ObjectiveTo observe the clinical efficacy of Tangshen Dihuang decoction in treating diabetic kidney disease （DKD） with liver-kidney Yin deficiency and blood stasis syndrome and its impact on gut microbiota. MethodsA randomized controlled clinical trial was conducted， in which 102 DKD patients with liver-kidney Yin deficiency and blood stasis syndrome were randomly assigned to the Tangshen Dihuang decoction group and the control group. Each group consisted of 51 cases， and the treatment period was 3 months. The primary efficacy indicators included urinary albumin-to-creatinine ratio （UACR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （2 hPBG）， glycated hemoglobin （HbA₁C）， serum creatinine （SCr）， blood urea nitrogen （BUN）， angiotensinⅡ （AngⅡ）， serum cystatin C （Cys-C）， urinary N-acetyl-β-D-glucosaminidase （NAG）， urinary β₂-microglobulin （Uβ₂-MB）， traditional Chinese medicine （TCM） symptom scores， and gut microbiota. ResultsAfter treatment， the total response rate in the Tangshen Dihuang decoction was 87.23% （41/47）， which was higher than that （69.57%， 32/46） in the control group （Z=4.30， P<0.05）. After treatment， the TCM symptom scores decreased in both groups （P<0.01） and were lower in the Tangshen Dihuang decoction group than in the control group （P<0.01）. After treatment， the control group showed decreases in UACR， Uβ₂-MG， AngⅡ， and FBG （P<0.05） as well as 2 hPBG and HbA₁C （P<0.01）， and no significant differences in BUN， Cys-C， eGFR， SCr， and NAG. The Tangshen Dihuang decoction group showed increased eGFR （P<0.05）， declined levels of UACR， BUN， Cys-C， Uβ₂-MB， AngⅡ， FBG， 2 hPBG， NAG， and HbA₁C （P<0.01）， and no significant difference in SCr. The Tangshen Dihuang decoction group had lower BUN （P<0.05）， Cys-C （P<0.05）， AngⅡ （P<0.05）， 2 hPBG （P<0.05）， Uβ₂-MG （P<0.01）， and NAG （P<0.01） and higher eGFR level （P<0.05） than the control group. After treatment， the control group showed declines in Shannon， Observed_species， and Chao1 indices （P<0.05）. The samples from both groups showed statistically significant differences in the principal coordinates analysis （PCoA） plot based on Anosim analysis （P<0.05）. After treatment， the Tangshen Dihuang decoction group showed decreased relative abundance of Actinobacteria （P<0.05）. Moreover， the relative abundance of Actinobacteria was significantly lower in the Tangshen Dihuang decoction group than in the control group （P<0.05）. At the genus level， the control group showed decreased relative abundance of Bifidobacterium （P<0.05）， and the Tangshen Dihuang decoction group presented increased relative abundance of Bifidobacterium and Blautia_A （P<0.05）. After treatment， the Tangshen Dihuang decoction group had higher relative abundance of Bifidobacterium than the control group （P<0.01）. ConclusionTangshen Dihuang decoction has a significant therapeutic effect on DKD patients with liver-kidney Yin deficiency and blood stasis syndrome. It can markedly relieve clinical symptoms and reduce proteinuria and postprandial blood glucose by antagonizing the local renin-angiotensin system （RAS） and alleviating gut microbiota dysbiosis.

Jansen-de Vries syndrome, also known as intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, is a rare autosomal dominant disorder characterized by multisystem involvement. This article reports the case of a young child who presented with global developmental delay, gastrointestinal dysfunction, intellectual disability, and short stature. Distinct facial features included a broad forehead, low nasal bridge, thin upper lip, and widely spaced and misaligned teeth. Additional phenotypic findings involved small hands and feet, as well as digital anomalies. Through whole-exome sequencing (WES) and copy number variation (CNV) analysis, a pathogenic variant was identified in the PPM1D gene: c.1281G > A (p.Trp427Ter). This report also reviews the current literature on the clinical characteristics, diagnostic approaches, and therapeutic advances related to this condition, aiming to provide valuable insights for its clinical diagnosis and management.

