ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg^-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg^-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.

Objective To evaluate the clinical outcome of kidney transplantation from donation after brain death(DBD)donors complicated with acute kidney injury(AKI).Methods Clinical data of 216 DBD donors were retrospectively analyzed,and they were divided into the AKI group(n=69)and control group(n=147)according to the Kidney Disease:Improving Global Outcomes(KDIGO)guidelines.Donors in the AKI group were further divided into the KDIGO stage 1 and stage 2-3 subgroups.One hundred and thirty-five recipients were assigned into the AKI group and 288 recipients in the control group.Postoperative recovery of renal function and clinical outcomes of the recipients were recorded.The risk factors of delayed graft function(DGF)were identified.Results The highest serum creatinine(Scr)level,Scr level before procurement,the highest blood sodium level and blood sodium level before procurement in the AKI group were higher than those in the control group.The application duration of vasopressors in the AKI group was longer than that in the control group.In the AKI group,the amount of fluid resuscitation within 48 h was higher,the HCO3-level at admission was lower,and the incidence of diabetes insipidus and hypotension was higher than those in the control group.The highest Scr level and the Scr level before procurement in KDIGO stage 2-3 donors were significantly higher than those in KDIGO stage 1 counterparts(all P＜0.05).Compared with the control group,the incidence of DGF and acute rejection was higher,the proportion of continuous renal replacement therapy was higher,the Scr level within postoperative 90 d was higher,and the urine amount within postoperative 3 d was less than those of recipients in the AKI group.Compared with KDIGO stage 1 recipients,KDIGO stage 2-3 recipients had higher Scr levels at postoperative 3,4,5 and 15 d,and less urine amount at postoperative 2 d(all P＜0.05).Univariate analysis showed that donor age,the highest Scr level,the highest blood sodium level and the amount of fluid resuscitation within 48 h were the risk factors for DGF in recipients after kidney transplantation.Multivariate analysis showed that donor age was the independent risk factor for DGF in recipients after kidney transplantation(all P＜0.05).Conclusions For the application of DBD donors complicated with AKI,active organ maintenance should be performed to alleviate AKI.It exerts no effect upon graft function and survival rate at postoperative 6 months,which may achieve equivalent efficacy as non-AKI donors and may be used as a source of extended criteria donor kidneys.

Objective:To evaluate the effect of gender factors on the potency of oxycodone inhibiting responses to laryngeal mask airway (LMA) insertion in patients.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-59 yr, with a body mass index of 18-28 kg/m 2, scheduled for elective surgery with general anesthesia using LMA, were divided into 2 groups according to gender: male group (group M) and female group (group F). The dose of oxycodone was determined by using modified Dixon′s up-and-down method. Oxycodone 0.1 mg/kg was intravenously infused in the first patient of each group, and propofol 3 μg/ml was simultaneously given by target-controlled infusion. When bispectral index value ≤60 after the equilibration between effect-site concentration and plasma concentration was achieved, cisatracurium 0.2 mg/kg was intravenously injected, and 3 min later the LMA was inserted. When the response to LMA insertion was positive, the dose of oxycodone was increased in the next patient, otherwise the dose was decreased, and the ratio between the two successive doses was 1.1. The process was repeated until the 7th turning point occurred. The positive response to LMA insertion was defined as an increase in the maximum heart rate or in the maximum mean arterial pressure >20% of the baseline value with 2 min after insertion. The median effective dose (ED 50) and 95% confidence interval of oxycodone inhibiting responses to LMA insertion were calculated by the probit analysis. Results:Twenty-eight cases were finally included in M group and 25 cases in F group. The ED 50 (95% confidence interval) of oxycodone was 0.105 (0.091-0.115) mg/kg in group M and 0.087 (0.082-0.094) mg/kg in group F. The ED 50 of oxycodone was significantly higher in group M than in group F ( P<0.001). Conclusions:The effect of oxycodone inhibiting responses to nociceptive stimulation induced by LMA insertion is related to gender factors, with increased potency in females.

