Efficacy and safety of transurethral resection of bladder tumour combined with chemotherapy and immunotherapy in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer: a protocol for a randomized controlled trial.

BACKGROUND: Bladder cancer is the tenth most common cancer worldwide. For patients with T1 high-grade or T2 bladder cancer, radical cystectomy is recommended. However, radical cystectomy is associated with various complications and has a detrimental impact on the quality of life. Bladder-sparing therapy has been widely explored in patients with muscle-invasive bladder cancer, and whether a combination of transurethral resection of bladder tumour (TURBT) with chemotherapy and immunotherapy shows definite superiority over TURBT plus chemotherapy is still a matter of debate. The aim of this study is to investigate the efficacy and safety of TURBT combined with chemotherapy and immunotherapy in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer who are unwilling or unsuitable to undergo radical cystectomy. METHODS: An open-label, multi-institutional, two-armed randomized controlled study will be performed with 86 patients with T1 high-grade or T2 bladder cancer meeting the eligibility criteria. Participants in the experimental group (n = 43) will receive TURBT combined with chemotherapy (GC: gemcitabine 1000 mg/m2 on the 1st day and the 8th day, cisplatin 70 mg/m2 on the 2nd day, repeated every 21 days) and immunotherapy (toripalimab 240 mg on the 5th day, repeated every 21 days), and those in the control group (n = 43) will receive TURBT plus chemotherapy (GC). The primary outcome is pathological response, and the secondary outcomes include progression-free survival, overall survival, toxicities, and quality of life. DISCUSSION: To the best of our knowledge, this is the first study to evaluate the efficacy and safety of TURBT combined with GC regimen and toripalimab in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer. The expected benefit is that the combination of TURBT with chemotherapy and immunotherapy would be more effective than TURBT plus chemotherapy without compromising the quality of life and increasing the toxicity. TRIAL REGISTRATION: ChiCTR2200060546, chictr.org.cn, registered on June 14, 2022.

Association of cigarette smoking habits with the risk of prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Association of cigarette smoking habits with the risk of prostate cancer is still a matter of debate. This systematic review and meta-analysis aimed to assess the association between cigarette smoking and prostate cancer risk. METHODS: We conducted a systematic search on PubMed, Embase, Cochrane Library, and Web of Science without language or time restrictions on June 11, 2022. Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective cohort studies that assessed the association between cigarette smoking habits and the risk of prostate cancer were included. Quality assessment was conducted using the Newcastle-Ottawa Scale. We used random-effects models to obtain pooled estimates and the corresponding 95% confidence intervals. RESULTS: A total of 7296 publications were screened, of which 44 cohort studies were identified for qualitative analysis; 39 articles comprising 3 296 398 participants and 130 924 cases were selected for further meta-analysis. Current smoking had a significantly reduced risk of prostate cancer (RR, 0.74; 95% CI, 0.68-0.80; P < 0.001), especially in studies completed in the prostate-specific antigen screening era. Compared to former smokers, current smokers had a significant lower risk of PCa (RR, 0.70; 95% CI, 0.65-0.75; P < 0.001). Ever smoking showed no association with prostate cancer risk in overall analyses (RR, 0.96; 95% CI, 0.93-1.00; P = 0.074), but an increased risk of prostate cancer in the pre-prostate-specific antigen screening era (RR, 1.05; 95% CI, 1.00-1.10; P = 0.046) and a lower risk of prostate cancer in the prostate-specific antigen screening era (RR, 0.95; 95% CI, 0.91-0.99; P = 0.011) were observed. Former smoking did not show any association with the risk of prostate cancer. CONCLUSIONS: The findings suggest that the lower risk of prostate cancer in smokers can probably be attributed to their poor adherence to cancer screening and the occurrence of deadly smoking-related diseases, and we should take measures to help smokers to be more compliant with early cancer screening and to quit smoking. TRIAL REGISTRATION: This study was registered on PROSPERO (CRD42022326464).

