Genotype and clinical phenotype characteristics of MAX germline mutation-associated pheochromocytoma/paraganglioma syndrome.

Objective: The aim of this study was to investigate the genotypic and clinical phenotypic characteristics of MAX germline mutation-associated pheochromocytoma (PCC) and paraganglioma (PGL). Methods: We retrospectively analyzed the family investigation data and clinical genetic characteristics of six individuals from three independent families with PCC carrying MAX germline mutations from December 2005 to March 2024. A literature review was then conducted of the six carriers and another 103 carriers from the other 84 families with MAX germline mutations reported previously. Results: There were 109 patients in 87 families with all five exons and 53 types of MAX germline mutations. p.R33* (c.97C>T; 21.1%), p.R75* (c.223C>T; 13.8%), and p.A67D (c.200C>A; 7.3%), which accounted for 42.2% of mutations detected, were the most common mutations. Moreover, 101 (92.7%) patients developed PCCs, including 59 bilateral PCCs and 42 unilateral PCCs, and 19 (18.8%) patients showed metastasis. The mean age at diagnosis was 32.8 ± 12.6 (13-80) years. The male-to-female ratio was 1.3:1. In 11 (10.9%) patients, the PCC was accompanied by chest or abdominal PGL, and one other patient had sole head and neck PGL. Nine (8.3%) patients also had functional pituitary adenomas, 11 (10.9%) developed other neuroendocrine tumors (NETs), and 7 (6.4%) presented with concomitant non-NET. Meanwhile, MAX-p.Q82Tfs*89 and p.E158A mutations are reported for the first time in this study. Conclusion: MAX germline mutations may cause new types of multiple endocrine neoplasia. A comprehensive baseline assessment of neural crest cell-derived diseases is recommended for all individuals with MAX germline mutations. The risk of bilateral and metastatic PCCs should also be considered.

Comprehensive analysis of E47­like factors and verification of ELF4 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most prominent subtype of renal cancer and E47-like factors (ELFs) are important in tumorigenesis; however, the specific role of key ELFs in ccRCC remains unclear. The present study comprehensively analyzed RNA sequencing and clinical data from multiple databases, and identified differentially expressed ELFs (ELF3-5) in ccRCC. The DNA promoter methylation, genetic variation and clinical significance of ELF3-5 in ccRCC were analyzed using the cBioPortal and UALCAN databases. The association between ELF3-5 and multiple immune cell infiltration was analyzed using Tumor Immune Estimation Resource. Subsequently, ELF4 was selected and its association with biological functions was assessed. Cell counting kit-8 (CCK-8), colony formation, Transwell, macrophage chemotaxis and polarization assays were conducted to validate the functions of ELF4. Notably, the mRNA expression levels of ELF4 were significantly upregulated in ccRCC, whereas ELF3 and ELF5 mRNA expression levels were significantly downregulated. Clinical significance analysis revealed that ELF4 showed a high clinical significance with tumor grade, clear cell type A and B subtypes, and incidence rates of amplification in genetic variation. Further analyses indicated that ELF4 may be involved in multiple immune cell differentiation. Additionally, cell experiments revealed that ELF4 inhibition downregulated 769-P and 786-O proliferation, migration and invasion. Knockdown of ELF4 in cancer cells also inhibited M2 macrophage polarization and chemotaxis towards 769-P and 786-O cells. Conclusively, the present findings indicated the clinical significance of ELF4 in ccRCC, and verified its key role in driving cell proliferation, migration and invasion, and promoting M2 macrophage polarization and chemotaxis in ccRCC.

Corrigendum: A randomized controlled trial of a coping-focused family resilience intervention program for breast cancer patients: study protocol.

[This corrects the article DOI: 10.3389/fpsyg.2022.968154.].

Precise application of topical tranexamic acid to enhance endoscopic hemostasis for peptic ulcer bleeding: a randomized controlled study (with video).

BACKGROUND AND AIMS: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. METHODS: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. RESULTS: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded. CONCLUSIONS: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).

Diagnosis and treatment of primary seminoma of the prostate: A case report and review of literature.

