In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Background::Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. 18F-prostate specific membrane antigen positron emission tomography/computerized tomography ( 18F-PSMA PET/CT) has several advantages over 68Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of 18F-PSMA PET/CT for lymph node staging in medium/high-risk PCa. Methods::We searched the EMBASE, PubMed, Cochrane library, and Web of Science databases from inception to October 1, 2022. Prostate cancer, 18F, lymph node, PSMA, and PET/CT were used as search terms and the language was limited to English. We additionally performed a manual search using the reference lists of key articles. Patients and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included studies. Sensitivity, specificity, the positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence interval (CI) were used to evaluate the diagnostic value of 18F-PSMA PET/CT. Stata 17 software was employed for calculation and statistical analyses. Results::A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this meta-analysis. At the patient level, the results of each consolidated summary were as follows: sensitivity of 0.57 (95% CI 0.39-0.73), specificity of 0.95 (95% CI 0.92-0.97), PLR of 11.2 (95% CI 6.6-19.0), NLR of 0.46 (95% CI 0.31-0.68), DOR of 25 (95% CI 11-54), and AUC of 0.94 (95% CI 0.92-0.96). At the lesion level, the results of each consolidated summary were as follows: sensitivity of 0.40 (95% CI 0.21-0.62), specificity of 0.99 (95% CI 0.95-1.00), PLR of 40.0 (95% CI 9.1-176.3), NLR of 0.61 (95% CI 0.42-0.87), DOR of 66 (95% CI 14-311), and AUC of 0.86 (95% CI 0.83-0.89).Conclusions::18F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk PCa. The diagnostic efficacy was almost equivalent to that reported for 68Ga-PSMA PET/CT. Registration::International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023391101.

Objective:To explore the predictive value of the systemic immune inflammation index (SII) for the risk of bone metastases in patients with newly diagnosed prostate cancer (PCa).Methods:From Jun. 2012 to Jul. 2019, the clinical features of 308 patients were retrospectively analyzed. For the baseline clinical data of the patients with newly diagnosed PCa, the median age was 71(65-76) years, there were 59(19.2%) patients with a positive digital rectal examination (DRE). In addition, the median serum total prostate-specific antigen (tPSA), prostate volume (PV) and prostate-specific antigen density(PSAD)were 60.55(23.55-100.00) ng/ml, 39.35(28.29-56.66)ml and 1.27(0.58-2.52)ng/(ml·cm 3), respectively. There were 33(10.7%)patients with prostate biopsy Gleason score≤6, 115(37.3%)patients with a Gleason score=7 and 160(52.0%)patients with a Gleason score≥8. The T clinical stage also obtained, including 21(6.8%)diagnosed as T 1 stage, 87(28.2%)T 2 stage, 65(21.1%)T 3stage, 135(43.9%)T 4 stage. SII was calculated by the formula platelet×neutrophil/lymphocyte, and the median(interquartile range)of SII was 458.60(300.42-727.11)/L. According to the results of bone scanning, the patients were divided into bone metastasis(146, 47.4%)and a non-bone metastasis groups(162, 52.6%). The differences in the baseline clinical characteristics between the two groups were analyzed. The risk factors of bone metastasis were analyzed by univariate and multivariate logistic regression analysis. The diagnostic efficiency of the risk factors were evaluated by receiver operating characteristic(ROC)curve. Results:The median(interquartile range)of SII was 564.78/L(333.85-961.93/L)in patients with bone metastasis which were higher than those without bone metastasis 413.01(267.63-601.79)/L( P<0.001). The median(interquartile range)of tPSA were 97.79(48.20-119.10)ng/ml in bone metastasis group and 32.56(17.89-72.70)ng/ml in non-bone metastasis group ( P<0.001). The median(interquartile range)of PSAD were 1.91(0.97-3.55)ng/(ml·cm 3)and 0.90(0.45-1.77)ng/(ml·cm 3)in these two groups( P<0.001), respectively. In bone metastasis group, there were 132(90.4%)patients with a positive DRE, yet there were only 117(72.2%) patients with a positive DRE in the other group ( P<0.001). There were 7(4.8%)patients with prostate biopsy Gleason score≤6, 50(34.2%)patients with a Gleason score=7 and 89(61.0%)patients with a Gleason score≥8 in bone metastasis group. There were 26(16.1%)patients with prostate biopsy Gleason score≤6, 65(40.1%)patients with a Gleason score=7 and 71(43.8%)patients with a Gleason score≥8 in non-bone metastasis group ( P<0.001). There were statistically significant difference between the two groups in T clinical stage( P<0.001). In bone metastasis group, there were 2(1.4%)T 1 stage, and 19(13.0%)T 2 stage, 25(17.1%)T 3stage, and 100(68.5%)T 4 stage. Comparatively, there were 19(11.7%)T 1 stage, 68(42.0%)T 2 stage, 40(24.7%)T 3stage, and 35(21.6%)T 4 stage in the other group. There were no statistically significant difference between the two groups in term of age( P=0.057) and TPV( P=0.222). Univariate and multivariate logistic regression analysis showed that tPSA( P=0.003), SII( P<0.001), T clinical stage( P<0.001)could be regarded as independent risk factors of bone metastasis of PCa. Area under the curve of SII+ tPSA was 0.770, which was higher than SII(0.653)or tPSA(0.729) alone( P<0.05). When the cut-off value was 727.72/L, the sensitivity and specificity of the diagnosis of SII alone were 38.4% and 87.7%. The sensitivity and specificity of tPSA alone were 67.1%and 75.9% when the cut-off value was 73.02ng/ml. The sensitivity was 72.6% and the specificity was 71.6% when SII and tPSA was combined. Conclusions:SII is an independent predictor of bone metastasis of newly diagnosed with PCa. , and the patients were at high risk when SII exceeded 727.72/L. The combination of SII and tPSA can improve its predictive validity for the risk of bone metastasis.

