Objective:To explore the expression of transmembrane protein 9(TMEM9)as an oncogene in prostate cancer(PCa),and to examine its effect on the proliferation and invasion of PCa cells as well as on the Wnt/β-catenin signaling pathway and autophagy of PCa cells by intervening with its expression.Methods:The Cancer Genome Atlas was used for pan-cancer analysis of TMEM9 expres-sion levels in different tumors,and TMEM9 protein and messenger ribonucleic acid(mRNA)levels in clinical PCa and prostatic hyper-plasia specimens were analyzed.Real-time quantitative polymerase chain reaction and western blotting were used to analyze TMEM9 expression levels in different PCa cell lines.Cell counting,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL),and Transwell assay were used to analyze cell proliferation,apoptosis,and PCa cell invasion,respectively.Subcutaneous tu-morigenesis in nude mice was used to analyze tumor proliferation in vivo.Western blotting was used to analyze the expression of autophagy-related pathway proteins,and transmission electron microscopy and immunofluorescence colocalization were used to deter-mine the colocalization of autophagosomes and lysosomes.Results:TMEM9 was highly expressed in PCa.The mRNA and protein ex-pression levels of TMEM9 were higher in PCa tissues than in prostatic hyperplasia tissues.The expression of TMEM9 was highest in PC3 cells(human PCa cells)(t=17.150,P<0.01).In TMEM9-knocked down PC3 cells,the proliferation(t=3.165,P<0.05)and inva-sion(F=76.620,P<0.01)significantly decreased,and apoptosis(t=13.530,P=0.010)significantly increased.After knockdown of TMEM9,the volume(F=1 699.000,P<0.01)and weight(t=9.057,P<0.01)of subcutaneous tumors in nude mice were reduced,and tu-mor growth was inhibited.TMEM9 regulated the Wnt/β-catenin signaling pathway and inhibited the AKT-mTOR signaling pathway to promote autophagy in PCa cells.Conclusion:TMEM9 inhibits the AKT-mTOR signaling pathway and promotes the proliferation and invasion of PCa cells through autophagy.

Porcine reproductive and respiratory syndrome virus(PRRSV)mainly causes sow abor-tion,stillbirth,mummified fetus and respiratory symptoms in piglets.Since first reported in China in 1996,the virus complexity has increased significantly in more than 20 years of genetic evolution,bringing huge economic losses to the pig industry.In recent years,with the emergence of various PRRSV recombinant virus strains,preventing and controlling this epidemic became increasingly difficult.The purpose of this article is to comprehensively review the genome structure and func-tion of PRRSV,RNA virus recombination mechanism,main types of recombination,and the epi-demic status and recombination for the dominant epidemic PRRSV strains,in order to provide clues for in-depth research on gene recombination of PRRSV,thus providing the theoretical sup-port for formulating scientific prevention and control strategies.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To conduct a comparative analysis of the oxygen depletion and oxygen effect of FLASH irradiation and conventional irradiation by direct measurement of oxygen content.Methods:The oxygen content in different tissues and organs of mice was measured using a phosphorescent probe. A subcutaneous xenograft tumor model in mice was established, to receive electron-beam irradiation at different doses and dose rates. The oxygen depletion of tumor and normal tissue was analyzed, and tumor control was evaluated. The oxygen depletion of conventional irradiation and FLASH irradiation was further analyzed using an in vitro model. The survival fraction (SF) of normal cells after conventional irradiation and FLASH irradiation was calculated using colony formation assay under different partial pressures of oxygen, and the data were fitted to the oxygen enhancement ratio (OER) curve. Results:The mean oxygen content of subcutaneous xenograft tumor in mice was 1.28%, suggesting hypoxia. The mean oxygen content of normal tissue ranged from 3.51% to 6.53%, suggesting physioxia. In animal experiments, oxygen depletion was not observed during conventional irradiation. High-dose-rate (20 Gy/s) and ultra-high-dose-rate (FLASH, 40 Gy/s) irradiation produced oxygen depletion. During FLASH irradiation, with the increase of oxygen content, the oxygen depletion was 0.1-0.2 mm Hg/Gy for tumor tissue and 0.19-0.21 mm Hg/Gy for skin tissue, which tended to stabilize. FLASH irradiation maintained equivalent tumor control compared to conventional irradiation. The tumoricidal effect was significantly enhanced with the increase of oxygen content in the tissue ( t=3.46, P<0.01). In in vitro experiments, the mean oxygen depletion rate was about 0.16 mm Hg/Gy for conventional irradiation and 0.16-0.18 mm Hg/Gy for FLASH irradiation, which did not change significantly with the increase of oxygen content. FLASH irradiation was associated with an oxygen effect. When the partial pressure of oxygen decreased from physioxia to hypoxia, the OER value significantly reduced. Conclusions:Normal tissues and organs are in physioxia, which exhibits a lower oxygen content than that in the air. FLASH irradiation can consume a proportion of oxygen, producing an oxygen effect. When oxygen content decreases, the oxygen depletion rate slows down after FLASH irradiation.

