ObjectiveTo investigate the ability of clinically isolated， Helicobacter pylori （H. pylori）-specific gene polymerase chain reaction （PCR）-positive gastric， vaginal， and fecal Candida to release H. pylori. MethodsResuscitate 4 strains of H. pylori -specific 16S rDNA and ureA gene PCR-positive Candida strains isolated in laboratory from clinical sources， including 1 strain of gastric Candida， 1 strain of fecal Candida， 2 strains of vaginal Candida and the standard Candida albicans strain ATCC10231 （Ca10231）. The presence of H. pylori-specific ureA in the 5 strains of Candida isolates was confirmed by PCR. The aforementioned strains of Candida and H.pylori were inoculated into urea medium and cultured in a constant temperature incubator at 37 ℃. The color change of the medium was observed daily. A change in the medium's color from yellow to red indicated the presence of urease activity. Then， the five strains of Candida and H. pylori were co-incubated with the magnetic beads coated with H. pylori antibodies respectively. Scanning electron microscopy （SEM） was employed to observe the presence of bacilli adsorbed on the surface of the magnetic beads. PCR was used to detect the presence of H.pylori-specific 16S rDNA and ureA genes on magnetic beads. ResultsThe PCR analysis of the ureA gene in the four Candida isolates was positive， whereas the Ca10231 strain tested negative. Upon culturing the four Candida isolates on urea medium， the medium color changed from yellow to red which was determined to be urease positive， while the medium containing Ca10231 remained unchanged， which was urease negative. SEM revealed that bacilli could be observed on the surface of magnetic beads co-incubated with the 4 strains of Candida of clinical origin and H.pylori isolate. Specifically， PCR testing of the magnetic beads co-incubated with one vaginal Candida， one gastric Candida and H.pylori isolate showed positive results for the 16S rDNA and ureA genes of H. pylori； however， the PCR tests for the two genes were negative for the magnetic beads co-incubated with the other two Candida isolate. ConclusionThis study demonstrates that H. pylori-specific genes Candida can release H. pylori.

Icaritin(ICT)is an 8-isopentenylflavonoid,which is the main effective component of the tra-ditional Chinese medicine Epimedium.Previously,we found that Icaritin inhibits the growth of glioblasto-ma(GBM)cells.Herein we aim to study the in vivo anti-GBM effectiveness of Icaritin and explore its mechanism.The results of MTT assay,flow cytometry,comet assay and cellular immunofluorescence as-say in vitro showed that ICT inhibited the proliferation of four kinds of GBM cells,U87,U251,U118 and A172,induced early apoptosis(P＜0.001)and late apoptosis(P＜0.05)in U87 cells,induced DNA damage in U87 cells,and blocked the growth of U87 cells at the G0/G1 phase(P＜0.0001)in a concen-tration-time-dependent manner.In vivo subcutaneous tumor transplantation tumor experiments showed that feeding 200 mg/kg(P＜0.01)and 400 mg/kg(P＜0.001)ICT had a significant inhibitory effect on the growth of GBM subcutaneous tumors,and had no significant toxic effects on heart,liver,spleen,lung and kidney tissues.The results of network pharmacological analysis,molecular docking and cellular thermodynamic experiments showed that there were 26 possible target proteins between ICT and GBM,a-mong which the expression of p53 in GBM tissues was significantly(P＜0.001)higher than in normal tis-sues,and the binding energy of ICT and p53 was lower;cellular thermodynamic experiments verified that ICT significantly enriched the level of p53 in the living cells of GBM,which indicated that ICT could tar-get p53.The expression of key proteins in the DNA damage repair and apoptosis-associated FOXO signa-ling pathway was detected by ICT.The results showed that the expression of ATR(P＜0.01),P53(P＜0.001),P21(P＜0.05)and γ-H2AX(P＜0.05)was up-regulated,whereas the expression of Cyc-lin E1(P＜0.01),E2F1(P＜0.05),CDK2(P＜0.01),Rb(P＜0.001),p-Rb(P＜0.0001)and WRN(P＜0.0001)expression were down-regulated.There was no significant change in the expres-sion of FOXO 1 in the FOXO pathway or a significant down-regulation of its phosphorylation level.This study demonstrated that ICT could effectively inhibit the growth of GBM cells in vivo.It targets p53 to regulate the DNA damage repair pathway and FOXO signaling pathway to induce GBM cell cycle arrest and apoptosis.