Efficacy and safety of Androgen Deprivation Therapy (ADT) combined with modified docetaxel chemotherapy versus ADT combined with standard docetaxel chemotherapy in patients with metastatic castration-resistant prostate cancer: study protocol for a multicentre prospective randomized controlled trial.

BACKGROUND: Androgen deprivation therapy (ADT) combined with docetaxel chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (mCRPC) patients. However, mCRPC patients are mainly frail elderly men, constantly accompanied by comorbidities and showing poor tolerance to standard docetaxel chemotherapy. Some exploratory studies administering modified chemotherapy regimens have reported noninferior oncologic outcomes with fewer adverse events, yet most are retrospective or small studies, and prospective randomized controlled trials have rarely been conducted. Therefore, we designed this modified docetaxel chemotherapy regimen in patients with mCRPC, aiming to evaluate its efficacy and safety compared with the standard docetaxel chemotherapy regimen. METHODS: This is an open-label, multi-institutional, prospective, randomized non-inferiority trial. A total of 128 patients with mCRPC will be randomized to receive ADT combined with modified docetaxel chemotherapy (experimental group, n=64) or ADT combined with standard docetaxel chemotherapy (control group, n=64). Patients in the experimental group will receive a modified regimen with docetaxel 40 mg/m2 on the 1st day and 35 mg/m2 on the 8th day, repeated every 21 days. The primary endpoint is progression-free survival at 2 years. Secondary endpoints include overall survival, prostate-specific antigen response rate, pain response rate, toxicity and quality of life. DISCUSSION: The expected benefit for the patient in the experimental arm is noninferior efficacy with decreased toxicity and improved quality of life compared with that in the control arm. To the best of our knowledge, this will be the first multicentre prospective randomized study to assess the efficacy and safety of modified docetaxel chemotherapy in patients with mCRPC in China. The results of this trial may provide benefit to mCRPC patients, especially those with poor performance. TRIAL REGISTRATION: chictr.org.cn Identifier: ChiCTR2100046636 (May 24, 2021). Ongoing study.

Overexpression of PFKFB3 promotes cell glycolysis and proliferation in renal cell carcinoma.

BACKGROUND: Cancer cells prefer utilizing aerobic glycolysis in order to exacerbate tumor mass and maintain un-regulated proliferative rates. As a key glycolytic activator, phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) has been implicated in multiple tumor type progression. However, the specific function and clinical significance of PFKFB3 in renal cell carcinoma (RCC) are yet not clarified. This investigation assessed PFKFB3 roles in RCC. METHODS: PFKFB3 expression levels were analyzed in clear cell renal cell carcinoma (ccRCC) tissues, together with its relationship with clinical characteristics of ccRCC. Real-time PCR and Western blot assays were employed for determining PFKFB3 expression in different RCC cell lines. Furthermore, we determined the glycolytic activity by glucose uptake, lactate secretion assay and ECAR analysis. CCK-8 assay, clone formation, flow cytometry and EdU assessments were performed for monitoring tumor proliferative capacity and cell-cycle distribution. Furthermore, a murine xenograft model was employed for investigating the effect of PFKFB3 on tumor growth in vivo. RESULTS: PFKFB3 was significantly up-regulated in RCC specimens and cell lines in comparison to normal control. Overexpression of PFKFB3 was directly correlated to later TNM stages, thus becoming a robust prognostic biomarker for ccRCC cases. Furthermore, PFKFB3 knockdown suppressed cell glycolysis, proliferative rate and cell-cycle G1/S conversion in RCC cells. Importantly, in vivo experiments confirmed that PFKFB3 knockdown delayed tumor growth derived from the ACHN cell line. CONCLUSIONS: Such results suggest that PFKFB3 is a key molecular player in RCC progression via mediating glycolysis / proliferation and provides a potential therapeutic target against RCC.

Limnobacter parvus sp. nov., a Thiosulfate-Oxidizing Bacterium Isolated from Lake Water.

