OBJECTIVE: To explore the clinical application of transurethral steam thermal ablation of the prostate as an ultra-minimally invasive treatment of benign prostatic hyperplasia (BPH). METHODS: We treated 18 BPH patients by transurethral steam thermal ablation of the prostate in our hospital, and followed them up for 6－12 months after operation. We obtained the IPSS, maximum urinary flow rate (Qmax), IIEF-5 scores, Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form (MSHQ-EjD-SF) scores and quality of life (QOL) scores from the patients and compared them before and after surgery. RESULTS: Operations were successfully completed in all the cases, with no intraoperative complications, and all the patients were discharged on the second day after surgery. At the 6-month follow-up after surgery, the Qmax increased from (10.08 ± 2.06) ml/s before surgery to (7.51 ± 3.21) ml/s, the IPSS decreased from 23.72 ± 1.87 to 8.06 ± 1.39, and the QOL score decreased from 5.11 ± 0.58 before surgery to 1.28 ± 0.46. The differences in these indicators were statistically significant (P<0.05). And these is no significant difference in the MSHQ-EjD-SF and IIEF-5 score(P>0.05). CONCLUSION Transurethral steam thermal ablation of the prostate is a safe, effective and almost non-invasive surgical strategy for the treatment of BPH, with a good prospect of clinical application.
Humans ; Male ; Prostatic Hyperplasia/surgery* ; Aged ; Middle Aged ; Treatment Outcome ; Steam ; Transurethral Resection of Prostate/methods* ; Quality of Life

Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.

Caspase-2, a highly conserved member of the caspase family, is considered an initiator caspase that triggers apoptosis in response to some cellular stresses. Previous studies suggest that an intracellular multi-protein complex PIDDosome, induced by genotoxic stress, serves as a platform for caspase-2 activation. Due to caspase-2's inability to process effector caspases, however, the mechanism underlying caspase-2-mediated cell death upon PIDDosome activation remains unclear. Here, we conducted an unbiased genome-wide genetic screen and identified that the Bcl2 family protein BID is required for PIDDosome-induced, caspase-2-mediated apoptosis. PIDDosome-activated caspase-2 directly and functionally processes BID to signal the mitochondrial pathway for apoptosis induction. In addition, a designed chemical screen identified a compound, HUHS015, which specifically activates caspase-2-mediated apoptosis. HUHS015-stimulated apoptosis also requires BID but is independent of the PIDDosome. Through extensive structure-activity relationship efforts, we identified a derivative with a potency of ~60 nmol/L in activating caspase-2-mediated apoptosis. The HUHS015-series of compounds act as efficient agonists that directly target the interdomain linker in caspase-2, representing a new mode of initiator caspase activation. Human and mouse caspase-2 differ in two crucial residues in the linker, rendering a selectivity of the agonists for human caspase-2. The caspase-2 agonists are valuable tools to explore the physiological roles of caspase-2-mediated cell death and a base for developing small-molecule drugs for relevant diseases.
Caspase 2/genetics* ; Humans ; BH3 Interacting Domain Death Agonist Protein/metabolism* ; Apoptosis/drug effects* ; Death Domain Receptor Signaling Adaptor Proteins/metabolism* ; Animals ; Mice ; Cysteine Endopeptidases

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.
Animals ; Mice ; Rats ; Proto-Oncogene Proteins c-akt ; Network Pharmacology ; Alzheimer Disease/drug therapy* ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/genetics* ; Tandem Mass Spectrometry ; Drugs, Chinese Herbal/pharmacology*

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Pregnancy ; Female ; Humans ; Placenta ; Nuclear Transfer Techniques ; Embryo, Mammalian ; Cell Nucleus

OBJECTIVE: To investigate the surgical skills and clinical curative results of arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome. METHODS: From February 2019 to August 2020, 13 patients with ankle instability combined with anteromedial impingement were retrospectively analyzed. There were 10 males and 3 females with age of (40.0±15.1) years old. The course of disease was(44.1±33.2) months. All patients had history of ankle sprain. MRI showed the injury of anterior talofibular ligament. All patients had anteromedial pain and pressing pain when ankle dorsiflexion. All patients were treated with ankle debridement and Brostr?m-Gould surgery under ankle arthroscopic. Postoperative results were evaluated by VAS(visual analogue scale) and AOFAS-AH(American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale, AOFAS-AH). RESULTS: All 13 patients completed the surgery successfully with an operative time of 60 to 90 minutes. All the surgical incisions healed by first intention, and no complications such as incision infection, skin necrosis and neurovascular injury. Follow-up time was (18.1±4.7) months. At the latest follow-up, the VAS score was 1.2±1.1, which was significantly lower than the preoperative score 4.8±1.5 (P<0.05);the AOFAS-AH score 94.2±5.1 was significantly higher than the preoperative score 65.5±11.5 (P<0.05). The AOFAS-AH score at the final follow-up ranged from 84 to 100. All patients walked with normal gait without ankle instability or impingement recurrence. CONCLUSION Ankle anteromedial impingement syndrome combined with ankle instability is easy to be ignored clinically. Such kind of anteromedial impingement syndrome is mostly related to osteophyte at dorsal medial talar neck. Arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome has satisfactory curative effect with safety and minimal injury.
Adult ; Ankle ; Arthroscopy/methods* ; Female ; Humans ; Joint Instability/surgery* ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult