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.

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.

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*

•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.

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

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

BACKGROUND:The treatment of post-stroke dysphagia with Lipopharyngeal Qibi Formula has achieved good efficacy,and 5-hydroxytryptamine in peripheral serum and neurotransmitters in the nucleus tractus solitarius are closely related to swallowing.Therefore,this study was conducted to explore the modulatory effects of peripheral serum and nucleus tractus solitarius neurotransmitters in swallowing by using modern medical experimental methods such as molecular biology,thereby developing new ideas for the exploration of their mechanisms. OBJECTIVE:To verify the therapeutic effect of Lipopharyngeal Qibi Formula on post-stroke dysphagia and to investigate its mechanism of action. METHODS:Thirty-eight Sprague-Dawley rats were randomly divided into model group(n=14),treatment group(n=14)and sham-operated group(n=10).Animals in the model and treatment groups were modeled by reperfusion after 90 minutes of transient cerebral ischemia by wire bolus method.At 6 hours after modeling,neurological function was scored,and rats with a score of 2 were selected for subsequent experiments.The treatment group was given compound Lipopharyngeal Qibi Formula by gavage starting from the 2nd day after modeling and the remaining two groups were given normal saline by gavage.Changes in body mass,24-hour food and water intake were recorded on days 2,7,14 and 30.The swallowing initiation response time and the number of swallows were detected using a biosignal collector and a tonic transducer on days 14 and 30.After the swallowing test,the ischemic area of the brain in each group was measured by TTC staining.The expression of 5-hydroxytryptamine in the nucleus tractus solitarius of the medulla oblongata was measured by immunohistochemistry.The mRNA and protein expression levels of BCL-2 and BAX in the insula,premotor cortex,cingulate cortex and thalamus of rats in each group were measured by RT-PCR and Western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham-operated group,the body mass,24-hour food intake and water intake were reduced,the swallow initiation response time was prolonged,and the number of swallows was reduced in the treatment and model groups at day 14 of gavage(P＜0.05).Compared with the model group,the body mass,24-hour food intake and water intake of rats were increased in the treatment group at day 30 of gavage(P＜0.05),but were still lower than those in the sham-operated group.Compared with the model group,the swallow initiation reaction time was shortened and the number of swallows increased in the treatment group,but the number of swallows was still significantly lower than that in the sham-operated group(P＜0.05).Cerebral ischemia area was reduced in the treatment group compared with the model group,and the number of 5-hydroxytryptamine-positive cells in the nucleus tractus solitarius of the medulla oblongata was increased in the treatment group compared with the model group,but it was still significantly lower than that in the sham-operated group(P＜0.05).Compared with the model group,the expression of BCL-2 mRNA and protein in the insula,cingulate cortex and thalamus of rats in the treatment group were significantly increased,the expression of BAX mRNA and protein were significantly decreased,and the BCL-2/BAX ratio was significantly increased(P＜0.05).To conclude,the Chinese herbal compound Lipopharyngeal Qibi Formula could improve the number of swallows and swallowing initiation response time,as well as 24-hour food intake,body mass and other swallowing-related indexes in rats with post-stroke dysphagia.The mechanism of action may be achieved by improving the area of cerebral ischemia,inhibiting the apoptosis of neuronal cells in the insula,cingulate cortex and thalamus of rats,thus improving the regulation of the higher centers on the medulla oblongata swallowing center,and regulating the level of 5-hydroxytryptamine in the nucleus tractus solitarius.

Amid ongoing reforms in the healthcare system and the pursuit of high-quality development in public hospi-tals,the significance of party building in leading the standardization of hospital party branches has become increasingly promi-nent.Taking a university's affiliated hospital as an example,this study comprehensively analyzes the current situation of Party building on the standardized construction of party branches within university-affiliated public hospitals using the SWOT method.Meanwhile,this paper proposes targeted strategies by assessing the strengths,weaknesses,opportunities,and challenges of party building leadership.These strategies are intended to refine the framework for the role of Party building in advancing the standard-ized construction of Party branches in university-affiliated public hospitals.