A novel bacterium, designated as strain YS8-69T, was isolated from an inland closed lake, Xinjiang Uygur Autonomous Region, PR China. Comparative analysis of the 16S rRNA gene sequence shows the strain was affiliated to the genus Limnobacter, in the family Burkholderiaceae, with the highest similarities to Limnobacter alexandrii LZ-4T (98.93%), Limnobacter thiooxidans DSM 13612T (98.55%), Limnobacter humi NBRC 111650T (97.66%), and Limnobacter litoralis KP1-19T (97.04%). Strain YS8-69T was a Gram stain-negative, strictly aerobic, rod shaped, catalase- and oxidase-positive bacterium, and growth was observed at 4-40 °C (optimum, 25 °C), pH 7.0-10.0 (optimum, pH 7.0), and 0-3% (w/v) NaCl (optimum, 0.5%). The principal fatty acids were C16:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The sole respiratory quinone was Q-8 and total polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), an unidentified aminolipid (AL), two unidentified glycolipids (GL1,2), an unidentified amino phosphoglycolipid (APGL), two unidentified phospholipids (PL1,2), two unidentified aminophospholipids (APL1,2), and three unidentified lipids (L1,2,3). The average nucleotide identity (ANI) values and in silico DDH between strain YS8-69T and L. alexandrii LZ-4T, L. thiooxidans JCM 13612T, and L. humi DSM 111650T were 73.0-80.6% and 15.8-50.2%, respectively. The genome sequence showed a length of 3,162,663 bp, with 20 contigs and 51.7% of G + C content. Based on physiological, chemotaxonomic, genotypic characteristics, and phylogenetic results, we propose that strain YS8-69T represents a novel specie of the genus Limnobacter, for which the name Limnobacter parvus sp. nov. is proposed (type strain YS8-69T = MCCC 1K08015T = KCTC 92278T).

Association between workplace bullying and nurses' professional quality of life: The mediating role of resilience.

AIM: We aim to determine workplace bullying in relation to the professional quality of life of nurses and the mediating role of resilience between workplace bullying and the professional quality of life. BACKGROUND: Workplace bullying is an increasingly serious problem worldwide and deleteriously affects the occupational health and quality of life of nurses. However, it has not attracted adequate managerial attention. METHOD: A cross-sectional study was conducted using a sample of 493 clinical nurses from two tertiary grade A hospitals in Guangzhou, China. Data were collected through an online questionnaire survey in July 2020 and analysed with structural equation modelling. RESULTS: Workplace bullying had negative and direct effects on the professional quality of life of nurses. Resilience mediated the relationship between workplace bullying and the professional quality of life. CONCLUSION: Resilience is a protective factor that helps nurses cope with workplace bullying. Managers can improve the professional quality of life of nurses by reducing workplace bullying and strengthening the resilience of nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Managers must take measures to prevent the workplace bullying of nurses. In addition, nurse supervisors should pay attention to the resilience of nurses and strengthen resilience training to help nurses withstand the pressure of workplace bullying and improve their professional quality of life.

Hsa_circ_0054633 association of C peptide is related to IL-17 and TNF-α in patients with diabetes mellitus receiving insulin treatment.

BACKGROUND: Chronic inflammation damaged the islet and resulted in dysfunction of T2D. Circular RNA is stable and better for biomarker in many diseases. Here, we aimed to identify potential circular RNA hsa_circ_0054633 that can be a biomarkers for the effects of insulin therapy in T2D. METHODS: In this retrospective case-control study, patients were from Li Huili Hospital, Ningbo, China, from February 10, 2019, to August 15, 2019. We included 47 healthy adults, 46 new-onset T2D with insulin resistance, and 51 patients with insulin therapy. Serum inflammation factors were tested by ELISA assays. We selected hsa_circ_0054633 as a candidate biomarker and measured its concentration in serum by qRT-PCR. The Pearson correlation test was used to evaluate the correlation between this circRNA and clinical variables. RESULTS: Clinical data indicated that serum C peptide was increased in T2D treatment with insulin. Serum hsa_circ_0054633 was decreased in insulin treatment group. Hsa_circ_0054633 was negative correlated with C peptide (r = -0.2841, p = 0.0433,). IL-1 and IL-6, IL-17, and TNF-α were higher in T2D patients and decreased after insulin treatment, only IL-17 and TNF-α showed a positive correlation to hsa_circ_0054633 (r = 0.4825, p < 0.0001, and r = 0.6190, p < 0.0001). The area under ROC curve was 0.7432, 0.5839, and 0.7573 for Hsa_circ_0054633, C peptide, and their combination. CONCLUSION: Hsa_circ_0054633 level was lower in T2D with insulin treatment than untreated and was a negative correlation with C peptide, and positively correlated with IL-17 and TNF-α, suggesting that hsa_circ_0054633 may be a potential early indicator of insulin treatment effect to improve inflammation condition.

