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.

Objective To explore the clinical efficacy and medical costs of high ligation and stripping of the great saphenous vein,simple foam sclerotherapy,and high ligation of the great saphenous vein combined with foam sclerotherapy for treating varicose of great saphenous vein.Methods The clinical data of patients with varicose of great saphenous vein undergoing high ligation and stripping of the great saphenous vein,simple foam sclerotherapy,or high ligation of the great saphenous vein combined with foam sclerotherapy were analyzed retrospectively.The evaluation included efficacy assessment,quality of life evaluation,hospitalization days and costs,postoperative complications,and recurrence after surgery.Results There were no statistical differences in gender,age,disease course and clinical etiology anatomy pathophysiology(CEAP)grading system among the three groups(P＞0.05).The clinical efficacy assessments in all patients among the three groups showed significant effects at 3 and 6 months postoperatively.One patient in the group treated with high ligation of the great saphenous vein combined with foam sclerotherapy suffered deep vein thrombosis of lower extremity after operation.In terms of quality of life,there was no statistically significant difference in venous clinical severity score(VCSS)among the three groups at 3 months postoperatively(P＞0.05).The group treated with simple foam sclerotherapy showed significantly shorter hospitalization days compared with the other two groups.Additionally,the group treated with simple foam sclerotherapy showed lower hospitalization expenses,which was not statistically significant when compared to the group treated with high ligation and stripping of the great saphenous vein group(P＞0.05),but there was a statistical difference compared to the group treated with high ligation of the great saphenous vein combined with foam sclerotherapy(P＜0.05).Conclusion There are no significant differences in clinical efficacy,postoperative pain,and quality of life evaluation among the three methods.However,simple foam scle-rotherapy may reduce the length of hospitalization stay and direct medical costs.

This article reported a case of generalized arterial calcification in infancy (GACI), which was suspected prenatally and confirmed postnatally. At 24 weeks of gestation, a systematic ultrasound revealed aortic wall thickening with hyperechogenicity, a thickened mitral valve accompanied by hyperechoic changes, thickened and calcified tricuspid valves, and multiple hyperechoic foci in both ventricles. A follow-up echocardiography at 28 weeks showed no significant progression. Emergency cesarean section was performed at 31 weeks due to fetal distress. Postnatal echocardiography confirmed generalized arterial calcification. Whole-exome trio sequencing identified two variants in the ENPP1 gene: c.1274-2A>G and c.1437+3(IVS14)_c.1437+6(IVS14)delGAGT. Based on imaging, laboratory results, and genetic testing, the infant was diagnosed with GACI type 1, concomitant with autosomal recessive hypophosphatemic rickets type 2. Given the poor prognosis, the family withdrew from further medical intervention.

To clarify the species, pathogenicity, and distribution of the pathogens causing the root rot of Atractylodes lancea in Hubei province, the tissue separation method was used to isolate the pathogens from root rot samples in the main planting areas of A. lancea in Hubei. Based on the preliminary identification of the Fusarium genus by the internal transcribed spacer(ITS) sequence, three housekeeping genes, EF1/EF2, Btu-F-FO1/Btu-F-RO1, and FF1/FR1, were amplified and sequenced. Subsequently, a phylogenetic tree was constructed based on these TEF gene sequences to classify the pathogens. The pathogenicity of these strains was determined using the root irrigation method. A total of 194 pathogen strains were isolated using the tissue separation method. Molecular identification using the three housekeeping genes identified the pathogens as F. solani, F. oxysporum, F. commune, F. equiseti, F. tricinctum, F. redolens, F. fujikuroi, F. avenaceum, F. acuminatum, and F. incarnatum. Among them, F. solani and F. oxysporum were the dominant strains, widely distributed in multiple regions, with F. solani accounting for approximately 54% of the total isolated strains and F. oxysporum accounting for approximately 34%. Other strains accounted for a relatively small proportion, totaling approximately 12%. The results of pathogenicity determination showed that there were certain differences in pathogenicity among strains. The analysis of the pathogenicity differentiation of the widely distributed F. solani and F. oxysporum strains revealed that these dominant strains in Hubei were mainly highly pathogenic. This study determined the species, pathogenicity, and distribution of the pathogens causing the root rot of A. lancea in Hubei province. The results provide a scientific basis for further understanding the root rot of A. lancea and its epidemic occurrence and scientifically preventing and controlling this disease.
Plant Diseases/microbiology* ; Atractylodes/microbiology* ; Phylogeny ; Plant Roots/microbiology* ; Fusarium/classification* ; China ; Virulence ; Fungal Proteins/genetics*