Objective:To explore the genetic etiology of pediatric intensive care unit (PICU) mortality cases and summarize their clinical characteristics.Methods:This was a retrospective cohort study. The study population consisted of 234 children who died within 7 d after admitted to the PICU of Children′s Hospital of Fudan University from January 2017 to December 2021. The clinical diagnoses, laboratory test results, and genetic testing results were collected. These patients were divided into the pathogenic gene variation positive (PGVP) group and the pathogenic gene variation negative (PGVN) group according to the results of genetic testing. The Mann-Whitney U test and Pearson′s chi-square test or Fisher′s exact probability method were used to compare the clinical characteristics between the groups. Results:A total of 234 cases were enrolled, including 139 (59.4%) males and 95 (40.6%) females. The age at death was 1.0 (0.4, 3.7) years old and the length of PICU stay was 16 (6, 33) days. There were 62 cases (26.5%) PGVP, and the mutated pathogenic genes included immune genes (23 cases (37.1%)), metabolic genes (11 cases (17.7%)), neuromuscular genes (11 cases (17.7%)), cardiovascular genes (4 cases (6.5%)), and genes of other systems (13 cases (21.0%)). The age at death in PGVP cases was significantly lower than in PGVN cases (0.6 (0.3, 1.4) vs. 1.3(0.5, 4.3) years old, Z=3.85, P<0.001). Compared with the PGVN group, the PGVP group had a higher incidence of family history and chronic complex conditions (CCC) than the PGVN group (6.5% (4/62) vs. 0.6% (1/172) and 93.5% (58/62) vs. 76.2% (131/172), χ2=8.87, P=0.018 and 0.003, respectively). Children in the PGVP group were admitted with higher incidence of severe infection, decreased consciousness or coma, moderate-to-severe anemia, thrombocytopenia, protracted diarrhea, and abnormalities in muscle strength or tone than those in the PGVN group (74.2%(46/62) vs. 45.9%(79/172), 50.0%(31/62) vs. 35.5%(61/172), 32.3%(20/62) vs. 18.0%(31/172), 21.0%(13/62) vs. 10.5%(18/172), 25.8%(16/62) vs. 4.1%(7/172), 16.1%(10/62) vs. 5.2%(9/172), χ2=14.63, 4.04, 5.41, 4.37, 24.30, 7.25, all P<0.05). Pathogenic genes that occurred more than twice included IL2RG (5 cases), SMN1 (4 cases), and SH2D1A (3 cases, including 2 single gene varients and 1 copy number varient). Conclusions:Among the deceased cases in the PICU, the main genetic causes are immune-related, metabolic, and neuromuscular genetic disorders. Critically ill children with a family history, CCC, and early features such as severe infections, decreased consciousness or coma, moderate to severe anemia, thrombocytopenia, protracted diarrhea, or abnormalities in muscle strength or tone should be closely monitored and undergo early genetic testing.

Objective Based on the multi-software visual analysis of the literature on the effect of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway on rheumatoid arthritis in the past decade,the development trend and research hotspot in this field are summarized.To provide researchers with new directions and ideas to promote the innovative development of the field.Methods The literatures related to JAK/STAT signaling pathway in rheumatoid arthritis were collected from the Web of Science Core Collection database from 2013 to 2023.CiteSpace and VOSviewer software were used to analyze the number of publications,countries,authors and keywords of 354 articles retrieved.Results The number of published papers in this field continues to increase.According to the author's research direction,the presentation of high-frequency words,and the attention to the preface and hot topics,it is suggested that this field focuses on gene expression,immune mechanism,inflammatory mechanism,pathway inhibitors,drug therapy,etc.Future research will focus on the safety,mechanism and controlled trials of pathway inhibitors and antirheumatic drugs.Conclusion The effect of JAK/STAT signaling pathway on rheumatoid arthritis has attracted much attention in the past,present and future.There are differences in the research of different teams in this field,and the regional development is unbalanced,suggesting that we should strengthen cooperation and exchanges,focus on the international frontier,and carry out more high-quality research to promote the development and progress of this field,and provide clinical basis.

Osteoporosis (OP) is a prevalent metabolic bone disease with a complex pathogenesis that has not yet been fully elucidated. Recent studies have revealed that the Toll-like receptor 4 (TLR4) signaling pathway plays a significant role in the development and progression of OP. TLR4, a crucial immune receptor primarily expressed in immune cells, is involved in inflammatory responses and immune regulation. The TLR4 signaling pathway influences bone metabolism and remodeling through multiple mechanisms. Therefore, investigating the role of the TLR4 signaling pathway in OP is of great significance for its prevention and treatment. Research targeting the TLR4 signaling pathway provides novel insights and approaches for OP therapy. Future studies should further explore the mechanisms of the TLR4 signaling pathway, develop therapeutic agents that modulate this pathway, and validate their efficacy in OP through clinical trials, thereby offering more options for the clinical management of OP.

