Urinary incontinence rehabilitation of after radical prostatectomy: a systematic review and network meta-analysis.

Purpose: The aim of this study is to provide treatment for patients with urinary incontinence at different periods after radical prostatectomy. Methods: The PubMed, Embase, Cochrane, and Web of Science were searched for all literature on the effectiveness on urinary control after radical prostate cancer between the date of database creation and 15 November 2023 and performed a quality assessment. A network meta-analysis was performed using RevMan 5.3 and Stata 17.0 software and evaluated using the surface under the cumulative ranking curve. Results: The results of the network meta-analysis showed that pelvic floor muscle therapy including biofeedback with professional therapist-guided treatment demonstrated better results at 1 month to 6 months; electrical stimulation, biofeedback, and professional therapist guidance may be more effective at 3 months of treatment; professional therapist-guided recovery may be less effective at 6 months of treatment; and combined therapy demonstrated better results at 1 year of treatment. During the course of treatment, biofeedback with professional therapist-guided treatment may have significant therapeutic effects in the short term after surgery, but, in the long term, the combination of multiple treatments (pelvic floor muscle training+ routine care + biofeedback + professional therapist-guided treatment + electrical nerve stimulation therapy) may address cases of urinary incontinence that remain unrecovered long after surgery. Conclusion: In general, all treatment methods improve the different stages of functional recovery of the pelvic floor muscles. However, in the long term, there are no significant differences between the treatments. Given the cost-effectiveness, pelvic floor muscle training + routine care + biofeedback + professional therapist-guided treatment + electrical nerve stimulation therapy within 3 months and pelvic floor muscle + routine care after 3 months may be a more economical option to treat urinary incontinence. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=331797, identifier CRD42022331797.

Fighting against drug-resistant tumors by the inhibition of γ-glutamyl transferase with supramolecular platinum prodrug nano-assemblies.

Pt(ii)-based antitumor drugs (e.g. cisplatin and oxaliplatin) are one of the most successful and frequently used drugs in cancer chemotherapy at present. However, drug resistance and severe side effects are the major problems in the application of platinum drugs. Detoxification of Pt(ii) drugs is one of the most important mechanisms of drug resistance. Herein, a supramolecular Pt(iv) prodrug nano-assembly delivery system is designed and used to encapsulate a γ-glutamyl transferase (GGT) inhibitor (OU749) (Pt-CD/Dex-Ad@OU nano-assemblies) for the synergistic chemotherapy of cisplatin-resistant cancer. Pt-CD/Dex-Ad@OU nano-assemblies could be efficiently taken up by cisplatin-resistant cancer cells and release a drug in the intracellular reductive environment. The Pt-CD/Dex-Ad@OU nano-assemblies can efficiently suppress the expression of GGT, depleting GSH and augmenting ROS via the reduction of the Pt(iv) prodrug. Thereby, by breaking the redox balance the detoxification and antiapoptosis mechanisms of Pt(ii) drugs can be overcome. Thereafter, the excellent therapeutic efficacy of Pt-CD/Dex-Ad@OU nano-assemblies is validated on a cisplatin-resistant human non-small cell lung cancer (A549/DDP) model. Furthermore, the inhibition of GGT protein is expected to reduce the nephrotoxicity of cisplatin. Collectively, this study provides a promising strategy to break the redox balance for overcoming drug resistance and maximizing the efficacy of platinum-based cancer therapy.

Pre-surgery beliefs about pain and surgery as predictors of acute and chronic post-surgical pain: A prospective cohort study.

BACKGROUND: Chronic pain post-surgical pain (CPSP) is common and has far-reaching negative consequences for patients, yet relatively few studies have evaluated the impact of both deficit- and resource-based beliefs about pain and surgery on subjective intensities of acute and chronic post-surgical pain. To address this issue a prospective cohort study was performed. METHOD: 259 consecutive surgery patients from general surgery, gynecology, and thoracic departments completed a self-report battery of demographics, pain experiences, and psychological factors 24 h before surgery (T1) and provided follow-up pain intensity ratings 48 h-72 h after surgery (T2), and at a 4-month follow-up (T3). RESULTS: In the hierarchical regression model for acute post-operative pain intensity, pre-surgery pain self-efficacy beliefs made a significant unique contribution independent of all other pre-surgery and surgery-related factors (i.e., age, presence of pre-surgical pain, type of anesthesia, surgery duration). In the prediction model for intensity of chronic post-surgical pain, beliefs about long-term effects of surgery had a unique impact after controlling other significant pre-surgery and surgery influences (gender, education, surgery time). CONCLUSION: Results underscored the potential utility of considering specific pre-surgery pain- and surgery-related beliefs as factors that predict patient experiences of acute and chronic post-operative pain.