Objective:To summarize the characteristics of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants and evaluate the efficacy and safety of transcatheter PDA closure (TCPC).Methods:This was a retrospective study including five VLBW preterm infants who were diagnosed with hsPDA by echocardiography at Women and Children's Hospital, Qingdao University from January to December 2024 and underwent transcatheter closure after pharmacological therapy failure. Follow-up assessments were conducted at 6 months after operation to evaluate PDA closure status, survival outcomes, and the occurrence of complications. Descriptive statistical analysis was used to summarize the demographic characteristics and clinical data.Results:The cohort comprised three males and two females. The median gestational age was 28 (24-29) weeks, and the median birth weight was 1 000 (670-1 220) g. The median age and birth weight at surgery were 25 (13-36) d and 1 200 (810-1 400) g, respectively. The PDA diameter was 3.8 (2.3-4.1) mm. PDA closure was successfully achieved in all five infants using the Amplatzer Piccolo? occlude, with no major procedure-related complications. All patients were weaned from mechanical ventilation and discharged. At 6-month follow-up, all five infants survived with no residual shunt, left pulmonary artery stenosis, or aortic coarctation on echocardiography.Conclusions:TCPC is feasible and safe for VLBW preterm infants when pharmacological therapy is ineffective or contraindicated. Larger cohorts and extended follow-up are needed to assess long-term outcomes and potential complications.

Objective To design a digital intelligence-driven critical treatment platform to implement integrated treatment procedure inside and outside the hospital and intelligent whole-course managment from pre-hospital emergency care to discharge for critically ill patients.Methods The platform was designed with 5G,IoT,big data and aritificial intelligence techniques and developed with Java language,which adopted Oracle database-based data management and front-end and back-end separation mode,with the front end realized by Vue.js framework and the back end by microservice architecture.There were five functional modules for pre-hospital emergency care,multidisciplinary joint diagnosis and treatment,critical care,quality control management and post-discharge follow-up involved in the platform.Results The platform developed simplified the treatment procedure,enhanced the timeliness of emergency care,decreased the workload of nursing staffs and improved medical service efficiency and working efficiency effectively.Conclusion The platform increases first aid quality and treatment efficiency and provides critically ill patients with high-quality medical experience.[Chinese Medical Equipment Journal,2025,46(1):38-43]