BACKGROUND: Primary seminoma of the prostate (PSP) is a rare type of extragonadal germ cell tumour that is easily misdiagnosed, owing to the lack of specific clinical features. It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis. CASE SUMMARY: A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital. A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy. Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles. Further radiotherapy treatment for the local lesion was performed, and the patient had a disease-free survival period of 96 mo. This case was analysed along with 13 other cases of PSP identified from the literature. Only four of the cases (28.6%) were initially confirmed by prostate biopsy. In these cases, imaging examinations showed an enlarged prostate (range 6-11 cm) involving the bladder neck (13/14). Of the 14 total cases, 11 (78.6%) presented typical pure seminoma cell features, staining strongly positive for placental alkaline phosphatase, CD117, and OCT4. The median age at diagnosis was 51 (range 27-59) years, and patients had a median progression-free survival time of 48 (range 6-156) mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy. The remaining three were cases of mixed embryonal tumours with focal seminoma, which had clinical features similar to those of pure PSP, in addition that they also had elevated serum alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase. CONCLUSION: PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck. Further prostate biopsies may aid in proper PSP diagnosis. Cisplatin-based chemotherapy is still the main primary therapy for PSP.

Tripterygium glycosides improve abnormal lipid deposition in nephrotic syndrome rat models.

OBJECTIVE: The purpose of this study was to determine the effect of tripterygium glycosides (TGs) on regulating abnormal lipid deposition in nephrotic syndrome (NS) rats. METHODS: Sprague-Dawley (SD) rats were injected with 6 mg/kg doxorubicin to construct nephrotic syndrome models (n = 6 per group), and then administered with TGs (10 mg/kg·d-1), prednisone (6.3 mg/kg·d-1), or pure water for 5 weeks. Biomedical indexes, such as urine protein/creatinine ratio (PCR), blood urea nitrogen (BUN), serum creatinine (Scr), serum albumin (SA), triglycerides (TG), total cholesterol (TC)were investigated to evaluate the renal injury of rats. H&E staining experiment was used to assess the pathological alterations. Oil Red O staining was used to assess the level of renal lipid deposition. Malondialdehyde (MDA) and glutathione (GSH) were measured to assess the extent of oxidative damage to the kidney. TUNEL staining was used to assess the status of apoptosis in the kidney. Western blot analysis was performed to examine the levels of relevant intracellular signaling molecules. RESULTS: After treatment with TGs, those tested biomedical indexes were significantly improved, and the extent of kidney tissue pathological changes and lipid deposition in the kidney was diminished. Treatment with TGs decreased renal oxidative damage and apoptosis. Regarding the molecular mechanism, TGs significantly increased the protein expression levels of Bcl-2 but decreased the levels of CD36, ADFP, Bax, and Cleaved caspase-3. CONCLUSION: TGs alleviates renal injury and lipid deposition induced by doxorubicin, suggesting that it may be a new strategy for reducing renal lipotoxicity in NS.

Evolution of the Correa's cascade steps: A long-term endoscopic surveillance among non-ulcer dyspepsia and gastric ulcer after H. pylori eradication.

BACKGROUND: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. METHODS: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. RESULTS: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

Design and Implementation of Taizhou Integrated Prostate Screening.

A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60-69, 70-79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years (p < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.

The spatial-temporal distribution and etiological characteristics of hand-foot-and-mouth disease before and after EV­A71 vaccination in Kunming, China, 2017-2020.