Identifying At-Risk Subgroups for Acute Postsurgical Pain: A Classification Tree Analysis.

Objective: Acute postsurgical pain is common and has potentially negative long-term consequences for patients. In this study, we evaluated effects of presurgery sociodemographics, pain experiences, psychological influences, and surgery-related variables on acute postsurgical pain using logistic regression vs classification tree analysis (CTA). Design: The study design was prospective. Setting: This study was carried out at Chongqing No. 9 hospital, Chongqing, China. Subjects: Patients (175 women, 84 men) completed a self-report battery 24 hours before surgery (T1) and pain intensity ratings 48-72 hours after surgery (T2). Results: An initial logistic regression analysis identified pain self-efficacy as the only presurgery predictor of postoperative pain intensity. Subsequently, a classification tree analysis (CTA) indicated that lower vs higher acute postoperative pain intensity levels were predicted not only by pain self-efficacy but also by its interaction with disease onset, pain catastrophizing, and body mass index. CTA results were replicated within a revised logistic regression model. Conclusions: Together, these findings underscored the potential utility of CTA as a means of identifying patient subgroups with higher and lower risk for severe acute postoperative pain based on interacting characteristics.

Protein kinase B and extracellular signal-regulated kinase contribute to the chondroprotective effect of morroniside on osteoarthritis chondrocytes.

Despite extensive studies on the multifaceted roles of morroniside, the main active constituent of iridoid glycoside from Corni Fructus, the effect of morroniside on osteoarthritis (OA) chondrocytes remains poorly understood. Here, we investigated the influence of morroniside on cultured human OA chondrocytes and a rat experimental model of OA. The results showed that morroniside enhanced the cell viability and the levels of proliferating cell nuclear antigen expression (PCNA), type II collagen and aggrecan in human OA chondrocytes, indicating that morroniside promoted chondrocyte survival and matrix synthesis. Furthermore, different doses of morroniside activated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in human OA chondrocytes, and in turn, triggered AKT/S6 and ERK/P70S6K/S6 pathway, respectively. The PI3K/AKT inhibitor LY294002 or the MEK/ERK inhibitor U0126 attenuated the effect of morroniside on human OA chondrocytes, indicating that the activation of AKT and ERK contributed to the regulation of morroniside in human OA chondrocytes. In addition, the intra-articular injection of morroniside elevated the level of proteoglycans in cartilage matrix and the thickness of articular cartilage in a rat experimental model of OA, with the increase of AKT and ERK activation. As a consequence, morroniside has chondroprotective effect on OA chondrocytes, and may have the therapeutic potential for OA treatment.

A small peptide derived from p53 linker region can resume the apoptotic activity of p53 by sequestering iASPP with p53.

One of the most important tumor suppression functions of p53 is its ability to induce apoptosis. iASPP is an inhibitory member of the ASPP protein family. It can specifically inhibit the normal function of p53 as a suppressor. The mechanism of iASPP suppressing the cell apoptotosis is through inhibiting the transactivation function of p53 on the promoters of proapoptotic genes by binding with p53. Therefore, relieving the combination of iASPP with p53 and leaving p53 free may be a useful strategy to activate p53 function. We therefore use A34, a small peptide derived from p53 linker region, to investigate the possibility of resuming the apoptosis activity of p53 by sequestering iASPP with p53 and derepressing p53. The results show that A34 can competitively combine with iASPP and therefore release p53 from iASPP; A34 can enhance the transcriptional activity of p53 on the promoters of Bax and PUMA; A34 can increase cell apoptosis and slow tumor growth in vitro and vivo. This study will open the way for using small molecule peptides that directly disturb the interaction of p53 with iASPP, thereby resume function of p53 as a suppressor.

iASPP inhibits p53-independent apoptosis by inhibiting transcriptional activity of p63/p73 on promoters of proapoptotic genes.