BACKGROUND:Spinal cord injury often leads to neurogenic bladder with hyperreflexia of the forced urethral muscle,but there is a lack of clear understanding of its pathogenesis and treatment,and establishing a stable and reliable animal model has an important impact on revealing its pathomechanisms and exploring therapeutic approaches.OBJECTIVE:To investigate the effect of the number of times to urinate on neurogenic model rats after complete spinal cord transection in order to improve the postoperative survival and modeling rate of neurogenic model rats.METHODS:Out of 46 female Sprague-Dawley rats,6 were selected as the sham-operated group using the random number table method,and the remaining 40 rats were randomly divided into 0,1,3,and 5 times daily urination groups after complete spinal cord transection modeling,with 10 rats in each group.The residual urine volume was measured every 3 days within 19 postoperative days,and the survival and modeling were observed on the 19th day after the operation,and urodynamics tests and contraction experiments of isolated forced urethra muscle strips were performed.RESULTS AND CONCLUSION:(1)Survival and modeling rate:there was 10%survival rate and 10%modeling rate in the group of 0 times daily urination;20%survival rate and 10%modeling rate in the group of 1 time daily urination;70%survival rate and 70%modeling rate in the groups of 3 and 5 times daily urination.(2)Residual urine volume:compared with the sham-operated group,the residual urine volume of the groups of 3 and 5 times daily urination was significant increased on postoperative days 3,6,9,12,and 15(P<0.01);the residual urine volume of the groups of 3 and 5 times daily urination was increased on the 18th day after surgery(P<0.05).Compared with the 3 times daily urination group,the residual urine volume was decreased in the 5 times daily urination group on the 6th day after surgery(P<0.05),while there was no significant difference in the residual urine volume between the 3 and 5 times daily urination groups on the 3rd,9th,12th,15th,and 18th days after surgery.(3)Urodynamics:Compared with the sham-operated group,the differential pressure at the point of leakage was significantly reduced(P<0.01)and the maximal volume was significantly increased(P<0.01)in the 3 and 5 times daily urination groups.There was no statistical difference in the differential pressure at the point of leakage and the maximal volume between the 3 and 5 times daily urination groups.(4)Muscle-strip contraction test of isolated detrusor muscles:Compared with the sham-operated group,the contraction amplitude and frequency of detrusor muscle strips were significantly reduced in the 3 and 5 times daily urination groups(P<0.01).There was no statistically significant difference in the contraction amplitude and frequency of detrusor muscle strips between the 3 and 5 times daily-urination groups.In conclusion,assisted urination is one of the keys to establish a successful neurogenic model of urethral reflexes,and there is no significant difference in the effects of urinating 3 or 5 times a day on the neurogenic model.It is recommended to urinate at least 3 times a day based on the actual workload and the modeling rate.

Objective To observe the effects of electroacupuncture(EA)on TGF-β1/Smads signaling pathway and epithelial-mesenchymal transition(EMT)related proteins in rats with neurogenic bladder(NB)after spinal cord injury;To explore the possible mechanism of EA in improving NB fibrosis.Methods Totally 36 female SD rats were randomly selected,with 10 rats in the sham-operation group and the remaining 26 rats undergoing complete transection of the spinal cord beneath the T8 vertebrae to establish a NB rat model.The modeling rats were randomly divided into model group and EA group,with 10 rats in each group.EA group was applied to"Ciliao","Zhongji"and"Sanyinjiao",20 min per time,once a day for 7 days.The general condition of the rats in each group was observed,the ultrasound index of the bladder was detected by ultrasound technique,the bladder function of the rats was detected by urodynamics,the body mass of the rats and the wet weight of the bladder were recorded,and the bladder index was calculated.HE staining was used to observe bladder tissue morphology,the degree of bladder tissue fibrosis and bladder wall thickness were detected by Masson staining.The positive expressions of E-cadherin,N-cadherin and Vimentin in bladder tissue were detected by immunohistochemistry.The protein expressions of TGF-β1,p-Smad2/3,E-cadherin,N-cadherin and Vimentin were detected by Western blot.Results Compared with the sham-operation group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the model group significantly increased(P<0.001),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly increased(P<0.001),the bladder index increased significantly(P<0.001),the bladder epithelial cells were thickened and arranged irregularly,the bladder collagen volume fraction and bladder wall thickness significantly increased(P<0.001),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue increased(P<0.01),and the expression of E-cadherin decreased(P<0.001).Compared with the model group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the EA group decreased significantly(P<0.05),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly decreased(P<0.05),the bladder index significantly decreased(P<0.05),the thickness of the bladder epithelial cell layer became thinner and arranged more neatly,and the bladder collagen volume fraction and bladder wall thickness of the bladder were significantly reduced(P<0.05),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue significantly decreased(P<0.05),and the expression of E-cadherin significantly increased(P<0.05).Conclusion EA may reduce the EMT of bladder epithelial cells and decrease the degree of bladder tissue fibrosis by inhibiting the activation of the TGF-β1/Smads signaling pathway,thereby improving bladder function in NB rats after spinal cord injury.