Lower expression of Hsa_circRNA_102682 in diabetic hyperhomocysteinemia negatively related to creatinemia is associated with TGF-ß and CTGF.

BACKGROUND: Diabetic nephropathy is a kidney disease caused by long-term hyperglycemia. Hsa_circRNA_102682 is related to the pathogenesis of preeclampsia. Preeclampsia is related to hypertension and proteinuria, and diabetic nephropathy is mainly manifested by hypertension and proteinuria. The main pathological change in diabetic nephropathy is glomerular fibrosis. METHODS: This study used serum samples of patients treated at Li Huili Eastern Hospital, Ningbo, China, from July 10, 2018 to February 15, 2019. We included 73 patients with diabetes and divided them into a normal-homocysteine group and a high-homocysteine group. We selected used quantitative reverse transcriptase-polymerase chain reaction to measure Hsa_circRNA_102682 concentration in the serum. Serum transforming growth factor-beta and connective tissue growth factor levels were tested using ELISA. The Pearson correlation test was used to assess the correlations between Hsa_circRNA_102682, transforming growth factor-beta, connective tissue growth factor, homocysteine, and creatinine. RESULT: Hsa_circRNA_102682 was significantly lower in diabetic patients with high levels of homocysteine than in those with normal levels of homocysteine, whereas transforming growth factor-beta and connective tissue growth factor levels were higher in diabetic patients with hyperhomocysteinemia. Hsa_circRNA_102682 was negatively correlated with the levels of transforming growth factor-beta, connective tissue growth factor, homocysteine, and creatinine. Transforming growth factor-beta and connective tissue growth factor were both positively correlated with homocysteine and creatinine. CONCLUSION: Low Hsa_circRNA_102682 was associated with high levels of transforming growth factor-beta and connective tissue growth factor as well as homocysteine and creatinine. These results suggest that Hsa_circRNA_102682 might be related to the pathogenesis of hyperhomocysteinemia in diabetic nephropathy.

Use of the Gout Impact Scale to Evaluate Quality of Life in Chinese Subjects with Gout: A Cross-Sectional Study.

BACKGROUND To use a gout-specific quality of life (QoL) tool, the Gout Impact Scale (GIS), to evaluate characteristics of gout affecting QoL in subjects with gout. MATERIAL AND METHODS In this cross-sectional study, 169 individuals with gout completed the 24-item GIS and a general questionnaire regarding gout characteristics. The reliability and validity of the GIS were verified by Cronbach's a and exploratory factor analysis, respectively. The impact of gout characteristics on the QoL of subjects with gout was assessed by stepwise multiple regression analysis. RESULTS The 169 subjects with gout included 149 (88.2%) men and 20 (11.8%) women, of median age 43 years. The reliability of the GIS was appropriate (0.84-0.90), except for Gout Medication Side Effects (0.69) and Unmet Gout Treatment Need (0.59). Exploratory factor analysis showed that construct validity was acceptable, with a cumulative variance contribution rate of 5 common factors of 70.09% and factor loading >0.5 between each pair of items of the GIS. Univariate analysis showed that male sex was positively correlated with Well-being During Attack (p<0.05), and that source of medical expenses, current cigarette use and drinking were significantly correlated with Unmet Gout Treatment Need (p<0.05 each). A family history of gout, gout flares, and attack frequency were significantly correlated with total GIS, Well-being During Attack, and Gout Concern during Attack (p<0.05 each). Multivariate analysis suggested that history of gouty arthritis, acute attack and attack frequency had a considerable impact on QoL (p<0.05 each). CONCLUSIONS The GIS showed acceptable reliability and validity in identifying associations between poor QoL and gout characteristics.

