Objective:To investigate the therapeutic efficacy and disruptive effects of Meropenem（MEM）-loaded microbubbles（MBs）combined with ultrasound targeted microbubble destruction（UTMD）technology on Escherichia coli and its biofilm.Methods:MEM-MBs were prepared using the thin-film hydration method，and their characterization was assessed using a Zeta potential analyzer，with morphological observations conducted under an optical microscope. An in vitro biofilm model of periprosthetic joint infection（PJI）caused by Escherichia coli was constructed，and the morphology of the biofilm and the distribution of MEM-MBs in the bacterial biofilm were observed under a laser confocal microscope after staining the biofilm with SYTO59 staining and DIL staining for Microbubbles. The biofilm morphology and the distribution of MEM-MBs in bacterial biofilm were observed under laser confocal microscope. The biofilms were randomly divided into 5 groups using a random number table：control，Meropenem（MEM），MEM-MBs，UTMD，and MEM-MBs+UTMD，with 12 samples per group. After applying the respective interventions，scanning electron microscopy（SEM）and laser scanning confocal microscopy（LSCM）were employed to observe the effects on the morphology and structure of Escherichia coli and its biofilm. Crystal violet staining was utilized to determine and compare the biofilm density among groups using a microplate reader. LSCM was also used to observe the biofilm thickness，while both LSCM and spread plate counting were employed to assess bacterial viability differences across groups.Results:①MEM-MBs meeting the experimental requirements were successfully constructed.②A dense Escherichia coli biofilm visible under both the naked eye and LSCM was established，with a thickness of（10.61 ± 0.17）μm and a proportion of dead bacteria within the biofilm of（16.8 ± 0.8）%.③MEM-MBs were observed to penetrate into all layers of the biofilm using LSCM.④The results of crystal violet staining showed a decreasing trend in the biofilm density of the control group，the MEM group，the MEM-MBs group，the UTMD group，and the MEM-MBs+UTMD group. There was no significant difference between the MEM group and the MEM-MBs group（ P＞0.05），while there was a significant difference in biofilm density between the other groups，as revealed by pairwise comparison（all P＜0.05）.⑤UTMD technique and MEM-MBs+UTMD could significantly disrupt the biofilm of Escherichia coli. LSCM results showed that，compared to the control group，the thickness of the biofilm was reduced in all other groups，with only the UTMD group and the MEM-MBs+UTMD group showing an increase in porosity（both P＜0.05）. In comparison with the MEM group and the MEM-MBs group，the UTMD group showed an increase in porosity，while the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05）. Additionally，compared to the UTMD group，the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05），based on laser confocal microscopy results.⑥The results of the plate counting and LSCM showed that，compared with the control group，clump counts decreased，and the proportion of dead cells increased in the MEM group，the MEM-MBs group，and the MEM-MBs+UTMD group（all P＜0.05）. Compared with MEM group and MEM-MBs group，the clump counts of UTMD group increased，the proportion of dead cells decreased（all P＜0.05）；the clump counts of MEM-MBs+UTMD group decreased，and the proportion of dead cells increased（all P＜0.05）.Compared with UTMD group（all P＜0.05），the clump counts of MEM-MBs+UTMD group decreased，while the proportion of dead cells increased（all P＜0.05）.⑦The results of scanning electron microscopy revealed that the network structure of Escherichia coli was completely destroyed in the MEM-MBs+UTMD group. Conclusions:UTMD technology combined with MEM-MBs exerts a significant disruptive effect on the morphology and structure of Escherichia coli biofilm and significantly enhances bactericidal efficacy.