Objective:To investigate the early right heart function management strategy and prognosis after left ventricular assist device(LVAD) implantation in patients with preoperative right ventricular dysfunction.Methods:A retrospective study was conducted. From March 2022 to April 2024, a total of 28 patients with end-stage heart failure underwent LVAD implantation at Nanjing First Hospital and were admitted to the intensive care unit(ICU) after surgery. Among them, patients with preoperative right ventricular dysfunction were enrolled. All patients were implanted with Corheart 6 implantable left ventricular assist device. The clinical data, occurrence of postoperative right heart failure and postoperative survival situations of enrolled patients were collected and analyzed.Results:A total of 12 patients were included in this study, including 11 males and 1 female, the mean age was(58.4±7.6) years old. Upon postoperative admission to ICU, the most commonly used positive inotropic agent was epinephrine(9 cases), followed by dobutamine(8 cases). By the second day after surgery, the most frequently utilized vasoactive medications were epinephrine and phosphodiesterase type Ⅲ inhibitors, both with 9 cases of usage. None of the enrolled patients utilized temporary mechanical circulatory assist devices. The LVAD pump speed of the patients enrolled in the study was set at approximately 2 700 revolutions per minute, and the pump flow was approximately 3 liters per minute. During the first two days after the operation, the fluid balance of the enrolled patients ranged from(-523.4±775.6)ml to(-1 248.0±1 023.9)ml. At 48 h following the operation, the mean pulmonary artery pressure(MPAP)[(26.2±4.8) mmHg vs.(32.1±6.5) mmHg(1 mmHg=0.133 kPa), P=0.042] and the pulmonary artery wedge pressure(PAWP)[(15.6±5.5)mmHg vs.(24.9±5.9) mmHg, P=0.003) ] of the enrolled patients were significantly decreased compared to preoperative levels, while the cardiac index(CI) was significantly improved[(2.7±0.2)L·min -1·m -2 vs.(2.1±0.5)L·min -1·m -2,P=0.024]. Echocardiography showed that the left atrial diameter(LAD)[(51.5±7.6)mm vs.(57.2±9.0)mm, P=0.005] and left ventricular end diastolic diameter(LVDd)[(73.5±11.5)mm vs.(78.3 ± 12.3)mm, P=0.012) ] were significantly reduced post LVAD implantation as compared to before LVAD implantation, while there was no significant difference in tricuspid annular plane systolic excusion(TAPSE). Postoperative total bilirubin(TBIL) decreased significantly compared to preoperative levels[(15.5±5.0)μmol/L vs.(27.5±17.0)μmol/L, P=0.038]. Three patients experienced right heart failure after the LVAD implantation, with an incidence rate of 25%. Nevertheless, the right heart failure was rectified during the ICU treatment period. The mean ICU treatment time for all enrolled patients was(8.6±2.9) days, the average postoperative hospital stay was(24.3±4.8) days. All enrolled patients survived at 3 months after LVAD implantation. Conclusion:Despite the presence of right ventricular dysfunction in patients before LVAD implantation, with strict fluid management, reasonable LVAD parameters, and appropriate vasoactive drugs, they are able to smoothly pass through the perioperative period, achieve the goals of left ventricular decompression, increase cardiac output, improve perfusion of the end organs, and obtain favorable short-term therapeutic effects.

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

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 compare the clinical efficacies of extrapleural internal fixation and transthoracic internal fixation in the treat-ment of thoracic tuberculosis.Methods A total of 70 patients with thoracic tuberculosis(T4 to T10)who were admitted to our hospital from June 2018 to June 2023 were enrolled,and their clinical data were retrospectively analyzed.The 35 patients treated with extrapleural internal fixation were included in the extrapleural group,and the other 35 patients treated with transthoracic internal fixation were included in the transthoracic group.The operation time,intraoperative blood loss,bone graft fusion time,kyphotic angle before and after operation,visual analogue scale(VAS)and Oswestry disability index(ODI)scores after operation,postoperative complications and recurrence were compared between the two groups.Results Compared with the transthoracic group,the operation time and bone graft fusion time were significantly shortened,and the intraoperative blood loss was significantly reduced in the extrapleural group,with statistically significant differences(P<0.05).The postoperative kyphotic angles of the two groups were smaller than those before operation,the postoperative kyphotic angle of the extrapleural group was smaller than that of the transthoracic group,and the differences were statistically significant(P<0.05).The VAS score 7 days after operation of the extrapleural group was lower than that of the transthoracic group,and the difference was statistically significant(P<0.05).The ODI score 1 month after operation of the extrapleural group was lower than that of the transthoracic group,and the difference was statistically significant(P<0.05).The incidence of postoperative complications in the extrapleural group(0)was lower than that in the transthoracic group(34.28%),and the difference was statistically significant(P<0.05).Conclusion Extrapleural internal fixation has the advantages of short time,less bleeding and less trauma in the treatment of thoracic tuberculosis,but it is difficult to completely remove the lesions.Transthoracic internal fixation can completely remove the lesion,but the surgical trauma is large.The choice of clinical operation plan should be comprehensively considered according to the specific condition of the patients,the location of the lesion,and the condition of the lung,so as to achieve the best treatment effect.

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*