without TCM treatment were enrolled as control group. Propensity score matching was performed for the two groups at a ratio of 1∶1 based on sex， age， 24-hour urinary protein， blood urea nitrogen， and serum creatinine. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for promoting the improvement of targeted-therapy-associated proteinuria. ResultsA total of 137 PLC patients with targeted-therapy-associated proteinuria were enrolled， with 34 patients in the TCM group and 103 in the control group. After follow-up for 6 months， the TCM group had a significant improvement in urinary protein grade compared with the control group （χ²=9.261， P=0.016）. There were 25 patients in each group after propensity score matching， and after follow-up for 6 months， there were significant differences between the two groups in urinary protein grade （χ²=15.689， P<0.001） and 24-hour urinary protein （Z=-3.075， P=0.002）. After cumulative treatment with ZSXHF for ≥9 weeks， the TCM group had a significantly greater change in 24-hour urinary protein from baseline compared with the control group （t=-2.514， P=0.016）， while there were no significant differences in the changes in liver and renal function after ZSXHF intervention between the two groups （all P>0.05）. The multivariate Logistic regression analysis showed that ZSXHF treatment （odds ratio=2.901， 95% confidence interval： 1.135 — 7.417， P=0.026） was an independent influencing factor for improvement in molecular-targeted therapy-associated proteinuria. ConclusionZSHXF can effectively alleviate molecular-targeted therapy-associated proteinuria in PLC patients with a favorable safety profile， which provides a new reference for TCM prevention and treatment of molecular-targeted therapy-associated adverse reactions in PLC patients.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveStroke remains the leading cause of acquired disability in adults worldwide, imposing a substantial socioeconomic burden on patients, families, and healthcare systems. Among the various neurological deficits caused by stroke, motor dysfunction——particularly contralateral hemiplegia——is the most common and debilitating consequence, and it predominantly results from damage to the cortical motor conduction pathways. When motor cortex neurons or their projecting fibers are damaged, the distal axons and their associated myelin sheaths undergo a series of progressive, programmed degeneration, fragmentation, and eventual phagocytic clearance. This pathological process is termed Wallerian degeneration (WD). However, the temporal progression of WD following ischemic stroke and the associated alterations in the local glial microenvironment remain incompletely understood. The present study was designed to systematically elucidate the time course of corticospinal tract (CST) axonal WD after ischemic stroke in mice, and to simultaneously characterize the dynamic pathological changes of astrocytes, microglia, oligodendrocyte lineage cells, and myelinating oligodendrocytes during the WD process. MethodsEight-week-old male C57BL/6J mice were randomly assigned to control and ischemic stroke groups. A focal cortical ischemic stroke model was established in the right sensorimotor cortex using the photothrombotic method. This method induces localized intravascular thrombosis in the target cortical region through precisely controlled interaction between the photosensitizer and laser light of specific wavelength. At day 1 post‑surgery, 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate infarct volume, hematoxylin and eosin (HE) staining for histopathological examination, and Nissl staining for assessment of neuronal injury. For axonal degeneration time-course analysis, rAAV-CAG-mCherry anterograde viral tracing was employed to specifically label CST neurons. Cervical spinal cord sections at the CST region were collected at day 3, 5, 7, 14, and 60 post-injury. Morphological changes of mCherry-positive CST fibers were observed under fluorescence microscopy, and the fluorescence signal area fraction within the defined region was quantitatively analyzed to evaluate the dynamic process of axonal degeneration. For glial response assessment, immunofluorescence staining against Iba1 (microglia), GFAP (astrocytes), Olig2 (oligodendrocyte lineage cells), and APC (myelinating oligodendrocytes) was performed at day 7, 14, and 60 post‑surgery. The numbers of positive cells were counted to quantitatively analyze the dynamic changes in each glial population at different time points after ischemia, thereby revealing the evolution of the glial microenvironment during WD. ResultsThe photothrombotic method stably and reliably established an ischemic brain injury model confined to the sensorimotor cortex. Viral tracing revealed that the proportion of mCherry‑positive CST fibers was significantly reduced at day 7 after ischemic injury to the neuronal soma. Immunofluorescence staining demonstrated that during WD, the numbers of microglia and astrocytes in the CST region were significantly increased, whereas the numbers of oligodendrocyte lineage cells and myelinating oligodendrocytes showed no significant changes. ConclusionWD of CST axons is observed at day 7 post-ischemic stroke in a delayed manner. This degenerative process selectively activates microglia and astrocytes, while leaving the number of oligodendrocyte lineage cells largely unaffected.

