Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

OBJECTIVE: To explore the role of antibiotic-eluting absorbable calcium sulfate in treating periprosthetic infection after one-stage revision of knee arthroplasty. METHODS: A retrospective analysis was performed on 36 patients(36 knees)who underwent phaseⅠrevision for periprosthesis infection after total knee arthroplasty from January 2018 to March 2022. All patients were underwent knee cavity puncture before operation and had positive results of aseptic body fluid culture, 21 patients received revision combined with antibiotic loaded calcium sulfate at stageⅠ(calcium sulfate group) during operation, and 15 patients underwent renovation at stageⅠ(revision group). There were 9 males and 12 females in calcium sulfate group, aged from 54 to 76 years old with an average of(67.6±6.2) years old. There were 15 patients in revision group, including 4 males and 11 females, aged from 60 to 75 years old with average of (69.6±4.1) years old. The levels of serum C-reactive protein (CRP), interleukin-6 (IL-6) at 7, 14, 30 and 90 days after operation were compared between two groups, and the rate of end-infection control at follow-up were compared. The systemic antibiotic application time, hospital stay and postoperative complications were observed between two groups. RESULTS: Calcium sulfate group were followed up for 12 to 29 months with an average of(18.9±4.2) months, and the infection control rate was 90.5%;while revision group were followed up 18 to 29 months with average of (21.6±3.7) months, and the infection control rate was 86.7% (13/15). There were no significant differences in follow-up time and infection control rate between two groups(P>0.05). Postoperative levels of CRP and IL-6 at 7, 14 and 30 days in calcium sulfate group were (32.79±11.48), (15.50±6.52), (9.36±3.32) mg·L^-1 and (17.31±6.15) pg·ml^-1, respectively;which were lower than those in revision group (40.65±11.32), (30.15±10.57), (18.97±5.86) mg·L^-1 and (25.54±6.73) pg·ml^-1, had statistical differences(P<0.05). There were no significant differences in IL-6 levels at 7 and 14 days after operation and CRP levels at 90 days after operation between two groups (P>0.05). The hospitalization time and systemic antibiotic application time in calcium sulfate group were (18.4±2.2) and (63.5±21.4) d, respectively;which were better than those in revision group (20.5±2.4) and (82.7±16.9) d, and had statistical differences(P<0.05). No significant wound complications and hypercalcemia were observed in calcium sulfate group. CONCLUSION Antibiotic eluted absorbable calcium sulfate could be used to treat periprosthetic knee infection, significantly reducing CRP levels in the early postoperative period, shortening hospital stay and systemic antibiotic application time, but it does not significantly improve the control rate of revision infection at stageⅠ.
Humans ; Male ; Female ; Aged ; Prosthesis-Related Infections/surgery* ; Middle Aged ; Calcium Sulfate/administration & dosage* ; Arthroplasty, Replacement, Knee/adverse effects* ; Retrospective Studies ; Anti-Bacterial Agents/therapeutic use* ; Interleukin-6/blood* ; C-Reactive Protein/metabolism* ; Reoperation ; Knee Prosthesis/adverse effects*

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Thromboembolic disease seriously affects people's health, and even endangers life. Nattokinase(NK) is an alkaline serine protease with strong thrombolytic activity and low toxicity. However, when NK passes through the stomach, it is degraded by gastric acid and pepsin, and subsequently loses its thrombolytic activity. The application of preparation technology can form a protective layer and improve the high bioavailability of NK. This article briefly introduced the pharmacological properties of NK, and discussed the characteristic of different dosage forms. The development of NK preparation was prospected in order to promote its research and application.