Objective:To investigate the therapeutic efficacy and disruptive effects of Meropenem（MEM）-loaded microbubbles（MBs）combined with ultrasound targeted microbubble destruction（UTMD）technology on Escherichia coli and its biofilm.Methods:MEM-MBs were prepared using the thin-film hydration method，and their characterization was assessed using a Zeta potential analyzer，with morphological observations conducted under an optical microscope. An in vitro biofilm model of periprosthetic joint infection（PJI）caused by Escherichia coli was constructed，and the morphology of the biofilm and the distribution of MEM-MBs in the bacterial biofilm were observed under a laser confocal microscope after staining the biofilm with SYTO59 staining and DIL staining for Microbubbles. The biofilm morphology and the distribution of MEM-MBs in bacterial biofilm were observed under laser confocal microscope. The biofilms were randomly divided into 5 groups using a random number table：control，Meropenem（MEM），MEM-MBs，UTMD，and MEM-MBs+UTMD，with 12 samples per group. After applying the respective interventions，scanning electron microscopy（SEM）and laser scanning confocal microscopy（LSCM）were employed to observe the effects on the morphology and structure of Escherichia coli and its biofilm. Crystal violet staining was utilized to determine and compare the biofilm density among groups using a microplate reader. LSCM was also used to observe the biofilm thickness，while both LSCM and spread plate counting were employed to assess bacterial viability differences across groups.Results:①MEM-MBs meeting the experimental requirements were successfully constructed.②A dense Escherichia coli biofilm visible under both the naked eye and LSCM was established，with a thickness of（10.61 ± 0.17）μm and a proportion of dead bacteria within the biofilm of（16.8 ± 0.8）%.③MEM-MBs were observed to penetrate into all layers of the biofilm using LSCM.④The results of crystal violet staining showed a decreasing trend in the biofilm density of the control group，the MEM group，the MEM-MBs group，the UTMD group，and the MEM-MBs+UTMD group. There was no significant difference between the MEM group and the MEM-MBs group（ P＞0.05），while there was a significant difference in biofilm density between the other groups，as revealed by pairwise comparison（all P＜0.05）.⑤UTMD technique and MEM-MBs+UTMD could significantly disrupt the biofilm of Escherichia coli. LSCM results showed that，compared to the control group，the thickness of the biofilm was reduced in all other groups，with only the UTMD group and the MEM-MBs+UTMD group showing an increase in porosity（both P＜0.05）. In comparison with the MEM group and the MEM-MBs group，the UTMD group showed an increase in porosity，while the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05）. Additionally，compared to the UTMD group，the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05），based on laser confocal microscopy results.⑥The results of the plate counting and LSCM showed that，compared with the control group，clump counts decreased，and the proportion of dead cells increased in the MEM group，the MEM-MBs group，and the MEM-MBs+UTMD group（all P＜0.05）. Compared with MEM group and MEM-MBs group，the clump counts of UTMD group increased，the proportion of dead cells decreased（all P＜0.05）；the clump counts of MEM-MBs+UTMD group decreased，and the proportion of dead cells increased（all P＜0.05）.Compared with UTMD group（all P＜0.05），the clump counts of MEM-MBs+UTMD group decreased，while the proportion of dead cells increased（all P＜0.05）.⑦The results of scanning electron microscopy revealed that the network structure of Escherichia coli was completely destroyed in the MEM-MBs+UTMD group. Conclusions:UTMD technology combined with MEM-MBs exerts a significant disruptive effect on the morphology and structure of Escherichia coli biofilm and significantly enhances bactericidal efficacy.

Objective To analyze the clinical efficacy of 450 nm blue laser vaporization in the treatment of benign prostatic hyperplasia(BPH)and to summarize the preliminary experience.Methods Clinical data of 30 BPH patients who underwent transurethral 450 nm blue laser vaporization at our hospital during Jun.and Sep.2023 were selected.The operation time,hemoglobin decrease value,bladder irrigation time,catheterization time,and incidence of complications were recorded.The changes in the international prostate symptom score(IPSS),quality of life score(QoL),postvoid residual(PVR)volume,and maximum urinary flow rate(Qmax)were compared before and 3 months after surgery.Results All operations were successfully completed without conversion to transurethral resection of the prostate(TURP)or open surgery.The operation time was(38.2±7.5)minutes,the hemoglobin decrease value was(10.4±3.5)g/L 24 hours after surgery,the bladder irrigation time was(15.1±3.3)hours,and the catheterization time was(4.5±0.5)days.Compared to preoperative,3 months after surgery,the IPSS[(26.28±2.22)vs.(6.29±2.10)],QoL[(5.25±0.85)vs.(2.33±0.95)],and PVR were decreased[(397.89±8.47)mL vs.(15.62±2.17)mL],while the Qmax was increased[(8.15±2.09)mL/s vs.(19.50±2.51)mL/s],with statistical significance(P＜0.05).Mild bladder mucosal injury occurred in 2 cases(6.6％)during surgery,a second indwelling catheter was placed in 1 case(3.3％)after surgery,and gross hematuria occurred in 1 case(3.3％)after surgery.No serious complications occurred.Conclusion The use of 450 nm blue laser vaporization for the treatment of BPH has advantages of fast,efficient and reliable hemostasis,and low incidence of complications,which can effectively improve urination and is worthy of clinical promotion and application.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development.