The ability to induce apoptosis is the most important tumor-suppression function of p53. Inhibitory member of apoptosis-stimulating protein of p53 family (iASPP) is an apoptotic-specific regulator of p53. iASPP suppresses apoptosis by inhibiting the transactivation function of p53 on the promoters of proapoptotic genes; however, the mechanism whereby iASPP influences apoptosis in tumor cells with mutant or deficient p53 has not been completely defined. In this study, we investigated the role of iASPP in the p63/p73 apoptosis pathway. iASPP inhibited apoptosis independently of p53 in tumor cells, mainly by inhibiting the transcriptional activity of p63/p73 on the promoters of proapoptotic genes. Because p63 and p73 are rarely mutated in human cancers, inhibiting the expression of endogenous iASPP may provide a useful strategy for restoring the apoptotic activity of p63 and p73 in human tumors with p53 loss or mutation. These results represent a promising new strategy for the treatment of cancers with non-wild-type p53.

Construction of a full-length iASPP expression plasmid pcDNA3.1+/iASPP and its biological activity.

In order to obtain a full-length expression plasmid for the p53 inhibitor protein, iASPP, fractional amplification was used to clone its full-length coding sequence (CDS) region. The amplified PCR product was then digested and inserted into the pMD19-T simple vector and subcloned into the pCDNA3.1(+) vector. A recombinant eukaryotic expression vector containing the complete CDS region of iASPP was successfully constructed. pcDNA3.1(+)/iASPP was able to express iASPP protein in an in vitro translation system and in cells. Its biological activity was verified using Western blotting, immunoprecipitation and cell apoptosis analysis. This successful preparation of a full-length iASPP expression plasmid lays the foundations for further studies on the function of iASPP.

Androgen receptor CpG island methylation status in human leukemia cancer cells.

The methylation status of the androgen receptor gene (AR) in leukemia cell lines was investigated. Results showed the presence of both methylated and unmethylated CpG islands of the AR promotor in leukemia cell lines. In the normal blood samples, only unmethylated bands were observed. In 15 bone marrow samples from patients with leukemia, 12 cases (80%) showed both methylated and unmethylated alleles and 3 cases (20%) showed only methylated alleles. To understand whether AR mRNA and protein expression are reduced by methylation, we treated leukemia cells with 5-Aza-Dc and detected the expression of mRNA and protein by RT-PCR and immunohistochemistry. The treatment of 5-Aza-Dc increased AR expression in all cell lines researched. This study indicates that reduced AR mRNA expression in leukemia cell lines was in part related to DNA methylation. The aberrant methylation of AR gene could be one molecular and genetic alteration in leukemia.

Effect of RNA interference of iASPP on the apoptosis in MCF-7 breast cancer cells.

ASPP family is proved to be apoptotic specific regulators of p53. Among them, iASPP acts as an inhibitor of p53. To investigate the effect of the iASPP RNAi on the apoptosis of breast cancer cell MCF-7, we transfected the recombinant plasmid PGCsilencer H1/Neo/GFP/RNAi into MCF-7. The iASPP expression was analyzed by RT-PCR and Western blot. The cell apoptosis was detected by FCM. The results show that the expression of iASPP is descended and the apoptosis rate is increased after transfection. Therefore, we conclude that inhibition of expression of iASPP may resume the ability of p53 to induce apoptosis in MCF-7 cells.

Prevalence and factors associated with CKD: a population study from Beijing.