Despite that sleep disturbance and poor neurocognitive performance are common complaints among coronavirus disease 2019 (COVID-19) survivors, few studies have focused on the effect of post-COVID-19 sleep disturbance (PCSD) on cognitive function. This study aimed to identify the impact of PCSD on neurocognitive function and explore the associated risk factors for the worsening of this condition. This cross-sectional study was conducted via the web-based assessment in Chinese mainland. Neurocognitive function was evaluated by the modified online Integrated Cognitive Assessment (ICA) and the Number Ordering Test (NOT). Propensity score matching (PSM) was utilized to match the confounding factors between individuals with and without PCSD. Univariate analyses were performed to evaluate the effect of PCSD on neurocognitive function. The risk factors associated with worsened neurocognitive performance in PCSD individuals were explored using binary logistic regression. A total of 8692 individuals with COVID-19 diagnosis were selected for this study. Nearly half (48.80%) of the COVID-19 survivors reported sleep disturbance. After matching by PSM, a total of 3977 pairs (7954 individuals in total) were obtained. Univariate analyses revealed that PCSD was related to worse ICA and NOT performance (P<0.05). Underlying disease, upper respiratory infection, loss of smell or taste, severe pneumonia, and self-reported cognitive complaints were associated with worsened neurocognitive performance among PCSD individuals (P<0.05). Furthermore, aging, ethnicity (minority), and lower education level were found to be independent risk factors for worsened neurocognitive performance in PCSD individuals (P<0.05). PCSD was related to impaired neurocognitive performance. Therefore, appropriate prevention and intervention measures should be taken to minimize or prevent PCSD and eliminate its potential adverse effect on neurocognitive function.
Humans ; COVID-19/epidemiology* ; Male ; Female ; Sleep Wake Disorders/epidemiology* ; Propensity Score ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Aged ; Risk Factors ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/etiology* ; Neuropsychological Tests

Objective:To investigate the efficacy of a domestically developed small esophageal cooling device in implementing targeted temperature management (TTM) after resuscitation and its impact on organ injury using a porcine model of cardiac arrest and resuscitation.Methods:Thirty healthy male domestic white pigs were randomly divided into four groups using a random number table: sham (S group, n=6), normothermia (NT group, n=8), surface cooling (SC group, n=8), and esophageal cooling (EC group, n=8). The S group underwent only surgical preparation, while the other groups were subjected to 12 minutes of ventricular fibrillation followed by 6 minutes of cardiopulmonary resuscitation to establish cardiac arrest. The S and NT groups maintained a core temperature of (37.5±0.5)°C using a surface blanket. In the SC and EC groups, therapeutic hypothermia was induced post-resuscitation via surface blanket or esophageal cooling catheter to achieve a target temperature of 34°C, maintained the target temperature (34±0.5)°C for 6 hours, followed by controlled rewarming at 0.5°C/h to 37°C. Core temperature was continuously monitored for 12 hours post-resuscitation. Hemodynamic parameters, including stroke volume (SV), global ejection fraction (GEF), extravascular lung water index (ELWI), and pulmonary vascular permeability index (PVPI), were assessed using pulse indicator continuous cardiac output (PiCCO) monitoring. Serum levels of cardiac troponin I (cTnI), neuron-specific enolase (NSE), creatinine (Cr), and intestinal fatty acid-binding protein (IFABP) were measured via ELISA at 2, 6, 12, and 24 hours post-resuscitation. Neurological outcomes were evaluated at 24 hours using the neurological deficit score (NDS) and cerebral performance category (CPC). Continuous variables were analyzed using one-way ANOVA. Results:During TTM, the EC group exhibited a faster cooling rate [(1.52±0.18)°C/h vs. (0.94±0.32)°C/h, P<0.05] and shorter time to target temperature [(2.32±0.43) h vs. (3.78±0.82) h, P<0.05] compared to the SC group, with comparable maintenance and rewarming ( P>0.05). Compared to the S group, the NT, SC, and EC groups demonstrated significant post-resuscitation multi-organ injury, characterized by reduced SV and GEF, elevated ELWI and PVPI, and increased serum cTnI, NSE, Cr, IFABP, NDS, and CPC scores (all P<0.05). Relative to the NT group, the SC and EC groups showed improved SV (at 1 h post-resuscitation), GEF (at 1, 2, 4, and 6 h), ELWI (at 12 h), and reduced cTnI and NSE (at 6 h), Cr and IFABP (at 2 h), and NDS and CPC (at 24 h) (all P<0.05). Compared to the SC group, the EC group exhibited lower PVPI (at 12 h), reduced cTnI, Cr, and IFABP (at 2 h), decreased NSE (at 2, 12, and 24 h), and improved NDS (at 24 h) (all P<0.05). Conclusions:In a porcine model of cardiac arrest and resuscitation, the domestic esophageal cooling device facilitated rapid induction, stable maintenance, and controlled rewarming during TTM, outperforming traditional surface cooling. This approach demonstrated superior organ protection, warranting further investigation.

Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of the EGF gene,including rs11569017(A>T),rs2237051(A>G),rs3733625(C>T),and rs4444903(A>G),and the risk of non-small cell lung cancer(NSCLC)in a Han population of Yunnan.Methods A total of 439 patients with NSCLC and 520 healthy controls were recruited in Yunnan Province between January 2022 and December 2023.Genotyping of four SNP loci in the EGF gene was performed using TaqMan probes,followed by analysis of allele,genotype,genetic model,and haplotype distribution frequencies between NSCLC and control groups.Stratified analyses were further conducted based on NSCLC pathological types and clinical stages.Results The rs2237051 locus showed significant differences in allele(P=0.011)and genotype(P=0.042)frequencies between the squamous cell carcinoma(SCC)group and the control group.The frequency of the A allele was lower in the SCC group than in the control group(OR=0.71,95%CI 0.54～1.85),but there was no difference after Bonferroni correction(P>0.0125).Under the log-additive model,the rs2237051-2G/G+A/G genotype was associated with an increased risk of SCC(P=0.01;OR=1.42,95%CI 1.08～1.86).However,the association lost statistical significance after Bonferroni correction(P>0.0125).The haplotype rs11569017-rs2237051-rs3733625-rs4444903 has no difference between the two groups(P>0.0125).The stratified analysis revealed no significant associations between the genetic loci and different disease stages(P>0.0125).Conclusion In the Yunnan Han population,the individuals carrying the rs2237051-A allele of the EGF gene have a significantly lower risk of squamous lung cancer,but further functional experiments are needed to verify the protective mechanism.

Objective:To observe the expression level of long noncoding RNA RP11-97C16.1 in bladder cancer tissues and its relationship with the survival time of bladder cancer patients, and to explore the role and potential molecular mechanism of RP11-97C16.1 in the proliferation of bladder cancer cells.Methods:The expression difference of RP11-97C16.1 in bladder cancer tissue and adjacent tissue was analyzed by TCGA database, and the relationship between the expression level of RP11-97C16.1 and the survival time of bladder cancer patients was analyzed by GEPIA database. The expression of RP11-97C16.1 in four bladder cancer cell lines (T24, MGH-U3, J82, UM-UC-3) was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The UM-UC-3 cells were divided into RP11-97C16.1 group and control group, and the transfectants were pcDNA-RP11-97C16.1 plasmid and negative control plasmid, respectively. The expression levels of RP11-97C16.1 and miR-3687 were detected by RT-qPCR. The viability and proliferation ability of UM-UC-3 cells were detected by cell counting kit-8 (CCK8) and colony formation assay. The complementary relationship between RP11-97C16.1 and miR-3687 was verified by dual-luciferase reporter gene assay. The expression levels of Cyclin E2, CDK2, CDK4, CDK6 and Cyclin D2 were detected by Western blotting. Measurement data were expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with adjacent tissues, the expression of RP11-97C16.1 in bladder cancer tissues was significantly decreased ( P<0.01). Compared with patients with lower expression of RP11-97C16.1, patients with higher expression of RP11-97C16.1 had longer overall survival time ( P<0.01). Compared with the SV-HUC-1 cell line, the expression of RP11-97C16.1 was significantly decreased in the four bladder cancer cell lines ( P<0.01). In UM-UC-3 cells in which RP11-97C16.1 was upregulated, the expression of miR-3687 was decreased ( P<0.01). Compared with the control group, up-regulation of RP11-97C16.1 could significantly reduce the proliferation ability of UM-UC-3 cells ( P<0.05), and decrease the number of bladder cancer cell colonies ( P<0.01). RP11-97C16.1 could target and bind miR-3687 ( P<0.01). Compared with the control group, overexpression of RP11-97C16.1 could significantly decreased the expression of Cyclin E2, CDK2, CDK4, CDK6, and Cyclin D2 proteins. Conclusions:The expression of RP11-97C16.1 is low in bladder cancer tissue, and patients with higher expression of RP11-97C16.1 have a longer survival time. Up-regulation of RP11-97C16.1 can down-regulate the expression of miR-3687, thereby inhibiting the proliferation of bladder cancer cells UM-UC-3.