Structural characterization of the redefined DNA-binding domain of human XPA.

XPA (xeroderma pigmentosum complementation group A), a key scaffold protein in nucleotide excision repair (NER) pathway, is important in DNA damage verification and repair proteins recruitment. Earlier studies had mapped the minimal DNA-binding domain (MBD) of XPA to a region corresponding to residues 98-219. However, recent studies indicated that the region involving residues 98-239 is the redefined DNA-binding domain (DBD), which binds to DNA substrates with a much higher binding affinity than MBD and possesses a nearly identical binding affinity to the full-length XPA protein. However, the structure of the redefined DBD domain of XPA (XPA-DBD) remains to be investigated. Here, we present the crystal structure of XPA-DBD at 2.06 Šresolution. Structure of the C-terminal region of XPA has been extended by 21 residues (Arg211-Arg231) as compared with previously reported MBD structures. The structure reveals that the C-terminal extension (Arg211-Arg231) is folded as an α-helix with multiple basic residues. The positively charged surface formed in the last C-terminal helix suggests its critical role in DNA binding. Further structural analysis demonstrates that the last C-terminal region (Asp217-Thr239) of XPA-DBD might undergo a conformational change to directly bind to the DNA substrates. This study provides a structural basis for understanding the possible mechanism of enhanced DNA-binding affinity of XPA-DBD.

Impairment of decision making and disruption of synchrony between basolateral amygdala and anterior cingulate cortex in the maternally separated rat.

There is considerable evidence to suggest early life experiences, such as maternal separation (MS), play a role in the prevalence of emotional dysregulation and cognitive impairment. At the same time, optimal decision making requires functional integrity between the amygdala and anterior cingulate cortex (ACC), and any dysfunction of this system is believed to induce decision-making deficits. However, the impact of MS on decision-making behavior and the underlying neurophysiological mechanisms have not been thoroughly studied. As such, we consider the impact of MS on the emotional and cognitive functions of rats by employing the open-field test, elevated plus-maze test, and rat gambling task (RGT). Using multi-channel recordings from freely behaving rats, we assessed the effects of MS on the large scale synchrony between the basolateral amygdala (BLA) and the ACC; while also characterizing the relationship between neural spiking activity and the ongoing oscillations in theta frequency band across the BLA and ACC. The results indicated that the MS rats demonstrated anxiety-like behavior. While the RGT showed a decrease in the percentage of good decision-makers, and an increase in the percentage of poor decision-makers. Electrophysiological data revealed an increase in the total power in the theta band of the LFP in the BLA and a decrease in theta power in the ACC in MS rats. MS was also found to disrupt the spike-field coherence of the ACC single unit spiking activity to the ongoing theta oscillations in the BLA and interrupt the synchrony in the BLA-ACC pathway. We provide specific evidence that MS leads to decision-making deficits that are accompanied by alteration of the theta band LFP in the BLA-ACC circuitries and disruption of the neural network integrity. These observations may help revise fundamental notions regarding neurophysiological biomarkers to treat cognitive impairment induced by early life stress.

Multimodal Nanoplatform with ROS Amplification to Overcome Multidrug Resistance in Prostate Cancer via Targeting P-Glycoprotein and Ferroptosis.