OBJECTIVE: To compare the clinical efficacy of electroacupuncture (EA) at neuro-arterial stimulation points with topical western medication in treating post-stroke shoulder-hand syndrome (SHS). METHODS: A total of 72 patients with post-stroke SHS were randomly assigned to an observation group (n=36, 2 cases dropped out) and a control group (n=36, 3 cases dropped out). Both groups received standard neurological treatment, comprehensive rehabilitation, and physical therapy. The observation group received EA at neuro-arterial stimulation points, including the ipsilateral stellate ganglion point, vagus nerve trunk and auricular branch (left side), and stimulation points of the radial and ulnar arteries, radial nerve, ulnar nerve, and median nerve, once daily for 4 weeks. The control group was treated with topical diclofenac diethylamine emulgel, and mucopolysaccharide polysulfate cream was added for patients with pronounced early-stage edema, twice a day for 4 weeks. The VAS pain score and hand edema volume were recorded before treatment, at 2 and 4 weeks during treatment, and 2 weeks after treatment completion (follow-up). Musculoskeletal ultrasound was used to measure the thickness of the dorsal hand and middle finger skin on the affected side before and after 4 weeks of treatment. RESULTS: Compared before treatment, the VAS pain scores and edema volume of the affected hand in both groups were decreased at week 2, week 4, and follow-up (P<0.05). At week 4, both groups showed lower VAS pain scores and edema volume than those at week 2 (P<0.05); during follow-up, both VAS pain scores and edema volume were further reduced compared to those at week 4 (P<0.05). At week 2, week 4, and follow-up, the VAS scores and edema volume of the affected hand in the observation group were lower than those in the control group (P<0.05). Compared before treatment, the dorsal hand skin thickness and middle finger skin thickness on the affected side were decreased in both groups after 4 weeks of treatment (P<0.05). Compared with the control group, the observation group showed thinner dorsal hand and middle finger skin thickness after 4 weeks of treatment (P<0.05). CONCLUSION EA at neuro-arterial stimulation points effectively alleviates pain and edema in patients with post-stroke SHS, and demonstrates superior efficacy compared to topical western medication.
Humans ; Male ; Female ; Middle Aged ; Electroacupuncture ; Aged ; Stroke/complications* ; Acupuncture Points ; Adult ; Reflex Sympathetic Dystrophy/physiopathology* ; Treatment Outcome ; Hand

BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

Esculetin, a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini, has demonstrated significant pharmacological activities, including anticancer properties. Ferroptosis, an iron-dependent form of regulated cell death, has garnered considerable attention due to its lethal effect on tumor cells. However, the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma (HCC) effects remains poorly understood. This study investigated the impact of esculetin on HCC cells both in vitro and in vivo. The findings indicate that esculetin effectively inhibited the growth of HCC cells. Importantly, esculetin promoted the accumulation of intracellular Fe²⁺, leading to an increase in ROS production through the Fenton reaction. This event subsequently induced lipid peroxidation (LPO) and triggered ferroptosis within the HCC cells. The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde (MDA) levels, the depletion of glutathione peroxidase (GSH-Px) activity, and the disruption of mitochondrial morphology. Notably, the inhibitor of ferroptosis, ferrostatin-1 (Fer-1), attenuated the anti-tumor effect of esculetin in HCC cells. Furthermore, the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells. Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4, consequently alleviating esculetin-induced ferroptosis. In conclusion, this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis, thereby triggering ferroptosis in HCC cells. These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.
Umbelliferones/administration & dosage* ; Ferroptosis/drug effects* ; Carcinoma, Hepatocellular/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Humans ; Liver Neoplasms/physiopathology* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Animals ; Cell Line, Tumor ; Mice ; Amino Acid Transport System y+/genetics* ; Mice, Inbred BALB C ; Male ; Signal Transduction/drug effects* ; Lipid Peroxidation/drug effects* ; Reactive Oxygen Species/metabolism* ; Mice, Nude

Intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has become the primary treatment for macular edema associated with retinal vascular disease such as diabetic retinopathy and retinal vein occlusion, but there are limitations such as variable treatment efficacy and insufficient durability of therapeutic effects. As the first bispecific antibody applied in ophthalmic treatment, Faricimab achieves favorable outcomes by simultaneously targeting both VEGF-A and angiopoietin-2(Ang-2)pathways. Based on evidence from recent clinical trials and real-world studies, this article reviews the research progress on Faricimab for the treatment of diabetic macular edema(DME), retinal vein occlusion-associated macular edema(RVO-ME)and refractory macular edema compared to the therapeutic effects of other agents. Additionally, based on Faricimab's safety characteristics and future potential, its therapeutic prospects for macular edema associated with retinal vascular diseases are discussed. This review aims to provide evidence-based references for optimizing clinical treatment strategies, thereby contributing to mitigating the risk of vision loss due to macular edema.