Objective:To investigate the risk factors for Gleason score upgrading after radical prostatectomy in clinical low-risk prostate cancer patients aged≥65 years.Methods:A total of 485 clinical low-risk prostate cancer patients aged≥65 years at five centers of the national multi-center PC-follow database from January 2015 to March 2019 were retrospectively analyzed.Data including age at diagnosis, prostate-specific antigen(PSA), MRI prostate imaging, puncture Gleason score, operation method, puncture method, positive incision margin and capsule penetration were collected.Differences in Gleason scores before and after operation were compared, and the risk factors for Gleason score upgrading after radical resection were evaluated by univariate and multivariate Logistic regression analysis.Results:Of 485 patients with a puncture Gleason score of 3+ 3=6, 261(53.8%)cases had postoperative pathological upgrading, in whom 228(87.4%)cases had Gleason score upgrading of 7, 22(8.4%)had Gleason score upgrading of 8, and 11(4.2%)had Gleason score upgrading of 9 or more.The rate of Gleason score upgrading was elevated with increased preoperative PSA levels, positive pelvic MRI, and higher positive rates of puncture biopsy.The incidences of postoperative capsule penetration(27.2% vs.12.5%, P<0.001)and positive incision margin(25.2% vs.17.4%, P=0.036)had statistically significant differences between the pathologically upgraded group and the pathologically non-upgraded group.Multivariate analysis showed that preoperative PSA level, percentage of positive puncture biopsies, biopsy Gleason score and pelvic MRI were independent predictors of prostate cancer. Conclusions:For clinical low-risk prostate cancer patients aged≥65 years with high risk factors for Gleason score upgrading, repeated biopsies should be carried out when necessary and the treatment plan should be adjusted accordingly.

Objective:To establish a nomogram model for predicting positive resection margins after prostate cancer surgery, and to perform the corresponding verification, in order to predict the risk of positive resection margins after surgery.Methods:A total of 2 215 prostate cancer patients from The First Affiliated Hospital of Naval Medical University, Hospital, Peking University First Hospital, Peking University Third Hospital, Peking University, and First Affiliated Hospital of Xi′an Jiaotong University were included in the PC-follow database from 2015 to 2018, and a simple random sampling method was used. They were divided into 1 770 patients in the modeling group and 445 patients in the verification group. In the modeling group, the age (<60 years, 60 to 70 years, >70 years), PSA (<4 ng/ml, 4-10 ng/ml, 11-20 ng/ml, >20 ng/ml), pelvic MRI (negative, suspicious, positive), clinical stage of the tumor (T 1-T 2, ≥T 3), percentage of positive needles (≤33%, 34%-66%, >66%), Gleason score of biopsy pathology (≤6 points, 7 points, ≥8 points). Univariate and multivariate logistic analysis were performed to screen meaningful indicators to construct a nomogram model. The model was used for validation in the validation group. Results:The results of multivariate analysis showed that preoperative PSA level ( OR=2.046, 95% CI 1.022 to 4.251, P=0.009), percentage of puncture positive needles ( OR=1.502, 95% CI 1.136 to 1.978, P=0.002), Gleason score of puncture pathology ( OR=1.568, 95% CI 1.063 to 2.313, P=0.028), pelvic MRI were correlated ( OR=1.525, 95% CI 1.160 to 2.005, P=0.033). Establish a nomogram model for independent predictors of positive margin of prostate cancer. The area under the receiver operating characteristic (ROC) curve of the validation group is 0.776. The area under the ROC curve of the preoperative PSA level, percentage of puncture positive needles, puncture pathology Gleason score, pelvic MRI, postoperative pathology Gleason score were 0.554, 0.615, 0.556, 0.522, and 0.560, respectively. The difference between the nomogram model and other indicators was statistically significant ( P<0.05). Conclusions:The constructed nomogram model has higher diagnostic value than the preoperative PSA level, percentage of puncture positive needles, Gleason score of puncturing pathology, pelvic MRI, and postoperative pathological Gleason score in predicting positive margin.