BACKGROUND: Chronic kidney disease (CKD) is considered a serious worldwide public health problem, but data from developing countries are extremely limited. STUDY DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A representative sample of 13,925 adults in Beijing, China. PREDICTORS: Age (18 to 39, 40 to 59, 60 to 69, and >70 years), sex, urban or rural area, history of chronic respiratory infection and cardiovascular disease, hepatitis B virus infection, smoking, family history (diabetes, hypertension, and CKD), nephrotoxic medications, central obesity, diabetic and hypertension status, and dyslipidemia. OUTCOMES AND MEASUREMENTS: CKD was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) or markers of kidney damage. Glomerular filtration rate was estimated by using calibrated serum creatinine level and a formula specific for China. Persistent albuminuria and hematuria were considered markers of kidney damage. RESULTS: The prevalence of CKD in adults in Beijing was 13.0% (95% confidence interval [CI], 11.9 to 14.2). It therefore was estimated that the number of adults in Beijing with CKD was 1.43 million. In subjects aged 18 to 39, 40 to 59, 60 to 69, and older than 70 years, prevalences of CKD were 10.0% (95% CI, 8.9 to 11.3), 14.2% (95% CI, 13.0 to 15.4), 20.8% (95% CI, 18.1 to 23.9), and 30.5% (95% CI, 26.6 to 34.7), respectively. Factors independently associated with decreased kidney function included older age (odds ratio [OR], 1.83; 95% CI, 1.51 to 2.22 per 10-year increase), nephrotoxic medications (OR, 2.19; 95% CI, 1.21 to 3.97), rural area (versus urban area; OR, 0.47; 95% CI, 0.28 to 0.78), history of cardiovascular disease (OR, 2.04; 95% CI, 1.24 to 3.38), high-density lipoprotein cholesterol level less than 40 mg/dL (OR, 3.00; 95% CI, 1.39 to 6.51), and hypertension status (with duration > 10 years; OR, 1.85; 95% CI, 1.19 to 2.88). LIMITATIONS: Kidney function and indicators of kidney damage were based on single measurements. CONCLUSIONS: CKD is a public health burden in Beijing.

Analysis of hTERT expression in exfoliated cells from patients with bladder transitional cell carcinomas using SYBR green real-time fluorescence quantitative PCR.

AIMS: To investigate whether hTERT mRNA expression could be used as a diagnostic and prognostic marker of bladder transitional cell carcinoma. METHODS: SYBR green I real-time fluorescence quantitative PCR method was used to quantify hTERT mRNA expression in exfoliated cells from patients with bladder transitional cell carcinomas. RESULTS: A significant correlation was observed between the level of hTERT mRNA expression in exfoliated cells collected in urine with pathological grade and clinical stage. CONCLUSIONS: Our results show that SYBR green real-time fluorescence quantitative evaluation of hTERT mRNA could be a useful marker of tumor progression for the early diagnosis and prognosis of bladder cancers.

[Study on chronic disease related behavior and lifestyle in adults in Beijing, 2005].

OBJECTIVE: To understand the distribution of chronic disease related behavior and lifestyle in adults from Beijing. METHODS: 16,658 adult residents from Beijing city were randomly selected with stratified multi-stage cluster sampling method in 2005. Each participant was invited to receive a set of standardized questionnaire, physical examinations and laboratory tests. RESULTS: In the adults living in Beijing, 33.2% were overweight and 16.4% were obesive. The current smoking rate was 26.2% and the regular smoking rate was 21.4%. 57.7% of the male and 4.6% of the female adults were current smokers. In male adults, 64.3% drank alcoholic beverage at least once per month while 16.1% drank almost everyday, 16.5% drank more alcohol than moderate, and 18.5% were binge drinkers. 46.0% of Beijing adults were in lack of active physical exercise. Unhealthy dietary habits such as:excess consumption of sodium or oil, lower intake of vegetable, milk and soybean productions, skipping breakfast, fond of salted vegetable and fried food intake, as well as eating snacks etc. were quite commonly seen in the adults from Beijing. In addition, most of the risk factors had a higher prevalence in the suburban areas and population at working-age. CONCLUSION: The prevalence rate of chronic risk factors was still high in adults of Beijing. Effective interventions should be carried out to prevent further worsening of the situation, especially in the suburban areas and people at working-age.

[Nutrition and health status of the Beijing residents].

OBJECTIVE: To investigate the constitution and health status of the Beijing residents, and the primary influencing factors on nutrition and health, as to finding out the epidemiological characters and the changing trend of chronic diseases and to establish scientific basis for the establishment of public health and disease prevention policies of Beijing. METHODS: A stratified multi-stage cluster randomly sampling method was used. In total, 18 districts were surveyed, and among them, 9 were conducted dietary survey. The investigation was based on household, and all family members were surveyed at their home. After having got the compliance from the family members, question asking, medical examination, laboratory test and dietary investigation were carried out in these people. RESULTS: The incidence rate of hypertension was 25.0% for the resident > or = 15 year-old, and over 50% for middle-aged and elderly people (> or = 45 years old). The incidence of diabetes for those not younger than 15 years old was 7.7%. The over-weight rate and the obesity rate for adults were 35.1% and 20.6%, respectively. CONCLUSION: The following risk factors of chronic disease, such as unreasonable diet pattern, deficient intake of some micronutrients, over-weight and obesity, lack of physical examination, smoking and over-drinking, should be the important factors influencing the health of Beijing residents severely.

ASPP--Apoptotic specific regulator of p53.

The p53 protein is one of the best-known tumor suppressors. The recently identified ASPP family (apoptosis-stimulating protein of p53) can interfere with the working of p53. Three members of ASPP family are proved to be apoptotic specific regulators of p53. The discovery of ASPP family may answer such questions as "how cells choose to die". Understanding the ASPP status in human cancer will allow us to develop better strategies to treat cancer.

Downregulated mRNA expression of ASPP and the hypermethylation of the 5'-untranslated region in cancer cell lines retaining wild-type p53.

The p53 protein is one of the best-known tumour suppressors. Recently discovered ASPP1 and ASPP2 are specific activators of p53. To understand, if apoptosis-stimulating protein of p53 (ASPP) inactivation offers a selective advantage to tumors that have wild-type p53, we measured the mRNA expression of ASPP1 and ASPP2 in tumor cell lines retaining wide-type p53. In addition, the CpG island methylation status of ASPP1 gene and ASPP2 gene in the 5'-untranslated region was also investigated in order to understand the possible cause of abnormal expression of ASPP1 and ASPP2 in the tumor cell lines retaining wide-type p53. The data showed that mRNA expression of ASPP1 and ASPP2 is downregulated and CpG island tested is hypermethylated. These results indicated that ASPP CpG island aberrant methylation could be one molecular and genetic alteration in wild-type p53 tumours.

Progesterone receptor gene inactivation and CpG island hypermethylation in human leukemia cancer cells.

Previous studies showed that progesterone receptor (PR), one of the hormone receptor superfamily, was only connected with the sex-correlated cancers such as breast cancer, endometrial cancer, prostate cancer, etc. This article deals with the PR gene in leukemia. We investigated the methylation status and the expression of the two different PR isoforms, PRA and PRB, in three leukemia cancer cell lines using methylation-specific polymerase chain reaction (MSP-PCR) and reverse transcription-PCR. The correlation of PR methylation and expression together with DNA methyltransferase (DNMT1) was further studied. We found that DNMT1 is required to maintain CpG methylation and aberrant gene silencing of PR gene in human leukemia cancer cells. The activity of 5-aza-2'-deoxycytidine in demethylation and gene reactivation may be through depleting cellular DNMT1 levels. In addition, extensive methylation of PRA and PRB was also observed in leukemia samples. Our results suggest that PR CpG island aberrant hypermethylation could be one molecular and genetic alteration in leukemia.

The multiple promoter methylation profile of PR gene and ERalpha gene in tumor cell lines.

The changes of methylation status of various gene promoters are a common feature of malignant cells and these changes can occur early in the progression process. Therefore, abnormal methylation can be used as cancer marker. Such studies will first require the development of a panel of methylated markers that are methylated in cancer tissues but unmethylated in normal tissues or methylated status is different between cancer tissues and normal tissues. By using methylation-specific PCR (MSP) assay method, we observed alterations in DNA methylation at the double promoter regions of the progesterone receptor (PR) gene and estrogen receptor (ERalpha) gene in various tumor cell lines. Compared with normal white blood cell, the methylation status of PRA promoter in various cancer cell lines changed from unmethylation pattern to methylation pattern. That of PRB promoter changed from both unmethylated and methylated alleles to only methylated allele. The methylation status of ERalpha-A and ERalpha-B promoter in various cancer cell lines are cell -specific. This study indicates that PR promoter methylation may be a molecular marker in various cancer detections. And the methylation status of ERalpha-A and ERalpha-B is cell-specific.