Objective To explore the clinical efficacy and medical costs of high ligation and stripping of the great saphenous vein,simple foam sclerotherapy,and high ligation of the great saphenous vein combined with foam sclerotherapy for treating varicose of great saphenous vein.Methods The clinical data of patients with varicose of great saphenous vein undergoing high ligation and stripping of the great saphenous vein,simple foam sclerotherapy,or high ligation of the great saphenous vein combined with foam sclerotherapy were analyzed retrospectively.The evaluation included efficacy assessment,quality of life evaluation,hospitalization days and costs,postoperative complications,and recurrence after surgery.Results There were no statistical differences in gender,age,disease course and clinical etiology anatomy pathophysiology(CEAP)grading system among the three groups(P＞0.05).The clinical efficacy assessments in all patients among the three groups showed significant effects at 3 and 6 months postoperatively.One patient in the group treated with high ligation of the great saphenous vein combined with foam sclerotherapy suffered deep vein thrombosis of lower extremity after operation.In terms of quality of life,there was no statistically significant difference in venous clinical severity score(VCSS)among the three groups at 3 months postoperatively(P＞0.05).The group treated with simple foam sclerotherapy showed significantly shorter hospitalization days compared with the other two groups.Additionally,the group treated with simple foam sclerotherapy showed lower hospitalization expenses,which was not statistically significant when compared to the group treated with high ligation and stripping of the great saphenous vein group(P＞0.05),but there was a statistical difference compared to the group treated with high ligation of the great saphenous vein combined with foam sclerotherapy(P＜0.05).Conclusion There are no significant differences in clinical efficacy,postoperative pain,and quality of life evaluation among the three methods.However,simple foam scle-rotherapy may reduce the length of hospitalization stay and direct medical costs.

This article reported a case of generalized arterial calcification in infancy (GACI), which was suspected prenatally and confirmed postnatally. At 24 weeks of gestation, a systematic ultrasound revealed aortic wall thickening with hyperechogenicity, a thickened mitral valve accompanied by hyperechoic changes, thickened and calcified tricuspid valves, and multiple hyperechoic foci in both ventricles. A follow-up echocardiography at 28 weeks showed no significant progression. Emergency cesarean section was performed at 31 weeks due to fetal distress. Postnatal echocardiography confirmed generalized arterial calcification. Whole-exome trio sequencing identified two variants in the ENPP1 gene: c.1274-2A>G and c.1437+3(IVS14)_c.1437+6(IVS14)delGAGT. Based on imaging, laboratory results, and genetic testing, the infant was diagnosed with GACI type 1, concomitant with autosomal recessive hypophosphatemic rickets type 2. Given the poor prognosis, the family withdrew from further medical intervention.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective:To study the efficacy of low-intensity focused ultrasound (LIFU) on neuropathic pain (NP) in mice, and its effect on the activation of astrocytes and the expression of pro-inflammatory cytokines were discussed.Methods:Thirty-six male C57BL/6J mice were randomly divided into three groups: sham operation (Sham) group and chroinc constriction injury (CCI) model group and treatment (CCI+ LIFU) group, 12 mice in each group.NP model was established by CCI on the sciatic nerve. The group of CCI+ LIFU received LIFU treatment for the anterior cingulate cortex (ACC) on the 7th day after surgery, the mechanical withdrawal threshold (MWT) on the affected side of mice was measured at preoperation 3, 6, 12, 18, 24, and 27 days after operation, respectively, H&E staining was used to observe pathological morphological changes in the ACC region, the expression levels of ACC region AQP4 and GFAP protein were detected by Western Blot and immunofluorescence, and the expression levels of ACC region pro-inflammatory cytokines IL-1β and TNF-α were detected by enzyme-linked immunosorption assay.Results:Compared with Sham group, MWT in the CCI group decreased from the 3rd day until the 27th day after surgery( P<0.05); Compared with the CCI group, the MWT in the CCI+ LIFU group increased on the 24th day after surgery, and was significantly higher than that of the CCI group on the 24th and 27th day after surgery ( P<0.05); LIFU stimulation did not produce significant pathological changes in the ACC region; Western Blot and immunofluorescence showed that AQP4 and GFAP protein expression in the ACC region were upregulated ( P<0.05) after peripheral nerve injury, while AQP4 and GFAP protein expression was downregulated after LIFU treatment ( P<0.05); Enzyme-linked immunosorbents showed that the expression of pro-inflammatory cytokines IL-1β and TNF-α in the region of ACC was upregulated ( P<0.05) after peripheral nerve injury, while the expression of IL-1β and TNF-α was downregulated after LIFU treatment ( P<0.05). Conclusions:LIFU can effectively relieve mechanical pain sensitivity symptoms in mice induced by CCI, possibly by inhibiting activation of astrocytes and neuro-inflammatory responses.