Objective To translate the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) and ICIQ-MLUTS long form (ICIQ-MLUTS LF) into Chinese and assess their metric properties and applicability.Methods After obtaining permission from the International Consultation on Incontinence Questionnaire (ICIQ),original ICIQ-MLUTS and ICIQ-MLUTS LF were translated into Chinese according to ICIQ validation protocol and cultural adaptation guideline.During November 2017 to August 2018,Chinese version of ICIQ-MLUTS and ICIQ-MLUTS LF were tested by administering them in 6 and 12 hospitals in China respectively.To validate the translated questionnaires,the following tests were undertaken.The content validity was determined by indepth interviews with participants and experts.The correlation coefficients of ICIQ-MLUTS and ICIQ-MLUTS LF with International Prostate Symptom Score (IPSS) were assessed to validate criterion validity.Cronbach's alpha test was used to explore internal consistency.And the test-retest reliability was evaluated by calculation of intraclass correlation coefficient.Results In total,Chinese ICIQ-MLUTS and ICIQ-MLUTS LF were administrated to 135 and 230 male patients with lower urinary tract symptoms respectively.Both questionnaires had good content validity and good criterion validity with IPSS (Pearson correlation 0.846 and 0.833 for ICIQ-MLUTS and ICIQ-MLUTS LF respectively,both P ＜ 0.001).The Cronbach's alpha coefficient was 0.797 for ICIQ-MLUTS,and 0.853 for ICIQ-MLUTS LF.Intraclass correlation coefficient was 0.986 and 0.985 respectively (both P ＜ 0.001),showing good test-retest reliability.Conclusions The Chinese version of ICIQ-MLUTS and ICIQ-MLUTS LF had good validity and reliability,which can be used to assess Chinese male patients with lower urinary tract symptoms.

Objective To investigate the correlations of serum prealbumin and albumin with the shortterm outcome in patients with acute cerebral infarction in different age groups.Methods Patients with acute ischemic stroke admitted to hospital with 48 h were prospectively enrolled in the study.The modified Rankin Scale was used to assess the functional outcomes at 14 d after onset,0-2 was defined as a good outcome.According to the age of the patients,they were divided into either a young and middle-aged group (＜ 60 years) or an elderly group (≥60 years).The demography,baseline clinical data and laboratory findings of the patients were compared in the overall patients and the different age groups between the good outcome group and the poor outcome group.Multivariate logistic regression analysis was used to determine the independent influencing factors of short-term outcomes.Results A total of 622 patients with acute ischemic stroke were enrolled,including 402 (64.6％) males and 220 (35.4％) females;206 (33.1％) were in the young and middle-aged group,and 416 (66.9％) were in the elderly group;310 (49.8％) had good outcomes and 312 (50.2％) had poor outcomes.There were significant differences in the proportions of patients in male,old people,hyperlipidemia,diabetes mellitus,history of previous stroke or transient ischemic attack (TIA),as well as age,body mass index,levels of prealbumin,albumin,triglyceride,high-density lipoprotein cholesterol low-density lipoprotein cholesterol total bilirubin,direct bilirubin,indirect bilirubin,urea nitrogen,and uric acid between the good outcome group and the poor outcome group (all P ＜0.05).Multivariate logistic regression analysis showed that the female (odds ratio [OR] 1.522,95％ confidence interval [CI] 1.023-2.266;P =0.038),diabetes (OR 1.789,95％ CI 1.171-2.735;P =0.007) and higher low-density lipoprotein cholesterol (OR 1.251,95％ CI 1.017-1.539;P =0.034),total bilirubin (OR 1.054,95％ CI 1.029-1.081;P＜0.001),urea nitrogen (OR 1.245,95％ CI 1.100-1.409;P=0.001),and baseline National Institutes of Health Stroke Scale (NIHSS) score (OR 2.854,95％ CI 1.027-3.628;P =0.019) were the independent risk factors for poor outcomes,and higher prealbumin (OR 0.798 95％ CI 0.633-0.979;P =0.034) and albumin (OR 0.741,95％ CI 0.693-0.988;P =0.020) were the independent predictors of good outcomes.In the young and middle-aged patients,there were significant differences in the proportions of patients with small artery occlusion as well as age,triglyceride,and high-density lipoprotein cholesterol levels between the good outcome group and the poor outcome group (all P ＜0.05);multivariate logistic regression analysis showed that diabetes (OR 2.343 95％ CI 1.127-4.871;P=0.023) and higher baseline NIHSS scores (OR 2.041,95％ CI 1.304-4.125;P =0.027) were the independent risk factors for poor outcome,and higher high-density lipoprotein cholesterol (OR 0.742 95％ CI 0.639-0.937;P =0.044)was an independent predictor for good outcome.In the elderly patients,there were significant differences in the proportions of patients in male,previous stroke or TIA,and cardiogenic embolism,as well as prealbumin,low-density lipoprotein cholesterol,total bilirubin,direct bilirubin,indirect bilirubin,and uric acid levels between the good outcome group and the poor outcome group (all P ＜ 0.05);multivariate logistic regression the analysis showed that diabetes (OR 2.797,95％ CI 1.153-4.756;P =0.039),higher baseline NIHSS score (OR 2.586,95％ CI 1.033-3.435;P =0.035) and higher low-density lipoprotein cholesterol (OR 1.304,95％ CI 1.027-1.656;P =0.029) were the independent risk factors for poor outcome,and higher prealbumin was an independent predictor for good outcome (OR 0.795,95％ CI 0.691-0.998;P =0.002).Conclusions Prealbumin and albumin are the independent predictors for short-term good outcome in patients with acute ischemic stroke.The protective effect of serum prealbumin is more obvious in the elderly population (≥60 years).