Objective To explore the role of deep brain stimulation of subthalamic nucleus (STN-DBS) in treatment of Parkinson's disease (PD) related neuroleptic malignant syndrome (NMS).Methods The medical history,clinical features,STN-DBS programmed treatment process and treatment results of two patients admitted to our hospital in December 2014 and November 2018 were retrospectively analyzed.Results Two patients with post-operative STN-DBS were evoked by dose-reduced treatment of anti-parkinsonian drugs,and presented with high fever,disorder of consciousness,aggravation of the original parkinsonism,and increase of creatine phosphokinase,which were not correlated with outcomes of infection.After admission,anti-parkinsonian drugs and other supportive therapies were supplemented;STN-DBS modulation were given to improve the symptoms;the final parameters of patient one were the left (C+,2-,1-),pulse width 110 μs,frequency 200 Hz,and strength 3.8 V;the right side (C+,6-,5-),pulse width 110 μs,frequency 200 Hz,strength 4.4 V;and those of patient two were the left (C+,3-),pulse width 60 μs,frequency 130 Hz,strength 2.0 V;right side (C+,6-),pulse width 80 μs,frequency 160 Hz,and strength 2.8 V.Both patients were cured,but their motor function and self-care ability were severely impaired.Conclusion STN-DBS may play an important role in the treatment of PD related NMS.

Objective To evaluate the effects of a single preoperative dose of gabapentin on buprenorphine patient controlled intravenous analgesia after modified radical mastectorny. Methods Sixty female patients,ASA physical starus Ⅰ and Ⅱ undergoing modified radical mastectomy under general anesthesia were divided into two groups of 30 each group by random digits table to receive either gabapentin 1200 mg (gabapentin group) or a matching placebo (control group), administered orally 2 h before the induction of anesthesia. Subjects received patient controlled intravenous buprenorphi(n)e analgesia during thepostoperative period. Fifty-three patients finished this study, 28 cases in control group,25 cases in gabapentin group. Postoperative pain (static and dynamic),postoperative nausea and vomiting,anxiety,sedation were assessed by pain visual analogue scale(VAS), four-point ordinal scale, anxiety visual analogue scale, Ramsay sedation scale respectively. Postoperative buprenorphine consumption and time to first patient controlled analgesia were observed. Results Postoperative VAS (static and dynamic) was lower in gabapentin group than that in control group (P ＜0.05). Postoperative buprenorphine consumption was (506.1 ±37.9)μg , time to first patient controlled analgesia was (21.1 ±2.3)min,incidence rate of postoperative nausea and vomiting was 40.0% (10/25), antemetic rate was 12.0% (3/25), grade of anxiety was (28.5 ± 12.1) scores in gabapentin group, (699.8 ± 87.8)μ g, (4.3 ±0.8) min,64.3% (18/28),32.1%(9/28) and (66.3±15.7) scores in control group respectively. There were significant differences between two groups (P ＜ 0.05). Conclusion A single preoperative oral dose of gabapentin 1200 mg can effectively attenuate postoperative pain,reduce the consumption of buprenorphine,decrease the incidence rate of postoperative nausea and vomiting,improve patients' anxiety in patients undergoing modified radical mastectomy under general anesthesia.

AIM: To observe the effects of Egr-1 gene knockout on the expression of inflammatory-related factors in pancreatic tissue in a mouse acute pancreatitis model.METHODS: The experimental pancreatitis was induced by high-dose of cearulein in wildtype mice and Egr-1 knockout mice.The pancreatitis indexes,such as serum amylase,pancreata edema,and myeloperoxidase(MPO) levels in pancreata and lungs were recorded.The mRNA levels of tissue factor(TF),plasminogen activator inhibitor(PAI-1),monocyte chemoattractant protein(MCP-1),Gro-1,IL-6 and ICAM-1 were measured by quantitative PCR.RESULTS: Contrary to wildtype mice,typical pancreatitis was not induced by high-dose cearulein in the Egr-1 knockout mice,not only markedly reduced edema in pancreata and lungs,but decreased MPO levels in lungs as well were found.Furthermore,the mRNA of TF,PAI,MCAP,ICAM-1 and IL-6 in pancreata were significantly decreased in Egr-1 knockout mice.CONCLUSION: The severity of pancreatitis and lung damage is ameliorated in Egr-1 knockout mice stimulated by high-dosage of cearulein,which was probably mediated by decreasing expression of inflammatory-related factors in pancreata,such as TF,PAI,MCP-1,ICAM-1 and IL-6.