After vaccination with enterovirus 71 (EV-A71), the prevalence of hand-foot-and-mouth disease (HFMD) remained high, and the spatial-temporal distribution of enteroviruses changed. Therefore, it is essential to define the temporal features, spatial distributions, and epidemiological and etiological characteristics of HFMD in Kunming. Between 2017 and 2020, a total of 36,540 children were diagnosed with HFMD in Kunming, including 32,754 children with enterovirus-positive clinical samples. Demographic, geographical, epidemiological and etiological data of the cases were acquired and analyzed. Other enteroviruses replaced EV-A71, and the incidence of EV-A71 decreased dramatically, whereas coxsackievirus A6 (CV-A6) and coxsackievirus A16 (CV-A16) had substantial outbreaks in 2018 and 2019, respectively. The major and minor peaks all extended for 2-4 months compared to before vaccination with the EV-A71 vaccine. From 2019 to 2020, CV-A6, as the predominant serotype, showed only a single peak. Although a high incidence of HFMD was observed in Guandu, Chenggong and Xishan, the annual incidence of different enterovirus serotypes was different in different regions. In 2017, other enteroviruses were most prevalent in Shilin. In 2018, CV-A16 and CV-A6 were most prevalent in Luquan and Shilin, respectively. In 2019, CV-A16 was most prevalent in Jinning. In 2020, CV-A6 and coxsackievirus A10 (CV-A10) were most prevalent in Luquan and Shilin, respectively. Meanwhile, the epidemic cycle of CV-A6 and CV-A16 was only 1 year, and CV-A10 and other enteroviruses were potential risk pathogens. The spatial and temporal distribution of HFMD varies at different scales, and the incidence of HFMD associated with different pathogens has obvious regional differences and seasonal trends. Therefore, research on multivalent combined vaccines is urgently needed, and proper preventive and protective measures could effectively control the incidence of HFMD-like diseases.

A randomized controlled trial of a coping-focused family resilience intervention program for breast cancer patients: Study protocol.

Background: Breast cancer patients and their families are under various pressures in the process of disease diagnosis and treatment, which seriously threaten their physical and mental health. Findings from existing research suggest that good family resilience can help breast cancer families better adapt and cope with adversity and challenges. However, there are only a few intervention studies on family resilience and no intervention studies on resilience among the families of breast cancer patients. Therefore, this study aims to explore appropriate measures to improve the resilience level of breast cancer families and help them better cope with the disease. Objective: The purpose of this study protocol is to demonstrate a coping-focused family resilience intervention to increase the level of resilience in the families of breast cancer patients and help them better cope with adversity. Methods: The trial will recruit 80 breast cancer families and randomly assign them to experimental and control groups in a 1:1 ratio. The control group will receive routine care, and the intervention group will receive a 6-week one-on-one online family resilience intervention based on the control group. Two groups of subjects will be assessed at baseline and at 1 week, 1 month, and 3 months after the intervention. The primary outcome is family resilience, and the secondary outcomes are coping style, social support, family disease burden, and levels of anxiety and depression. Expected results: We hypothesized that after the intervention, the intervention group would have significantly higher levels of family resilience than the preintervention and control groups. In the intervention group, other aspects related to family resilience, such as family disease burden and anxiety and depression levels of patients and their families, were significantly alleviated, and disease coping and social support levels were improved accordingly. Discussion: If the program works, it can help breast cancer families identify family strengths and resources to proactively address challenges so that families can successfully navigate the crisis and patient and family recovery can be facilitated. It can also provide a practical path for clinical workers to help breast cancer families adjust rationally. Clinical Trial Registration: This study has been registered in the Chinese Clinical Trials Registry (Registration Number: http://www.chictr.org.cn/ChiCTR2100052108).

Analysis of the Factors Related to Intracranial Infection after Brain Tumor Surgery.

In order to explore the factors related to intracranial infection after brain tumor surgery, a retrospective analysis is conducted in this study. According to the patients with intracranial infection after brain tumor surgery in our hospital from January 2020 to October 2020, clinical data are divided into different groups and some indicators are put into the multiple regression model for multivariate analysis. The factors related to intracranial infection after brain tumor surgery are analyzed, and the clinical effect of a detailed management plan based on the abovementioned risk factors to prevent intracranial infection in patients after brain tumor surgery is observed. Multiple regression models demonstrate that complicated underlying diseases, operation time, and intraoperative blood loss are independent risk factors for postoperative intracranial infection.

Clinical Benefit of Niraparib to TKI/mTORi-Resistance Metastatic ccRCC With BAP1-Frame Shift Mutation: Case Report and Literature Review.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The top four mutant genes affecting the occurrence and progression of ccRCC are VHL, PBRM1, BAP1, and SETD2, respectively. Tyrosine kinase/mammalian target of rapamycin inhibitors (TKI/mTORis) with or without immunotherapy are the standard and effective therapy to metastatic ccRCC. Once TKI/mTORis fail to ccRCC, there is still a lack of other effective therapies. In this study, we reported a case in which a metastatic ccRCC patient (T2aN1M1) presented resistance after a 28-month treatment by sorafenib-axitinib-everolimus (TKI-TKI-mTORi). Subsequently, a frame shift pathogenic mutation, c.799_800del (p.Q267fs) in the exon10 of BAP1 in ccRCC, was revealed by targeted sequencing. Oral administration of nilapanib (PARP inhibitor) was further given, which may provide a new therapy for TKI/mTORi-resistance metastatic ccRCC. Fortunately, a partial response has been achieved and lasted for 5 months. Since the frequency of BAP1 mutations in ccRCC patients was approximately 10%-20%, as reported previously, we also tried to explore the potential mechanisms benefitting from the nilapanib. Moreover, the literature concerning BAP1 mutation and associated cancers including ccRCC is reviewed.

Design, synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties.

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity towards other S-adenosyl-L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.

Age, male sex, smoking and metabolic syndrome as risk factors of advanced colorectal neoplasia for fecal immunochemical test negative patients.

BACKGROUND: Fecal immunochemical test (FIT) is worldwide strategy for colorectal cancer screening. The subjects with negative FIT still have the risk of an advanced colorectal neoplasia (AN), including adenoma with villous histology, high grade dysplasia or larger than 1 cm in size, or adenocarcinoma. The study determined the risk factors associated with AN in FIT-negative subjects. METHODS: The study included asymptomatic subjects who received health checkup colonoscopy and have provided FIT study within 6 months prior to colonoscopy. The risk factors to have AN in cases with negative FIT were analyzed. The numbers of colonoscopies needed to detect one AN were calculated for the subjects with different risk factors. RESULTS: There were 1411 cases, 85 with positive FIT and 1326 with negative FIT within 6 months before colonoscopy. In FIT positive and FIT negative cases, 45.9% and 34.6% were found to have colorectal adenoma, while 20.2% and 4.6% had AN, respectively. The univariate and multivariate logistic regression analyses showed that age more than 50 years old, male sex, smoking history and metabolic syndrome were the significant risk factors to have AN in the FIT negative cases. For cases with negative FIT to have these risk factors, the number of colonoscopies needed to detect one AN was 3.7, lower than 4.5 of the cases with positive FIT. CONCLUSION: For the cases with negative FIT, colonoscopy screening should be considered for those male patients over 50 years old, with a history of smoking and metabolic syndrome to detect AN.

Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate.

Delicaflavone (DF), a natural active ingredient from Selaginella doederleinii Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated the pharmacokinetic profile of DF in rats using a validated HPLC-MS/MS methods, as well as its human serum albumin (HSA) binding properties through multi-spectroscopic and in silico methods. The results showed that DF was rapidly eliminated and had a widespread tissue distribution after intravenous administration. DF showed linear dynamics in the dose range of 30-60 mg/kg and poor oral bioavailability. The major distribution tissues of DF were the liver, lungs, and kidneys. Ultraviolet and fluorescence spectroscopy and molecular docking demonstrated that DF had a static quenching effect on HSA, with one binding site, and relatively strong binding constants. Thermodynamic analysis of the binding data revealed that hydrogen bonding and van der Waals interactions played major roles in binding. The results of this study further our understanding of the pharmacokinetic and plasma protein binding properties of the potential anticancer agent DF and shed light on pharmacological strategies that may be useful for the development of novel cancer therapeutics.

Optimal Intervals of Ultrasonography Screening for Early Diagnosis of Hepatocellular Carcinoma in Taiwan.