Objective:To investigate the availability and safety of a domestic disposable digital flexible cystoscope compared with a reusable Olympus digital flexible cystoscope in cystoscopy and removal of double J stent.Methods:From August 2018 to March 2019, patients were enrolled in this prospective, open, multicenter, randomized, parallel positive controlled clinical trial study, which were from department of Urology in Renmin Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University and the First Affiliated Hospital of Guangzhou Medical University. The experimental group and control group were assigned into a 1∶1 ratio by random table method. Inclusion criteria included age≥18 years and have indications for cystoscopy or removal of double J stent. Exclusion criteria included patients having acute genitourinary tract infection, having tuberculous bladder contracture, bladder capacity less than 50ml, having urethrostenosis, female menstrual period, pregnancy and lactation, having difficulty for lithotomy position, having serious cardio-cerebrovascular disease and liver or kidney dysfunction. A domestic disposable digital flexible cystoscope was adopted in the experimental group, whereas a reusable Olympus digital flexible cystoscope was used in the control group. Acceptability of image was defined as primary availability indicator, while success rate of working and performance score were defined as secondary availability indicators and mean operating time was calculated for cystoscopy only and cystoscopy plus removal of double J stent respectively, yet rate of adverse event as well as rate of equipment defects were sorted as safety indicators.Results:A total of 188 cases which were listed in per protocol set completed the clinical trial study successfully. There were 95 cases in the experimental group and 93 cases in the control group. Acceptability of image was 93.68%(89/95) and 96.77%(90/93) respectively in two groups( P=0.52). Success rate of working was 100.00%(95/95) and 98.92%(92/93) respectively in two groups ( P=0.49). Performance score was 14.41±0.93 and 14.56±0.84 respectively in two groups ( P=0.23). Mean operating time (MOT) only for cystoscopy was (15.3±2.6) min and (15.4±3.3)min respectively in two groups ( P=0.93), while MOT for cystoscopy plus removal of double J stent was (21.0±3.2) min and (21.7±3.9) min respectively in two groups ( P=0.69). Rate of adverse event was 8.42%(8/95) and 9.68%(9/93) respectively in two groups( P=0.76). There was no equipment defects in both groups. Conclusions:There is no statistical difference in acceptability of image, success rate of working, performance score, mean operating time for cystoscopy or removal of double J stent, rate of adverse events and rate of equipment defects. A domestic disposable digital flexible cystoscope has shown non-inferiority in the availability and safety compared with a reusable Olympus digital flexible cystoscope.

Objective:To explore the association analysis of clinical characteristics and prognoses with cerebrospinal fluid antibody titer in patients with anti N-methyl- D-aspartic acid (NMDA) receptor encephalitis. Methods:Thirty-eight patients with anti-NMDA receptor encephalitis, admitted to our hospital from June 2014 to March 2019, were chosen. According to the titer results of anti-NMDA receptor antibodies reported by the first cerebrospinal fluid specimens, they were divided into low antibody titer group (antibody titer 1:10 and 1:32) and high antibody titer group (antibody titer 1:100 and 1:320). The clinical characteristics and prognoses of these patients were compared.Results:Of these 38 patients, 14 were into the group of low antibody titer, and 24 were into the group of high antibody titer. Patients in the low antibody titer group had significantly higher incidences of headache and laloplegia, and statistically lower serum antibody positive rate ( P<0.05). There were no significant differences between the two groups in other prodromal symptoms including fever, respiratory symptoms and life events, other common clinical manifestations including psychobehavioral abnormalities or cognitive impairment, seizures, motor disorders and decreased consciousness level, staying in ICU or not, intubating endotracheal tube or not, length of stay in ICU, time from symptom onset to definite diagnosis, and occurrence of complications, skull MRI, EEG, and lab results, modified Rankin scale (mRS) scores at discharge, time required to recover to mRS score of 0-1 after discharge, and mRS scores at follow-up. Conclusion:Cerebrospinal fluid antibody titer has limited significance in evaluating disease severity and guiding diagnosis and treatment in patients with anti-NMDA receptor encephalitis at acute stage.