Objective To explore the clinical effect of timolol maleate combined with cryotherapy for infantile cutaneous hemangioma.Methods A total of 240 infants with cutaneous hemangioma were randomly divided into the control group(120 cases)and the combined group(120 cases).The control group was treated with timolol maleate,and the combined group was treated with timolol maleate combined with cryotherapy.The clinical efficacy,tumor diameter,levels of serum matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)and the occurrence of adverse reactions of the two groups were compared.Results The total effective rate of the combined group was significantly higher than that of the control group(P<0.05).Compared with before treatment,the tumor diameter 3 months and 6 months after treatment in the two groups gradually decreased(P<0.05),and the tumor diameter 3 months and 6 months after treatment in the combined group decreased more obviously(P<0.05).Compared with before treatment,the levels of serum MMP-9 and VEGF 3 months and 6 months after treatment in the two groups gradually decreased(P<0.05),and the levels of serum MMP-9 and VEGF 3 months and 6 months after treatment in the combined group were significantly lower than those in the control group(P<0.05).There was no statistically significant difference in the total incidence of adverse reactions such as eczema,ulcer,erosion or redness between the two groups(P>0.05).Conclusion Timolol maleate combined with cryotherapy for infantile cutaneous hemangioma has significant curative effect,which can effectively reduce the levels of serum MMP-9 and VEGF,and shrink the tumor body,with safety and effectiveness.

Objective:To conduct a comparative analysis of the radiation damage to zebrafish embryos and the associated biological mechanism after ultra-high dose rate (FLASH) and conventional dose rate irradiation.Methods:Zebrafish embryos at 4 h post-fertilization were exposed to conventional and FLASH irradiation (9 MeV electron beam). The mortality and hatchability of zebrafish after radiation exposure were recorded. Larvae at 96 h post-irradiation underwent morphological scoring, testing of reactive oxygen species (ROS) levels, and analysis of changes in oxidative stress indicators.Results:Electron beam irradiation at doses of 2-12 Gy exerted subtle effects on the mortality and hatchability of zebrafish embryos. However, single high-dose irradiation (≥ 6 Gy) could lead to developmental malformation of larvae, with conventional irradiation showing the most significant effects ( t = 0.87-9.75, P < 0.05). In contrast, after FLASH irradiation (≥ 6 Gy), the ROS levels in zebrafish and its oxidative stress indicators including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were significantly reduced ( t = 0.42-15.19, P < 0.05). There was no statistically significant difference in ROS levels in incubating solutions after conventional and FLASH irradiation ( P > 0.05). Conclusions:Compared to conventional irradiation, FLASH irradiation can reduce radiation damage to zebrafish embryos, and this is in a dose-dependent manner. The two irradiation modes lead to different oxidative stress levels in zebrafish, which might be a significant factor in the reduction of radiation damage with FLASH irradiation.

Objective To report a case of synovial sarcoma of the liver and review the literature for improving the understanding of the disease.Methods The clinical data of a patient with liver synovial sarcoma admitted to the First Affiliated Hospital of Henan University were analyzed retrospectively.The imaging,pathological features,treatment and prognosis of this disease were summarized by searching the database(CNKI,Wanfang Data,PubMed,untill July 2022)and the literature results analyzed comprehensively.Results The patient was a 71-year-old female who was admitted to the hospital due to abdominal pain.Computed tomography(CT)scan showed a mass with mixed density in the right lobe and caudate lobe of the liver.The large cross section size was about 115 mm×87 mm and the mass showed continuous heterogeneous enhancement,being considered as malignant hepatic tumors with multiple metastasis of the liver and lung.Ultrasound-guided needle biopsy was performed,and microscopy showed the tumor cells were obvious atypical,and some were spindle-shaped.Immunohistochemistry showed that the patient was positive for vimentin(VIM),epithelial membrane antigen(EMA),methylation of histone at lysine 27(H3K27Me3),and negative for pan cytokeratin(CK-pan)and S-100,and pathological diagnosis of synovial sarcoma was made.The patient did not undergo subsequent treatment and was lost to follow-up after discharge.A total of 12 cases of hepatic synovial sarcoma were reported after searching the database.The clinical manifestations were abdominal pain or distention.The lesions were mostly located in the right lobe of the liver,usually large,heterogeneous density,and heterogeneous enhancement on enhanced CT or magnetic resonance imaging(MRI).Spindle-shaped cells were found at histopathologic examination.Immunohistochemistry showed the patient was positive for VIM,EMA,H3K27Me,B-cell leukemia/lymphoma-2(BCL-2)and transducer-like enhancer of split 1(TLE1).SS18-SSX fusion gene or SS18 gene isolation were detected.Eleven patients received surgical treatment,5 received adjuvant chemotherapy,and 4 had recurrence or metastasis during the follow-up period.Conclusions Synovial sarcoma of the liver is a rare malignant tumor of the liver.The clinical and imaging features are not specific.The diagnosis depends on pathology.At present,the main treatment is surgery,and comprehensive treatment such as adjuvant chemotherapy can be performed.The prognosis of the patient is poor.