Importance: There are different clinical practices regarding ultrasonography screening intervals for hepatocellular carcinoma (HCC) despite recommendations from international guidelines. Objective: To evaluate whether ultrasonography screening using intervals suggested by international guidelines is associated with cancer stage shifting, reductions in mortality, and improved quality of life (QoL) for patients with HCC. Design, Setting, and Participants: This nationwide comparative effectiveness research study estimated lifetime survival functions using interlinkages of 3 databases from Taiwan-the Taiwan National Health Insurance, Taiwan National Cancer Registry, and National Mortality Registry-combined with QoL measurements obtained from National Cheng Kung University Hospital. In total, 114 022 patients listed as having newly diagnosed HCC from 2002 through 2015 in the Taiwan National Cancer Registry were followed up until 2017. The QoL values of 1059 patients with HCC who visited National Cheng Kung University Hospital were prospectively measured with the European QoL-5 dimensions questionnaire from 2011 through 2019. Patients were categorized based on the time between their last ultrasonography screening and the index date (90 days prior to HCC diagnosis) as 1 of 5 subcohorts: 6 months (0-6 months), 12 months (7-12 months), 24 months (13-24 months), 36 months (25-36 months), and longer than 36 months (no screening in the previous 3 years). Data were analyzed from April 2020 to April 2021. Main Outcomes and Measures: Life expectancy, quality-adjusted life expectancy, and loss of life expectancy or loss of quality-adjusted life expectancy compared with age-, sex-, and calendar year-matched cohorts. Results: There were 59 194 patients with Barcelona Clinic Liver Cancer staging information, including 42 081 men (mean [SD] age, 62.2 [12.6] years) and 17 113 women (mean [SD] age, 69.0 [11.2] years). There was a consistent trend showing that the longer the interval between ultrasonography examinations, the higher the loss of life expectancy and loss of quality-adjusted life expectancy for both sexes. Loss of quality-adjusted life expectancy values for male subcohorts were 10.0 (95% CI, 9.1-10.9) quality-adjusted life-years (QALYs) for ultrasonography screening intervals of 6 months, 11.1 (95% CI, 10.4-11.8) QALYs for 12 months, 12.1 (95% CI, 11.5-12.7) QALYs for 24 months, 13.1 (95% CI, 12.6-13.6) QALYs for 36 months, and 14.6 (95% CI, 14.2-15.0) QALYs for longer than 36 months. Loss of quality-adjusted life expectancy values for female subcohorts were 9.0 (95% CI, 8.3-9.6) QALYs for 6 months, 9.7 (95% CI, 9.2-10.2) QALYs for 12 months, 10.3 (95% CI, 9.8-10.7) QALYs for 24 months, 10.7 (95% CI, 10.2-11.1) QALYs for 36 months, and 11.4 (95% CI, 11.0-11.8) QALYs for longer than 36 months. Patients with underlying hepatitis B virus infection or cirrhosis had the greatest improvement in life expectancy with shorter screening intervals. Conclusions and Relevance: Regular ultrasonography screening with intervals less than 6 to 12 months may be associated with early detection of HCC, save lives, and improve the quality of life for patients with HCC from a lifetime perspective.

Intraarticular Injection of Infliximab-Loaded Thermosensitive Hydrogel Alleviates Pain and Protects Cartilage in Rheumatoid Arthritis.

PURPOSE: Pain and cartilage destruction caused by rheumatoid arthritis (RA) are major challenges during clinical treatment. Traditional systemic administration not only has obvious side effects but also provides limited relief for local symptoms in major joints. Local delivery of therapeutics for RA treatment is a potential strategy but is limited by rapid intraarticular release. MATERIALS AND METHODS: In this study, we prepared a thermoresponsive injectable hydrogel by mixing pluronic F127 (F127) and hyaluronic acid (HA) with poly (γ-glutamic acid) (PGA) incorporating infliximab (IFX), a new generation monoclonal antibody drug. We investigated the biocompatibility of the hydrogel and its IFX release profile. In vivo, we studied the clinical manifestations (articular skin temperature and joint diameter), detected cytokines in the synovial fluid and cartilage, performed behavioral studies on pain relief, and evaluated the cartilage protection effect. RESULTS: A thermoresponsive hydrogel was successfully prepared by mixing F127, HA, and PGA with injectable properties. The F127-HA-PGA hydrogel had a porous structure with interconnected pores. The infliximab-loaded thermosensitive hydrogel exhibited good biocompatibility and biodegradability and sustained release properties. Intraarticular injection of the IFX-loaded F127-HA-PGA hydrogel could alleviate the expression of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-17 (IL-17), in the synovial fluid and cartilage as well as relieve pain and inhibit cartilage destruction in RA. CONCLUSION: The double effect on pain relief and cartilage protection indicated the significant potential of the IFX-loaded injectable hydrogel for RA treatment in major joint lesions.