Objective:To explore optimum surgical treatment of ureteral strictures after ureteroscopic holmium laser lithotripsy.Methods:The clinical data of 113 patients with ureteral stricture after ureteroscopic holmium laser lithotripsy from December 2014 to December 2019 were analyzed retrospectively. Of all the patients, there were 73 males and 40 females(aged from 31 to 68) with the mean age of 49 years. The mean length of ureteral stricture was 15mm (from 5mm to 25mm). The mean time since the last holmium laser lithotripsy was 6 months (from 3months to 10 months). According to the different treatment of stenosis, 113 patients were divided into endourological treatment group (34 patients) and reconstruction group(79 patients). According to the different surgical methods, endourological treatment group was divided into ureteral balloon dilatation (18 patients) and ureterotomy (16 patients). Reconstruction group was divided into laparoscopic surgery and open surgery, whose were ureteral stenosis resection and anastomosis. Patients were followed up closely postoperatively. Therapeutic success was defined as disappeared hydronephrosis, and unobstructed anastomosis. Success rate, operation time, postoperative changes of hemoglobin, hospital stay and the incidence of postoperative complications were measured.Results:The follow-up time ranged from 5 months to 53 months, with a median time of 18 months. There was no significant difference in age, sex, BMI, location of ureteral stricture, side of stricture and degree of hydronephrosis between endourological treatment group and reconstruction group( P>0.05). The length of ureteral stricture in reconstruction group was significantly longer than that in endourological treatment group (10.3±4.2 mm vs. 17.2±7.8mm, P<0.001). Although the operation time, postoperative changes of hemoglobin, hospital stay and the incidence of postoperative complications were lower in the endourological treatment group compared to reconstruction group ( P<0.001), the overall success rate of the reconstruction operation was significantly higher than that in endourological treatment group (96.2% vs. 61.8%, P<0.001). Furthermore, there was no significant difference in the success rate between laparoscopic surgery group and open surgery group (95.3% vs.97.2%, P<0.05), and there was no significant difference between the balloon dilatation group and the stenosis internal ureterotomy group (66.7% vs.56.3%, P<0.05).113 cases were followed up for an average of 18 (5-53) months. Conclusions:For the treatment of ureteral stricture after ureteroscopic holmium laser lithotripsy, the success rate of reconstruction group (laparoscopic surgery and open surgery)was significantly higher than that of endourological surgery (balloon dilatation and internal ureterotomy). Reconstruction surgery is the optimum surgical treatment to treat ureteral stricture after ureteroscopic holmium laser lithotripsy.

Objective: To investigate the value of diagnostic digital flexible ureteroscopy in patient with hematuria from unilateral upper urinary tract. Methods: A retrospective analysis was made in consecutive 140 cases, including 94 males and 46 females, who are considered for hematuria from unilateral upper urinary tract in Renmin hospital of Wuhan University from January 2014 to February 2019.Their age ranged from 22 to 89 years, with mean of 62.3 years. The mean BMI was 24.6 kg/m²(ranging 22.1-28.2 kg/m²). All patients complained about the continuously or intermittently gross hematuria. 29 cases (20.7%) complained about the flank pain, as well. All cases were examined by urinary sonography, CTU and voided urine cytology preoperatively. Occupying lesion was found in 47 case by sonography including suspected diagnosis. Upper tract urothelial carcinoma(UTUC) was diagnosed in 63 cases by CTU including suspected diagnosis.Voided cytology was positive in 17 cases. Concomitant bladder or urethral lesions were excluded by cystoscopy. Hematuria was confirmed from left side in 82 cases(58.6%) and from right side in 58 cases(41.4%). Diagnostic digital flexible ureteroscopy were performed under general anethesia strictly according to 'No touch technique’. Biopsy for suspicious lesions as well as selective in situ cytology were acquired during ureteroscopy. Results: All patients accepted the examination successfully. The duration of follow-up ranged from 3 to 37 months, with mean of 13 month. Benign lesions were found in 71 cases(50.7%) while malignant lesions were identified in 69 cases(49.3%). Benign lesions included 39(54.9%)minute venous rupture, 12 (16.9%)hemangioma, 3 (4.2%)varix and 11 (15.5%)no obvious lesion. The overall success rate of ureteroscopic treatment was 66(93.0%) whereas recurrence rate after treatment was 8(11.3%). Malignant lesions including 67(97.1%) cases with UTUC and 2 cases with squamous carcinoma. The radical nephroureterectomy(RNU)and bladder sleeve resection was performed in all cases. To 67 cases with UTUC, the overall identification rate of urinary sonography, CTU, voided urine cytology, selective in situ cytology and diagnostic digital flexible ureteroscopy was 41(61.2%), 61(91.0%), 13(19.4%), 38(56.7%) and 63(94.0%) respectively. Identification rate of selective in situ cytology was superior to voided cytology(P<0.01) while diagnostic digital flexible ureteroscopy was no significant difference compared with CTU. The concordance of pathological grade between biopsy and final resection specimen was 73.1%.The concordance of low grade was 93.3% whereas high grade was 56.8%. Up-grading was found in 16(23.9%) cases while down-grading was found in 2(3.0%) cases. Intravesical recurrence was affirmed in 11(16.4%) cases during follow-up. Conclusions Diagnostic digital flexible ureteroscopy may not only present qualitative as well as localized evidence for etiological diagnosis of hematuria from unilateral upper urinary tract, but also provides strategy choice for treatment.