Male infertility has evolved from a common reproductive system disease to a major social issue. Youjing granule (YG) is a Chinese medicinal material used as a therapy method for tonifying the kidneys and removing dampness due to its pathogenic characteristics. YG has been shown to regulate sperm quality in clinical trials, but the underlying mechanism is not fully understood. The present study was aimed to explore the protective effects and mechanism of action of YG on male reproductive system damage caused by methyl methane sulfonate (MMS). We first established an infertility model of rats through oral administration of MMS and then treated with YG. To determine the effect of YG, spermatogenesis, microvascular density, and secretory function of Leydig cells and Sertoli cells in rats were assessed. Spermatogonial stem cells (SSCs) were co-cultured with mouse embryo fibroblast (MEF) cells as an in vitro cell model before exposure to serum containing YG. Furthermore, the proliferation and apoptosis of SSCs were measured. Results indicated that YG increased the expression of self-renewal and proliferation-related molecules such as glial cell line derived neurotrophic factor (GDNF) and fibroblast growth factor-2 (FGF2), and improved the quality of sperm and the proliferation of SSCs. In conclusion, YG may protect spermatogenetic function of rats through regulating the proliferation and self-renewal of SSCs.
Animals ; Cell Proliferation ; Male ; Mice ; Rats ; Semen ; Spermatogenesis ; Spermatogonia ; Stem Cells

Puerarin was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) by periodate oxidation to serve as the immunogen and coating antigen, respectively. BALB/c mice were immunized with puerarin-BSA according to the routine immunization procedure, and the titer and specificity of serum were detected after three immunization. After booster immunization, mouse spleen lymphocytes were fused with mouse myeloma cells, and 24 hybridoma cell lines of the monoclonal antibodies against puerarin were screened by monoclonal antibody screening technique. Ascites was prepared and purified. The cross-reactivity of monoclonal antibody(mAb) M1 with 4'-methoxy puerarin, daidzin, puerarin-6″-O-xyloside, daidzein, mirificin, 3'-methoxy puerarin, and 3'-hydroxy puerarin was 239.84%, 112.18%, 67.89%, 58.28%, 22.37%, 0.40%, and 0.20%, respectively, and those with other analogs such as baicalein and baicalin were all less than 0.10%. The IC_(50) and the working range of the indirect competitive enzyme-linked immunosorbent assay(icELISA) for puerarin were 44.80 ng·mL~(-1) and 8.20-292.30 ng·mL~(-1), respectively. The average recovery was 91.95%-98.20% with an RSD in the range of 0.70%-2.60%. The content of puerarin in different Puerariae Lobatae Radix samples was determined with icELISA and validated by UPLC-MS. The correlation between data obtained from icELISA and UPLC-MS was 0.999 0, indicating that icELISA is suitable for the rapid detection of puerarin in Puerariae Lobatae Radix samples.
Animals ; Antibodies, Monoclonal ; Chromatography, Liquid ; Enzyme-Linked Immunosorbent Assay/methods* ; Hybridomas/metabolism* ; Isoflavones ; Mice ; Mice, Inbred BALB C ; Tandem Mass Spectrometry