Objective To explore the role of pulmonary surfactant(PS)combined with budesonide in improving oxygenation and clinical outcomes of neonatal acute respiratory distress syndrome(ARDS).Methods The present study is a historically controlled trial.Infants with ARDS requiring mechanical ventilation and PS replacement therapy were collected from the neonatal unit of Southwest Medical University.Those from January 2022 to November 2022 were set as intervention group(PS+ budesonid,n=35),treated with intratracheal instillation of a mixed suspension of budesonide(0.25 mg/kg)and PS(200 mg/kg),and continuous budesonide nebulization(0.25 mg/kg,twice per day)until withdrawal,then compared with a historical cohort,who just received intratracheal instillation of PS(200 mg/kg)(January 2020-December 2021,PS group,n=35).Baseline data such as gender,mode of delivery,1 min and 5 min Apgar score,birth weight,gestational age,time of onset,and cause of onset were recorded in both groups.The oxygenation and clinical outcomes of infants were compared between the two groups,including:(1)Arterial blood gas analysis indicators,such as partial pressure of oxygen(PaO2)and oxygenation index(OI)before treatment and at 6,12 and 24 hours of treatment;(2)Clinical observation and evaluation indicators,such as the time to withdrawal,duration of oxygen supplementation,length of stay,improvement of the radiological images of the lungs at 72 h of treatment,and repeated PS use;(3)Blood chemistry indicators,such as white blood cell(WBC),neutrocyte(NEU),procalcitonin(PCT)before treatment and at 3 and 7 days of treatment;and(4)Observation indicators of complications,weight growth,and mortality outcomes,such as the incidences of intracranial hemorrhage,gastrointestinal hemorrhage,neonatal necrotizing enterocolitis(NEC),and hyperglycemia,weight growth,and fatality rate.Results The differences in baseline data between the two groups were not statistically different(P＞0.05).The levels of PaO2 of the two groups were increased after treatment for different time periods,while the levels of OI were decreased(P＜0.001),and the levels of above indexes changed more significantly in PS+budesonide group than those in PS group(P＜0.05).The time to withdrawal,duration of oxygen supplementation,and length of stay in PS+budesonide group were shorter than those in PS group;the radiological images of the lungs showed that the pulmonary inflammation absorption was significantly better in PS+ budesonide group than that in PS group,while no significant difference between the two groups of infants with repeated PS use.The NEU was significantly higher in PS+budesonide group than in PS group at 3 d and 7 d of treatment(P＜0.001);and at 3 days of treatment,the PCT levels were significantly lower in PS+budesonide group than that in PS group(P＜0.05).The incidences of intracranial hemorrhage,gastrointestinal hemorrhage,NEC,hyperglycemia,weight growth,and fatality rate were not significantly different between the two groups(P＞0.05).Conclusion The use of budesonide in addition to surfactant may improve the oxygenation of neonates with ARDS,improve the inflammatory infiltrates in lungs,shorten the duration of mechanical ventilation and oxygen supplementation,and without short-term complications associated with budesonide use.