The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6.

BACKGROUND: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. METHODS: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4th-28th day after the first bleeding episode. RESULTS: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01). CONCLUSIONS: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.

Lead Time Bias May Contribute to the Shorter Life Expectancy in Post-colonoscopy Colorectal Cancer.

BACKGROUND: The long-term outcomes of post-colonoscopy colorectal cancer have varied in previous studies. Our nationwide cohort analysis estimated expected years of life lost to adjust for lead time bias. AIM: We recalculated the long-term outcomes for post-colonoscopy and detected colorectal cancer. METHODS: Patients with colorectal cancer registered in the Taiwan Cancer Registry between 2002 and 2009 were enrolled. The detected group included 22,169 cases of colorectal cancer confirmed within 6 months after a colonoscopy. The post-colonoscopy group included 1653 cancer patients who received a colonoscopy 6-60 months before diagnosis. Patients were followed up until 2011. We simulated age-, sex-, and calendar year-matched referents from life tables in the Taiwan National Vital Statistics using a Monte Carlo method. The life expectancy and expected years of life lost of the cancer patients were obtained from extrapolation of the logit transformation of the survival ratio between the cancer cohorts and the referent groups. RESULTS: Post-colonoscopy colorectal cancer had shorter life expectancies than detected cancer (stages 2-4: 13.6 vs. 16.1 years; 8.7 vs. 12.6 years; 2.1 vs. 4.1 years, p < 0.001). The loss-of-life expectancy did not show this trend after adjusting for lead time bias. Post-colonoscopy colorectal cancer was found at an older age, more often proximal, and was associated with previous endoscopic polypectomy procedures (p < 0.001). CONCLUSIONS: Post-colonoscopy colorectal cancer leads to a shorter life expectancy, which appears partially explained by the presence of lead time bias. Quality assurance for colonoscopy and close surveillance for high risk groups would reduce post-colonoscopy colorectal cancer.

Gonorrhea and chlamydia prevalence in different anatomical sites among men who have sex with men: a cross-sectional study in Guangzhou, China.

BACKGROUND: A high rectal and oropharyngeal sexually transmitted infection (STI) burden has been reported among men who have sex with men (MSM) in many regions, but little data exists on rectal and oropharyngeal STIs among MSM in China. The purpose of this study was to determine the prevalence of gonorrhea and chlamydia at different anatomic sites among MSM in Guangzhou, China. METHODS: We recruited a cross-sectional sample of MSM in one Chinese city and collected detailed information about socio-demographic characteristics and sexual behaviors. Men had urine, rectal, and pharyngeal swab samples tested for gonorrhea and chlamydia using nucleic acid amplification tests (NAAT). Univariate and multivariate logistic regressions were used to evaluate factors associated with gonorrhea and chlamydia. Among men without any STI symptoms, we also examined the prevalence of gonorrhea and chlamydia by anatomical site. RESULTS: We enrolled 463 men between January 2015 and March 2017. A total of 58/463 (12.5%) of men had gonorrhea and 84/463 (18.1%) had chlamydia. MSM with gonorrhea were more likely to have been recruited from the STI clinic (OR 3.41, 95% CI 1.94-5.99), living with HIV (OR 2.41, 95% CI 1.18-4.92), diagnosed had STI co-infection (OR 2.55, 95% CI 1.39-4.69). MSM with chlamydia were more likely to be students (OR 1.8, 95% CI 0.99-3.39). Most gonorrhea (34/58, 59%) and chlamydia (64/84, 76%) infections were not associated with STI symptoms. CONCLUSION: Asymptomatic gonorrhea and chlamydia infection were common in this sample of Chinese MSM. Further research is necessary to determine optimal STI screening programs.