Chemotherapy remains the most essential treatment for prostate cancer, but multidrug resistance (MDR) contributes to chemotherapy failure and tumor-related deaths. The overexpression of P-glycoprotein (P-gp) is one of the main mechanisms behind MDR. Here, this work reports a multimodal nanoplatform with a reactive oxygen species (ROS) cascade for gas therapy/ferroptosis/chemotherapy in reversing MDR. The nanoplatform disassembles when responding to intracellular ROS and exerts three main functions: First, nitric oxide (NO) targeted delivery can reverse MDR by downregulating P-gp expression and inhibiting mitochondrial function. Second, ferrocene-induced ferroptosis breaks the redox balance in the tumor intracellular microenvironment and synergistically acts against the tumor. Third, the release of paclitaxel (PTX) is precisely controlled in situ in the tumor for chemotherapy that avoids damage to normal tissues. Excitingly, this multimodal nanoplatform is a promising weapon for reversing MDR and may provide a pioneering paradigm for synergetic cancer therapy.

Intradermal acupuncture in the treatment of rheumatoid arthritis with liver and kidney deficiency syndrome - A sham-controlled, randomized, clinical trial.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is called "immortal cancer", and it affects the quality of life, disability rate and even the survival of patients. This study aimed to observe the clinical efficacy, and adverse reactions of intradermal acupuncture (IA) in the treatment of RA patients with liver and kidney deficiency syndrome. MATERIALS AND METHODS: 132 RA patients were split into an IA group and a sham IA group at a 1:1 ratio. Both groups were assessed before and after the intervention with the assessments: a traditional Chinese medicine (TCM) syndrome evaluation, the Health Assessment Questionnaire (HAQ), the Disease Activity Score 28 (DAS28) and serum C-reactive protein (CRP). RESULTS: There was a statistically significant difference in TCM syndrome evaluation, HAQ, DAS28, and CRP between both groups before and after treatment (P < 0.01). The improvement of TCM syndrome evaluation (95% CI [1.14(0.38-1.89)]; P = 0.001), HAQ (95% CI [2.00(1.00-3.00)]; P = 0.003), and DAS28 (95% CI [0.11(0.02-0.20)]; P = 0.021) in the IA group was more obvious than that in the sham IA group (P < 0.05), except for CRP (95% CI [0.50(- 2.09 to 7.08)], P = 0.786). The difference in CRP outcome changes between the two groups was not statistically significant (P > 0.05). Both groups had comparable results in the implementation of RA in the upper and lower extremity acupoints and did not differ due to different sites (IA group: P = 0.852; sham IA group: P = 0.861). The comparison of effective rate of the upper limb as well as that of the lower limb was statistically significant (P = 0.001). Besides, patients reported no adverse effects. CONCLUSION: The IA intervention was associated with a promising effect on the decrease in RA disease activity and delayed overall disease progression.

Development and validation of a multiparametric MRI-based radiomics signature for distinguishing between indolent and aggressive prostate cancer.

OBJECTIVE: To develop and validate a non-invasive MRI-based radiomics signature for distinguishing between indolent and aggressive prostate cancer (PCa) prior to therapy. METHODS: In all, 139 qualified and pathology-confirmed PCa patients were divided into a training set (n = 93) and a validation set (n = 46). A total of 1576 radiomics features were extracted from the T2WI (n = 788) and diffusion-weighted imaging (n = 788) for each patient. The Select K Best and the least absolute shrinkage and selection operator regression algorithm were used to construct a radiomics signature in the training set. The predictive performance of the radiomics signature was assessed in the training set and then validated in the validation set by receiver operating characteristic curve analysis. We computed the calibration curve and the decision curve to evaluate the calibration and clinical usefulness of the signature. RESULTS: Nine radiomics features were identified to form the radiomics signature. The radiomics score (Rad-score) was significantly different between indolent and aggressive PCa (p < 0.001). The radiomics signature exhibited favorable discrimination between the indolent and aggressive PCa groups in the training set (AUC: 0.853, 95% CI: 0.766 to 0.941) and validation set (AUC: 0.901, 95% CI: 0.793 to 1.000). The decision curve analysis showed that a greater net benefit would be obtained when the threshold probability ranged from 20 to 90%. CONCLUSION: The multiparametric MRI-based radiomics signature can potentially serve as a non-invasive tool for distinguishing between indolent and aggressive PCa prior to therapy. ADVANCES IN KNOWLEDGE: The multiparametric MRI-based radiomics signature has the potential to non-invasively distinguish between the indolent and aggressive PCa, which might aid clinicians in making personalized therapeutic decisions.