Objective: To investigate the effect of the gene interfering technology on fatty acid synthase (FAS) gene silencing for lipid contents in human hepatic cell line HepG2 and to study the lipid metabolism related gene expression in HepG2 cells. Methods: A total of 3 pairs of small interfering RNA (siRNA) targeting different sequences of FAS mRNA were synthesized as FAS-siRNA-1, FAS-siRNA-2 and FAS-siRNA-3, meanwhile, 2 controls were established as Blank control group, in which HepG2 cells were not treated, and Negative control group, in which HepG2 cells were transfected by non-effective siRNA. The mRNA, and protein expression levels of FAS in HepG2 cells were examined by real-time lfuorescence quantitative RCR and Western blot analysis to screen the most effective pair of siRNA for FAS gene silencing; and that speciifc siRNA was transtected to HepG2 cells for 48 hours to detect the intra-/extra-cellular TG, TC levels and the mRNA expression related to lipid metabolism in HepG2 cells. Results: The screening experiment indicated that FAS-siRNA-3 was most effective for FAS gene silencing. Compared with Blank control group, the mRNA and protein expressions in FAS-siRNA-3 transfected HepG2 cells (Transfected group)decreased to (52.33 ± 3.07) % and (51.57 ± 3.14) % respectively. Compared with Blank control group, Transfected group had the reduced intra-/extra-cellular TG levels and reduced extracellular TC level; while increased mRNA expression of hepatic lipase,P<0.0001 and decreased mRNA expression of TG transfer protein in HepG2 microsome,P<0.05. Conclusion: FAS gene silencing could signiifcantly decrease the intra-/extra- cellular TG level and extracellular TC level in HepG2 cells, those ifndings need to be conifrmed by furtherin vivo andin vitro studies.

BACKGROUNDOveractive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB.

METHODSThis was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated.

RESULTSAt baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy.

CONCLUSIONSWe showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Prospective Studies ; Quality of Life ; Quinuclidines ; therapeutic use ; Solifenacin Succinate ; Tetrahydroisoquinolines ; therapeutic use ; Treatment Outcome ; Urinary Bladder, Overactive ; drug therapy

Objective To investigate the relationship of lower urinary tract symptoms (LUTS)with ageing in elderly population of Beijing. Methods From January 2010 to July 2010, the males over 40 years of age, who came to take routine health examination in Beijing Hospital, received a questionnaire related to urinary symptoms. Eligible men were classified into age groups spanning 10 years, and the urinary symptoms of each group were analyzed. Results Among the 2357 males who were investigated, the incidence of urinary symptoms increased, and the satisfaction of urinate decreased with ageing. In 40-49 age group, 44.94 % of males owned at least one urinary symptom and 71.47% of males were satisfied with their symptoms. In over-80 age group, these figures were 94.97% and 27.67%, respectively. Each symptom was associated with the satisfaction. Nocturia was the commonest symptom in each age group. Conclusions LUTS are common in elderly males and the incidence increases with ageing. Nocturia is the commonest symptom in elderly males.