BACKGROUND:At present,research has only shown that the cervical lordosis ratio can be an important factor in predicting the loss of lordosis curvature after laminoplasty,and no one has studied whether the cervical lordosis ratio,a dynamic level indicator,can be one of the decision-making factors for the selection of posterior cervical surgical procedures. OBJECTIVE:To investigate whether the cervical lordosis ratio,an index of cervical hyperextension and hyperflexion,can be used as a selective index for laminoplasty and laminectomy fusion. METHODS:A retrospective review of 141 patients who had undergone posterior cervical surgery more than one year of follow-up due to multi-level cervical spondylotic myelopathy from December 2015 to March 2020 was performed.Among them,63 patients received laminectomy and fusion(laminectomy and fusion group)and 78 patients received laminoplasty(laminoplasty group).The demographic statistics(gender,age,body mass index,follow-up time),imaging indexes such as C2-7 Cobb angle,C2-7 range of motion,flexion Cobb angle,extension Cobb angle,flexion range of motion and extension range of motion,clinical effect indexes such as Japanese Orthopaedic Association score and visual analog scale score were compared between the two groups.The evaluation index of cervical lordosis alignment change was C2-7 Cobb angle difference before and after operation(ΔCL).Cervical lordosis ratio was equal to 100%×flexion range of motion/C2-7 range of motion.Receiver operating characteristic curve analysis was used to determine the role of cervical lordosis ratio in predicting postoperative severe cervical lordosis loss(ΔCL≤-10°).According to the critical value of cervical lordosis ratio(68.5%),all patients were divided into low cervical lordosis ratio group and high cervical lordosis ratio group.In these two ratio groups,the cervical lordosis alignment index and clinical effect index between the two operation groups were discussed again. RESULTS AND CONCLUSION:(1)Cervical lordosis alignment decreased after laminectomy and fusion and laminoplasty(P=0.039,P=0.002),and cervical lordosis alignment change in laminoplasty group(ΔCL)was greater than that of laminectomy and fusion group,and the difference between the two groups was statistically significant.(2)Based on receiver operating characteristic curve analysis,cervical lordosis ratio in predicting severe cervical lordosis alignment change(ΔCL≤-10°)had good identification ability(area under the curve=0.792).(3)In low cervical lordosis ratio group,there was no significant difference in cervical lordosis alignment change(ΔCL)between laminectomy and fusion group and laminoplasty group(P=0.141).(4)In high cervical lordosis ratio group,the ΔCL of laminoplasty group was greater than that in laminectomy and fusion group(P=0.001),which had a higher probability of postoperative severe cervical lordosis alignment change(ΔCL≤-10°)(43%,29%).(5)It is indicated that cervical lordosis ratio can be used as a decision-making index for the choice of posterior surgery for multi-level cervical spondylotic myelopathy.Laminoplasty can be considered in the low cervical lordosis ratio group,while laminectomy and fusion can be considered in the high cervical lordosis ratio group.

BACKGROUND:More and more animal experiments and clinical studies have confirmed that electrical stimulation can promote the repair of peripheral nerve injury,but the specific mechanism is not yet fully understood. OBJECTIVE:To investigate the effect of electrical stimulation-induced miR-741-3p regulating Radil on Schwann cell migration. METHODS:(1)Twelve male SD rats were randomly divided into electrical stimulation group and control group.The electrical stimulation group received continuous electrical stimulation for 7 days after sciatic nerve compression injury,while the control group was not treated after sciatic nerve compression.The injured nerves were taken on day 7 after operation.The expression difference of miR-741-3p between the two groups was verified by fluorescence in situ hybridization.(2)The target genes of miR-741-3p were predicted by miRDB,TargetScan,and miRWalk databases.(3)Schwann cells were transfected with miR-741-3p mimetic and its control,miR-741-3p inhibitor and its control,Radil siRNA and its control,miR-741-3p inhibitor+Radil siRNA and miR-741-3p inhibitor+siRNA control.The transfection efficiency was detected by RT-PCR.The migration ability of Schwann cells was detected by Transwell chamber. RESULTS AND CONCLUSION:(1)The fluorescence intensity of miR-741-3p in the electrical stimulation group was lower than that in the control group.(2)The results of database prediction showed that 69 genes might be the target genes of miR-741-3p.Radil was one of the predicted target genes,which was mainly involved in cell adhesion and migration.(3)Compared with the miR-741-3p inhibitor control group,the number of Schwann cell migration increased in the miR-741-3p inhibitor group(P<0.05).Compared with the miR-741-3p mimic control group,the number of Schwann cell migration in the miR-741-3p mimic group decreased(P<0.05).Compared with the siRNA control group,the number of Schwann cell migration was decreased in the Radil siRNA group(P<0.05).(4)Compared with miR-741-3p inhibitor control group,the expression level of Radil was increased in miR-741-3p inhibitor group.Compared with miR-741-3p mimic control group,the expression level of Radil was decreased in miR-741-3p mimic group.(5)Compared with miR-741-3p inhibitor+siRNA control group,the number of Schwann cell migration was reduced in miR-741-3p inhibitor+Radil siRNA group(P<0.05).The results showed that electrical stimulation promoted the migration of Schwann cells by down-regulating miR-741-3p and targeting Radil gene.

In order to clarify the effects of drought stress training on the quality and drought resistance of Codonopsis pilosula, this study used PEG to simulate drought stress and employed potting with water control for the drought stress training of C. pilosula plants. The polysaccharide content, secondary metabolites, antioxidant system, and photosynthetic pigment system of C. pilosula after drought stress training were analyzed. The results showed that the content of fructans in the root of C. pilosula increased after two rounds of drought stress treatment, and it was significantly higher than that of the control group. The accumulation of fructans in the root of C. pilosula showed an upward trend during the rehydration treatment. The content of lobetyolin and tangshenoside Ⅰ increased after drought stress treatment compared with that of the control group. The rehydration treatment caused first increasing and then decreasing in the content of lobetyolin, while it had no significant effect on the tangshenoside Ⅰcontent. The content of photosynthetic pigments decreased after drought stress treatment, and it gradually increased during the first round of rehydration and the second round of rehydration. Moreover, the increase was faster in the second round of rehydration than in the first round of rehydration. The content of the peroxidation product malondialdehyde(MDA) and the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) increased after drought stress treatment compared with those of the control group, and they showed a tendency of decreasing during rehydration. Moreover, the decrease was faster in the second round of rehydration than in the first round of rehydration. When the plants of C. pilosula after drought stress training were again subjected to severe drought stress, the wilting rate decreased significantly, and the biomass increases significantly. This study showed that the drought stress training could promote the accumulation of polysaccharides and secondary metabolites in the root of C. pilosula. When encountering drought stress again, C. pilosula plants could quickly regulate the antioxidant system and delay the decomposition of chlorophyll to respond to drought stress. The findings provide a theoretical basis for the ecological cultivation of C. pilosula in arid and semi-arid areas.
Codonopsis/growth & development* ; Droughts ; Polysaccharides/metabolism* ; Stress, Physiological ; Water/metabolism* ; Antioxidants/metabolism* ; Photosynthesis ; Drought Resistance