An m-Health Intervention for Rheumatoid Arthritis in China ("Rheumatism Center" app): Study Protocol for a Prospective Randomized Controlled Trial.

AIM: To study the feasibility and effectiveness of a m-Health app in improving the management of rheumatoid arthritis. DESIGN: Randomized controlled trial. METHODS: Sixty rheumatoid arthritis participants will be recruited for a 6-month feasibility study. Patients meeting the inclusion criteria will be randomly allocated to receive standard care or standard care plus the m-Health intervention. The primary outcome is the feasibility of a randomized controlled trial. In addition, we will investigate patient satisfaction in using the "Rheumatism Center" app in the intervention group. The secondary outcomes include the scores for the simplified disease activity index, clinical disease activity index, disease activity score 28, health assessment questionnaire and 6-item self-efficacy scale for chronic diseases. The assessments will be performed at baseline and at 4 weeks, 3 months and 6 months after the study is initiated. At the end of the study, we will also collect user views of the app through qualitative interviews. RESULTS: This study is ongoing. The findings of this study will determine the feasibility and effectiveness of m-Health intervention in the management of rheumatoid arthritis, hoping to enhance the awareness of disease management and quality of life for rheumatoid arthritis patients.

Effective Sonosensitizer Delivery by Redox Sensitive Nanoparticles for Prostate Cancer Sonodynamic Therapy via Amplifying Oxidative Stress and Peroxidation.

Sonodynamic therapy (SDT), a novel noninvasive therapeutic modality, provides many noteworthy benefits by generating reactive oxygen species (ROS). However, water-insoluble sonosensitizer delivery strategies have continuously underperformed because of unavoidable toxicity and a short circulation time. In this study, l-cystine derivative-based biocompatible nanoparticles (NPs) that can be used in SDT and induce limited cytotoxicity are designed and synthesized. After ultrasonic (US) irradiation, these sonosensitizer-loaded NPs show highly efficient sonodynamic performance that leads to cytotoxic ROS production. The ability to stop and start ROS generation induced by US irradiation enables accurate temporal and spatial control. In vivo and in vitro experiments are systematically performed to investigate the effects of this system on tumors, and the results indicate remarkable tumor suppression via markedly high persistent oxidative stress that induces peroxidation and endoplasmic reticulum stress. Thus, this novel temporally and spatially controllable ROS generation platform offers a safe and effective theranostic strategy for prostate cancer treatment.

Study on Pain Catastrophizing From 2010 to 2020: A Bibliometric Analysis via CiteSpace.

Purpose: This study aimed to evaluate the global scientific output of research on pain catastrophizing and explore the hotspots and frontiers from 2010 to 2020 using bibliometric methods. Methods: Publications regarding pain catastrophizing published from 2010 to 2020 were extracted from the Web of Science Core Collection. CiteSpace was used to analyze the number of publications, countries, institutions, journals, authors, cited references, and keywords using standard bibliometric indicators. Results: A total of 1,576 publications on pain catastrophizing were retrieved from 2010 to December 31, 2020. The number and rate of the annual publications gradually increased totally. Pain (130) was the most productive journal. Meanwhile, Pain ranked first in the frequency (1,432) and centrality (0.31) of the cited journals. The most productive country and institution in this frequency field were the United States (642) and the University of Washington (73), respectively. Jensen MP (34) was the most prolific author, and Sullivan MJL (1,196) ranked first among the cited authors. In the ranking of frequency in the cited references, the first article was a critical review about pain catastrophizing published by Quartana (100). The keyword "Low back pain" had the highest frequency (556). "Total hip" was identified as a frontier research item for 2016-2020. Conclusion: The findings of this bibliometric study provide the current status and trends in the clinical research of pain catastrophizing and may help researchers to identify hot topics and explore new research directions in this field.