•A strategy for in situ metabolically synthesized active drug-based probes was proposed.•The potential purgative targets of SA were successfully hooked and identified.•The work provided a new insight for studying the direct targets of unstable active drugs.

Objective To investigate the effects and mechamism of AdipoRon on oxidative stress and autophagy in diabetic kidney tissue in diabetes mellitas(DM)mice.Methods 24 male C57BL/6 mice were divided into normal control group(NC),DM group,AdipoRon group and AdipoRon combined with 3-MA(AdipoRon+3-MA)group,each group had 6 mice.Body weight,kidney index(KW/W),FPG,FIns,serum creatinine(Scr),BUN and APN levels were measured.Renal histomorphology was evaluated by HE staining.RT-PCR was used to detect the mRNA expression of p22phox,Nrf2,NQO-1,SOD,HO-1,LC3,PINK1,Parkin.Results Compared with NC group,KW/W,FPG,BUN,Scr and the mRNA expressions of p22phox in DM group were increased(P＜0.05),while weight,FIns,APN and the mRNA expressions of Nrf2,NQO-1,SOD,HO-1,LC3,PINK1 and Parkin were decreased in DM group(P＜0.05).Compared with DM group,FIns,APN,the mRNA expressions of Nrf2,NQO-1,HO-1,SOD,LC3,PINK1 and Parkin were increased(P＜0.05),while body weight,KW/W,FPG,BUN,Scr and p22phox were decreased in AdipoRon group(P＜0.05).After 3-MA intervention,the above results were reversed.Conclusions AdipoRon can protect the kidney injury in DM mice by reducing oxidative stress and increasing the level of autophagy.Oxidative stress and autophagy are involved in the process of diabetic kidney injury.

In this study,the carboxylated magnetic beads were coupled with bivalent nanobodies a-gainst porcine epidemic diarrhea virus(PEDV)M protein to construct immunomagnetic beads(IM-NBs-Ⅱ),The capture and enrichment function of IMNBs-Ⅱ was verified by using PEDV propaga-ted in Vero cells.A one-step RT-qPCR detection method for PEDV was established by combining the characteristics of IMNBs-Ⅱ with the detection advantages of reverse transcription fluorescence quantitative polymerase chain reaction(RT-qPCR).Specific analysis found that this method has no cross reactivity with swine fever virus,porcine reproductive and respiratory syndrome virus,por-cine parvovirus,porcine circovirus,indicating that it has good specificity.Sensitivity analysis re-vealed that the detection sensitivity of the RT-qPCR based on IMNBs-Ⅱ was increased 10 times compared to traditional RT-qPCR methods.Detection of the clinical samples confirm that the RT qPCR method based on IMNBs-Ⅱ is suitable for rapid and accurate detection of clinical feces and tissue samples.The method established in this study effectively avoids contamination issues during nucleic acid extraction,simplifies experimental procedures,and saves detection time,which pro-vides a method for efficient detection of PEDV.

Objective To clone the glycosyltransferase gene UGT708Z1 in Anemarrhena asphodeloides and perform its bioinformatics analysis,prokaryotic expression analysis and functional characterization.Methods A candidate glycosyltransferase gene UGT708Z1 was mined and screened out from Anemarrhena asphodeloides based on the transcriptome data.According to its full-length open reading frame,the specific primers with homologous arms were designed.Subsequently,the UGT708Z1 gene was cloned by PCR.The prokaryotic expression recombinant vector pET-32a(+)-UGT708Z1 was constructed through homologous recombination technology,and the soluble target protein was obtained by prokaryotic expression and purified protein technology.Finally,the function of UGT708Z1 was identified through enzymatic reaction in vitro.Results Sequence analysis showed that the open reading frame of UGT708Z1 was 1377 bp,encoding 458 amino acids.The result of prokaryotic expression showed that UGT708Z1 successfully expressed the soluble target protein,and the purified recombinant protein was 70.86 kDa.The results of enzymatic reaction in vitro showed that UGT708Z1 had flavonoid 7-OH glycosylation activity and could catalyze icaritin to produce icariside I.In addition,UGT708Z1 also possessed the activities of catalyzing the 7-O-glycosylation of quercetin and apigenin.Conclusion In this study,a flavonol glycosyltransferase UGT708Z1 was successfully cloned and identified from Anemarrhena asphodeloides,which would lay a foundation for further analysis of flavonol glycosides biosynthesis.