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

The purpose of this study was to clarify the effect of Huotan Jiedu Tongluo Decoction on atherosclerosis(AS) injury in ApoE~(-/-) mice by regulating the ferroptosis pathway. Seventy-five ApoE~(-/-) mice were randomly divided into model group, low-, medium-, and high-dose of Huotan Jiedu Tongluo Decoction groups, and evolocumab group(n=15), and 15 C57BL/6J mice were selected as the blank group. Mice in the blank group were fed with a normal diet, and those in the other groups were fed with a high-fat diet to induce AS. From the 9th week, mice in Huotan Jiedu Tongluo Decoction groups were administrated with Huotan Jiedu Tongluo Decoction at corresponding doses by gavage, and those in the blank group and the model group were given an equal volume of distilled water. Mice in the evolocumab group were treated with evolocumab 18.2 mg·kg~(-1 )by subcutaneous injection every 2 weeks. After 8 weeks of continuous intervention, oil red O staining and hematoxylin-eosin(HE) staining were employed to observe the lipid deposition and plaque formation in the aortic root. Masson staining was used to evaluate the collagen content in the aortic root. The serum levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were determined by biochemical kits. The levels of Fe~(2+), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the aorta were measured by colorimetry. The protein and mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), and acyl-CoA synthetase long chain family member 4(ACSL4) in the aorta were detected by Western blot and RT-qPCR, respectively. The expression of Nrf2, GPX4, and SLC7A11 was localized by immunofluorescence. The results showed that low-, medium-, and high-dose Huotan Jiedu Tongluo Decoction reduced the plaque formation of aortic root and increased the collagen content in AS mice. At the same time, Huotan Jiedu Tongluo Decoction improved the lipid metabolism by lowering the levels of TC, LDL-C, and TG and elevating the level of HDL-C in the serum. Huotan Jiedu Tongluo Decoction enhanced the antioxidant capacity by elevating the levels of GSH and SOD and lowering the level of MDA in the aorta and inhibiting the accumulation of Fe~(2+) in the aorta. In addition, Huotan Jiedu Tongluo Decoction up-regulated the protein and mRNA levels of Nrf2, GPX4, and SLC7A11, while down-regulating the protein and mRNA levels of ACSL4. In summary, Huotan Jiedu Tongluo Decoction can effectively alleviate AS lesions in ApoE~(-/-) mice by activating the Nrf2/GPX4 pathway, reducing lipid peroxidation, and inhibiting ferroptosis.
Animals ; Ferroptosis/drug effects* ; Atherosclerosis/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/genetics* ; Mice ; Mice, Inbred C57BL ; Apolipoproteins E/metabolism* ; Male ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Signal Transduction/drug effects* ; Humans ; Mice, Knockout

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

The health of women and children serves as the cornerstone of comprehensive public health and represents a crucial barometer for measuring social progress and civilization. It directly impacts family well-being and social harmony. As a national-level guidance center for complex disease diagnosis and treatment, Beijing's critical maternal care center, and the designated consultation hospital for pregnancy complicated by rheumatic immune and endocrine disorders, Peking Union Medical College Hospital bears significant responsibilities in managing complex medical cases and implementing counterpart assistance programs. Confronted with diverse and complicated maternal sources, particularly emergency cases lacking standardized prenatal care, the hospital has established a multi-tiered, whole-process, and comprehensive maternal-infant safety management system. Through implementing high-risk maternal management protocols, optimizing critical care procedures, promoting informatization development, and enhancing multidisciplinary collaboration, Peking Union Medical College Hospital has substantially improved the efficiency of critical maternal care and maternal-infant safety assurance. This paper systematically summarizes the institutional development experience in maternal management and explores potential optimization approaches, aiming to provide valuable references for enhancing maternal-infant safety management systems in domestic healthcare institutions.