Which Way to Choose for the Treatment of Metastatic Prostate Cancer: A Case Report and Literature Review.

BACKGROUND: Prostate cancer (PCa) is the second most common cancer among males in the world and the majority of patients will eventually progress to the metastatic phase. How to choose an effective way for the treatment of metastatic PCa, especially in the later stage of the disease is still confusing. Herein we reported the case of a patient diagnosed with metastatic PCa and conducted a literature review on this issue. CASE PRESENTATION: A 57-year-old man with metastatic PCa had been managed by Dr. J.P. since April 2012 when the patient was admitted to the Third Affiliated Hospital of Sun Yat-sen University by aggravating frequent urination and dysuria. The prostate-specific antigen (PSA) concentration was 140 ng/ml, and the diagnosis of PCa was confirmed by prostate biopsy, with Gleason score 4 + 5 = 9. Chest CT and bone scan indicated multiple metastases in the lungs and bones. Triptorelin, bicalutamide, zoledronic acid, and docetaxel were then administered, six cycles later, the metastatic tumors in the lungs disappeared and those in the bones lessened significantly, along with a remarkable reduction in PSA level (< 2 ng/ml). Intermittent androgen deprivation was subsequently conducted until August 2018, when the serum PSA level was found to be 250 ng/ml, again docetaxel 75 mg/m2 was administered immediately but the patient was intolerant this time. Instead, abiraterone was administered until March 2019 because of intolerable gastrointestinal side-effects and increasing PSA level. In October 2019, the patient came to our center, a modified approach of docetaxel (day 1 40 mg/m2 + day 8 35 mg/m2) was administered. Luckily, the PSA level decreased rapidly, the bone pain was greatly relieved, and no obvious side effects occurred. However, four cycles later, docetaxel failed to work anymore, the metastatic tumor in the liver progressed. We proposed several regimens as alternatives, but they were soon denied due to the high prices or unavailability or uncertain effect of the drugs. In addition, the patient's condition deteriorated speedily and can no longer bear any aggressive treatment. Finally, the patient died of multiple organ failure in August 2020. CONCLUSION: The experiences of this case provide valuable evidence and reference for the treatment choices of metastatic PCa, in some circumstances modified and advanced regimens may produce unexpected effects.

Intradermal acupuncture for rheumatoid arthritis: study protocol for a randomised controlled trial.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease that severely impacts quality of life. Currently available medications for the treatment of RA have adverse side effects. Emerging evidence suggests that intradermal acupuncture (IA) is feasible and safe for patients, but its application in RA patients has not been examined. Our study aims to explore the efficacy and safety of IA for the treatment of RA. METHODS: This study is a randomised, sham-controlled, patient-outcome assessor-statistician blind trial that aims to evaluate the effects of IA in patients with RA. We will recruit 132 patients aged ≥ 18 years with a diagnosis of RA. Patients will be randomly allocated with a 1:1 ratio to IA or sham IA groups. Both groups will receive basic treatment and nursing routines for RA. The experimental group will receive actual IA treatment, whereas the control group will receive sham IA treatment. All patients will receive one course of treatment (i.e., four consecutive treatment sessions with an intervening 1-day interval). Primary outcomes will be traditional Chinese medicine (TCM) syndromes before and after a treatment course and Health Assessment Questionnaire (HAQ) scores. Secondary outcomes will be disease activity score 28 (DAS28) and levels of serum C-reactive protein (CRP). Outcome measures will be collected pre- and post-treatment. DISCUSSION: This study aims to provide high-quality evidence for the efficacy and safety of IA for treating RA. In addition, the results will provide references for selection of acupoints for other syndromes in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038028 . Registered on 8 September 2020.

MicroRNA-regulated transcriptome analysis identifies four major subtypes with prognostic and therapeutic implications in prostate cancer.

MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor ß, epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53, PTEN and RB, and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance.