Changes in disease burden and global inequalities in bladder, kidney and prostate cancers from 1990 to 2019: a comparative analysis based on the global burden of disease study 2019.

BACKGROUND: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030. METHODS: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index. RESULTS: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019. CONCLUSIONS: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions.

Estimating disparities of prostate cancer burden and its attributable risk factors for males across the BRICS-plus, 1990-2019: A comparable study of key nations with emerging economies.

BACKGROUNDS: The study aimed to analyze epidemiology burden of male prostate cancer across the BRICS-plus, and identify potential risk factors by assessing the associations with age, period, birth cohorts and sociodemographic index (SDI). METHODS: Data were extracted from the Global Burden of Disease Study 2019. The average annual percent change (AAPC) was calculated to assess long-term trends, and age-period-cohort analysis was used to analyze these three effects on prostate cancer burden. Quantile regression was used to investigate the association between SDI and health outcomes. RESULTS: The higher incidence and mortality were observed in Mercosur and SACU regions, increasing trends were observed in prostate cancer incidence in almost all BRICS-plus countries (AAPC > 0), and EEU's grew by 24.31% (%AAPC range: -0.13-3.03). Mortality had increased in more than half of countries (AAPC > 0), and SACU grew by 1.82% (%AAPC range: 0.62-1.75). Incidence and mortality risk sharply increased with age across all BRICS-plus countries and globally, and the peak was reached in the age group 80-84 years. Rate ratio (RR) of incidence increased with birth cohorts in all BRICS-plus countries except for Kazakhstan where slightly decrease, while mortality RR decreased with birth cohort in most of BRICS-plus countries. SDI presented significantly positive associations with incidence in 50 percentiles. The deaths attributable to smoking declined in most of BRICS-plus nations, and many countries in China-ASEAN-FTA and EEU had higher values. CONCLUSION: Prostate cancer posed a serious public health challenge with an increasing burden among most of BRICS-plus countries. Age had significant effects on prostate cancer burden, and recent birth cohorts suffered from higher incidence risk. SDI presented a positive relationship with incidence, and the smoking-attributable burden was tremendous in China-ASEAN-FTA and EEU region. Secondary prevention should be prioritized in BRICS-plus nations, and health policies targeting important populations should be strengthened based on their characteristics and adaptability.

Construction of S-scheme CuInS2/ZnIn2S4 heterostructures for enhanced photocatalytic activity towards Cr(VI) removal and antibiotics degradation.

The efficient and ecofriendly removal of pharmaceutical antibiotics and heavy metal Cr(VI) from water sources is a crucial challenge in current environmental management. Photocatalysis presents a viable environmentally friendly solution for eliminating organic contaminants and heavy-metal ions. In this study, a novel S-scheme CuInS2/ZnIn2S4 (CIS/ZIS) heterojunction was developed using a one-pot solvothermal method. The optimized CIS/ZIS heterojunction exhibited considerably improved photocatalytic activity for the removal of antibiotics and Cr(VI), achieving over 90% removal for both tetracycline hydrochloride (TC) (20 mg/L) and Cr(VI) (20 mg/L) under visible light irradiation. The study also delved into the effect of coexisting inorganic anions and assessed the cyclic stability of the composite photocatalysts. This enhancement mechanism can be delineated into three key elements. First, the incorporation of the narrow-gap semiconductor CuInS2 effectively augmented the photoabsorption capacity. Second, the inclusion of ZnIn2S4 caused an increase in surface active sites. Most importantly, the internal electric field at the interface between CuInS2 and ZnIn2S4 expedited the separation of photogenerated carriers. Furthermore, the results revealed that superoxide radical and photogenerated holes are the primary active substance responsible for TC removal, while photogenerated electrons play a central role in the photoreduction of Cr(VI). To gain insights into the transport pathways of photogenerated carriers, we conducted experiments with nitrotetrazolium blue chloride (NBT) and photodeposited gold. This study offers an innovative approach to enhancing the photocatalytic performance of ternary In-based materials by constructing S-scheme heterojunctions.

Seawater Corrosion Resistance of Duplex Stainless Steel and the Axial Compressive Stiffness of Its Reinforced Concrete Columns.

In order to explore the corrosion resistance of duplex stainless steel under seawater corrosion and the compressive stiffness of its reinforced concrete columns, this study first performed seawater corrosion resistance tests on HRB400 ordinary steel rebar and S32205 duplex stainless steel rebar. The effect of the corrosion product film on the corrosion behavior was investigated through polarization curve tests and electrochemical impedance spectroscopy tests. The results showed that the corrosion rate of S32205 duplex stainless steel in a seawater environment was approximately 1/15 that of the HRB400 ordinary steel rebar. The anodic polarization curve of duplex stainless steel rebars exhibited a greater slope than that of carbon steel rebars. In the simulated seawater environment, the corrosion rate of these two kinds of steel bars showed different trends. The corrosion rate of ordinary steel bar HRB400 first decreased and then increased, while that of duplex stainless steel S2205 increased steadily. Furthermore, 18 short concrete columns reinforced with ordinary and duplex stainless steel rebars were subjected to the axial compression test and stiffness analysis; the stiffness of the short columns was calculated from the test data. The theoretical values agreed with the test values, with a stiffness calculation error of less than 5%.

Effects of three orthodontic retainers on periodontal pathogens and periodontal parameters.

The objective of this study was to compare and evaluate the changes in periodontal pathogens and periodontal status within 6 months of wearing three orthodontic retainers, namely, vacuum-formed retainer (VFR), Hawley retainer (HR), and lingual fixed retainer (LR). In total, 48 patients who underwent orthodontic treatment with ordinary metal brackets were divided into VFR, HR, and LR groups (n = 16 per group). Saliva samples were collected at the time of debonding (T0) and after 1 month (T1), 3 months (T2), and 6 months (T3). Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) were quantitatively analyzed using real-time PCR. Gingival index (GI), plaque index (PLI), and probing depth (PD) were measured at the four time points to evaluate changes in periodontal state. SPSS20.0 software was used to analyze the data, and P < 0.05 was considered statistically significant. The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2300073704), the registration was retrospective. Compared to baseline (T0) values, Pg, Aa, GI, PLI, and PD were significantly decreased in all three groups 1 month after wearing the retainer (p < 0.05). Significant differences were observed in Aa at T3 among the three groups, whereby the HR group exhibited significantly better results compared to the VFR and LR groups (p < 0.05). Differences were found among the three groups' Porphyromonas gingivalis at T3, and the HR group was significantly better than the VFR and LR groups (P < 0.05). From T1 to T2, GI, PLI, and PD of the three groups tended to be stable, however differences were observed at T3, with the PLI and PD of the HR group being the lowest among the three groups (p < 0.05). Regardless of the type of retainer used, the periodontal condition of patients was significantly improved after removal of the metal brackets. After 6 months of retainer use, the Hawley retainer was superior to vacuum-formed retainer and lingual fixed retainer with regard to Pg, Aa, and periodontal clinical parameters.

Stemness maintenance of stem cells derived from human exfoliated deciduous teeth (SHED) in 3D spheroid formation through the TGF-ß/Smad signaling pathway.

Mesenchymal stem cells (MSCs) have shown great potential as important therapeutic tools for dental pulp tissue engineering, with the maintenance and enhancement of their stemness being crucial for successful therapeutic application in vivo and three-dimensional (3D) spheroid formation considered a reliable technique for enhancing their pluripotency. Human exfoliated deciduous tooth stem cells (SHED) were cultured in a low attachment plate to form aggregates for five days. Then, the resulting spheroids were analyzed for pluripotent marker expression, paracrine secretory function, proliferation, signaling pathways involved, and distribution of key proteins within the spheroids. The results indicated that 3D spheroid formation significantly increased the activation of the transforming growth factor beta (TGF-ß)/Smad signaling pathway and upregulated the secretion and mRNA expression levels of TGF-ß, which in turn enhanced the expression of pluripotency markers in SHED spheroids. The activation of the TGF-ß/Smad signaling pathway through 3D spheroid formation was found to preserve the stemness properties of SHED. Thus, understanding the mechanisms behind pluripotency maintenance of SHED culture through 3D spheroid formation could have implications for the therapeutic application of MSCs in regenerative medicine and tissue engineering.

YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer.

Ferroptosis is a regulated cell death process initiated by iron-dependent phospholipid peroxidation and is mainly suppressed by GPX4-dependent and FSP1-dependent surveillance mechanisms. However, how the ferroptosis surveillance system is regulated during cancer development remains largely unknown. Here, we report that the YTHDC1-mediated m6A epigenetic regulation of FSP1 alleviates the FSP1-dependent ferroptosis suppression that partially contributes to the tumor suppressive role of YTHDC1 in lung cancer progression. YTHDC1 knockdown promoted the lung tumor progression and upregulated FSP1 protein level that resulted in ferroptosis resistance of lung cancer cells. Silencing FSP1 abrogated YTHDC1 knockdown-induced proliferation increase and ferroptosis resistance. Mechanistically, YTHDC1 binding to the m6A sites in the FSP1 3'-UTR recruited the alternative polyadenylation regulator CSTF3 to generate a less stable shorter 3'-UTR contained FSP1 mRNA, whereas YTHDC1 downregulation generated the longer 3'-UTR contained FSP1 mRNA that is stabilized by RNA binding protein HuR and thus led to the enhanced FSP1 protein level. Therefore, our findings identify YTHDC1 as a tumor progression suppressor in lung cancer and a ferroptosis regulator through modulating the FSP1 mRNA stability and thus suggest a ferroptosis-related therapeutic option for YTHDC1high lung cancer.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

The burden of chronic kidney disease associated with dietary exposure to cadmium in China, 2020.

Cadmium (Cd) exposure increases the risk of chronic kidney disease (CKD). But the contribution of dietary Cd intake, the primary exposure route of Cd in humans, to the CKD burden remains to be evaluated in China. Concentrations of Cd in foods and population glomerular filtration rate (GFR) were retrieved from studies published between January 2000 and February 2023 in China. Daily food consumption in adults aged ≥35 years old was obtained from two nationwide Chinese surveys. Dietary Cd intake and its contribution rate among total Cd exposure from diet, inhalation, smoking and water were evaluated. Urinary Cd (UCd) was estimated using the toxicokinetic (TK) model based on dietary Cd intake. The effect of Cd on kidney function has been quantified with the previously published dose-response relationship between UCd and GFR. The incidence and disability-adjusted life years (DALYs) of CKD attributable to dietary Cd intake were derived considering the contribution rate of dietary Cd intake at the national and provincial levels. The national average dietary Cd intake was 0.6891 µg/kg bw/day, contributing 63.69% of total Cd exposure. The Cd exposure through foods resulted in 2.34 (95% uncertainty interval, UI: 1.54-3.40) stage 4 CKD and 0.37 (95% UI: 0.20-0.59) stage 5 CKD cases per 100,000 persons/year in mainland China, 2020. The corresponding DALYs loss associated with stage 4 and stage 5 CKD due to dietary Cd intake were 5.14 (95% UI: 3.24-7.67) and 4.78 (95% UI: 2.32-8.30) per 100,000 persons/year, together accounting for 2% of total DALYs of CKD. Greater dietary Cd intake and corresponding burden of late-stage CKD were observed in Southern areas than in Northern areas. Diet remains the primary exposure to Cd in Chinese adults. Efforts to reduce dietary Cd exposure would positively impact public health, especially in Southern provinces with high Cd exposure.

Ten interleukins and risk of prostate cancer.

Background: Interleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them. Methods: We conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively. Results: The odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; P=1.58×10-05) and 1.12 (95% CI, 1.07, 1.17; P=6.61×10-07) for one standard deviation increase in genetically predicted IL-1ra and IL-6 levels, respectively. Genetically predicted levels of IL-1ß, IL-2a, IL-6ra, IL-8, IL-16, IL-17, IL-18, and IL-27 were not associated with the risk of prostate cancer. Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (ß, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (ß, 0.002; 95% CI, -0.011, 0.014; P=0.755). Conclusion: This MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.

A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1.

SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: The Novel Therapeutic Option for Regenerative Dentistry.

Dental mesenchymal stem cells (MSCs) are characterized by unlimited self-renewal ability and high multidirectional differentiation potential. Since dental MSCs can be easily isolated and exhibit a high capability to differentiate into odontogenic cells, they are considered as attractive therapeutic agents in regenerative dentistry. Recently, MSC-derived extracellular vesicles (MSC-EVs) have attracted widespread attention as carriers for cell-free therapy due to their potential functions. Many studies have shown that MSC-EVs can mediate microenvironment at tissue damage site, and coordinate the regeneration process. Additionally, MSC-EVs can mediate intercellular communication, thus affecting the phenotypes and functions of recipient cells. In this review, we mainly summarized the types of MSCs that could be potentially applied in regenerative dentistry, the possible molecular cargos of MSC-EVs, and the major effects of MSC-EVs on the therapeutic induction of osteogenic differentiation.

Secular trends of morbidity and mortality of prostate, bladder, and kidney cancers in China, 1990 to 2019 and their predictions to 2030.

BACKGROUND: Prostate, bladder and kidney cancers are common age-related genitourinary cancers. China's population is aging at an increasing rate, so predicting the morbidity and mortality of prostate, bladder, and kidney cancer in China is of great significance to provide epidemiological evidence for forward planning and implementation of national health policies. METHODS: Numbers of incidences and deaths by cancer (prostate, bladder and kidney), sex (male and female) and age groups from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study. We applied Bayesian age-period-cohort models to predict incidences and deaths to 2030. We also calculated Age-standardized incidence rate (ASIR) and mortality rate (ASMR), their trends were quantified by estimated average percentage change (EAPC) and 95% confidence interval (CI). RESULTS: Predictions suggest that by 2030, there will be 315,310 prostate cancer cases, 192,390 bladder cancer cases and 126,980 kidney cancer cases. The ASIRs will increase to 25.54/100,000 for prostate cancer (EAPC: 2.88, 95% CI, 2.84, 2.93), 7.54/100,000 for bladder cancer (EAPC: 2.58, 95% CI, 2.54, 2.61) and 5.63/100,000 for kidney cancer (EAPC: 4.78, 95% CI, 4.54, 5.02). Number of deaths in 2030 will be 81,540, 61,220, and 41,940, respectively. Different ASMR changes are observed, the ASMR for prostate cancer will drop to 7.69/100,000 (EAPC: -0.29, 95% CI, -0.31, -0.27), the ASMR for bladder cancer will stabilize at 2.49/100,000 (EAPC: 0.00, 95% CI, -0.02, 0.03), the ASMR of kidney cancer will increase to 1.84/100,000 (EAPC: 3.45, 95% CI, 3.22, 3.67). From 1990 to 2030, higher numbers of cases and rates are reported among males and in the 60 plus age group, both ASIR and ASMR of bladder and kidney cancers presents progressively widening differences between both males and females and between the < 60 and the ≥ 60 age groups. CONCLUSION: Morbidity and mortality of the three genitourinary cancers are predicted to increase further over the next decade. It highlights the need for timely development and implementation of optimal health policies to curb the epidemic trends.

Emerging photodynamic/sonodynamic therapies for urological cancers: progress and challenges.

Photodynamic therapy (PDT), and sonodynamic therapy (SDT) that developed from PDT, have been studied for decades to treat solid tumors. Compared with other deep tumors, the accessibility of urological tumors (e.g., bladder tumor and prostate tumor) makes them more suitable for PDT/SDT that requires exogenous stimulation. Due to the introduction of nanobiotechnology, emerging photo/sonosensitizers modified with different functional components and improved physicochemical properties have many outstanding advantages in cancer treatment compared with traditional photo/sonosensitizers, such as alleviating hypoxia to improve quantum yield, passive/active tumor targeting to increase drug accumulation, and combination with other therapeutic modalities (e.g., chemotherapy, immunotherapy and targeted therapy) to achieve synergistic therapy. As WST11 (TOOKAD® soluble) is currently clinically approved for the treatment of prostate cancer, emerging photo/sonosensitizers have great potential for clinical translation, which requires multidisciplinary participation and extensive clinical trials. Herein, the latest research advances of newly developed photo/sonosensitizers for the treatment of urological cancers, and the efficacy, as well as potential biological effects, are highlighted. In addition, the clinical status of PDT/SDT for urological cancers is presented, and the optimization of the photo/sonosensitizer development procedure for clinical translation is discussed.

Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.

BACKGROUND: Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. METHODS: We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis. RESULTS: The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI. CONCLUSION: This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

The causal association between smoking, alcohol consumption and risk of bladder cancer: A univariable and multivariable Mendelian randomization study.

Smoking and alcohol consumption are associated with bladder cancer risk in observational studies. We conducted a two-sample univariable and multivariable Mendelian randomization (MR) analysis to determine whether those associations are causal. We used 21, 126, 360, 39 single nucleotide polymorphisms (SNPs) as instrumental variables for number of cigarettes per day, lifetime smoking index, smoking initiation, and drinks per week, respectively. A total of 1115 cases with bladder cancer and 174 006 noncases from FinnGen consortium and 2883 cases with bladder cancer and 417 955 noncases from UK Biobank study were obtained. Genetic predisposition to cigarettes per day, lifetime smoking index and smoking initiation were positively associated with an increased risk of bladder cancer in both the FinnGen and UK Biobank consortium. The summary odds ratio (OR) of bladder cancer was 1.79 (95% confidence interval [CI], 1.31-2.45; P = .0002), 2.38 (95% CI, 1.45-3.88; P = .0005) and 1.91 (95% CI, 1.46-2.50; P = 1.59 × 10-06 ) for one SD increase in the number of cigarettes per day, lifetime smoking index and smoking initiation, respectively. The genetically instrumented number of drinks per week was not associated with bladder cancer (OR = 0.69; 95% CI, 0.44-1.10; P = .1237). Estimates were consistent in multivariable MR analyses by the adjustments of body mass index and education. Our study suggests a causal potential of the association of smoking but not alcohol consumption with bladder cancer according to current evidence.