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Colonic diverticulitis is a common gastrointestinal disease which can be acute or chronic in course. In this paper we report the management of a patient with chronic colonic diverticulitis. The patient had an atypical clinical presentation, whose imaging showed a high likelihood of occupying lesions. PET/CT showed hypermetabolism focus and colonoscopy saw mucosal thickening, pathological return of inflammation in the acute phase, which were difficult in differential diagnosis with colorectal cancer and inflammatory bowel disease. After comprehensive consideration, follow-up observation was recommended and the diagnosis was finally clarified. The management of this patient demonstrates the importance of evidence-based medicine in the diagnosis and treatment of diseases.

Hydrogels are widely used in many applications due to their hydration environment and tunable properties (e.g., mechanical, chemical, and biocompatibility) similar to that of natural extracellular matrices. Upon exposure to some specific stimuli, hydrogels can undergo shape deformation or even state transitions, and these stimulus-responsive hydrogels are constantly being developed, with promising applications in biomedicine, micromechanics, soft actuators, and robotics. In recent years, there have been increasing studies on stimulus-responsive smart hydrogels, which incorporate driving units in previously studied high-strength hydrogels, allowing the hydrogels to not only retain their original excellent mechanical properties, but also have good driving properties. Herein, by analyzing the driving mechanism and driving modes of hydrogels, the latest progress in smart hydrogels with six different driving modes, such as temperature-driven, light-driven, pH-driven, substance-specific-driven, magnetic-driven, and hybrid-driven hydrogels, is explored. Also, the preparation, structure, and properties of hydrogels are reviewed in detail. Finally, the current challenges and future prospects for shape-deformation stimulus-responsive hydrogels are discussed. [ABSTRACT FROM AUTHOR]

Displaced intra-articular calcaneus fractures (DIACFs) are difficult injuries to treat and are often encountered by orthopedic surgeons. For DIACFs treated nonoperatively or with open reduction internal fixation (ORIF), a common complication is painful subtalar arthritis and the need for a secondary subtalar fusion, which prolongs the overall recovery time. One treatment option to address this sequela involves ORIF with subtalar fusion as the primary treatment. We describe a reproducible, minimally invasive surgical technique for primary ORIF with subtalar fusion when the calcaneal tuberosity is amendable to cannulated screw fixation to treat these complex calcaneal fractures. Our technique offers advantages compared to other techniques in that it avoids screw traffic, allows easy bony compression of the subtalar joint, and minimizes soft tissue damage via percutaneous screw fixation. Fourteen fractured calcanei in 12 patients underwent our technique and all achieved bony union with a median time to fusion of 107.5 days (range, 54–530 days). Eight patients returned to work with the remaining 4 patients having an unknown work status at last follow-up, although 2 of these 4 patients resumed normal activities. Only 1 patient experienced a complication, which was an infection after achieving bony union, and was treated with successful hardware removal and our infection protocol. Overall, we conclude our surgical technique offers a successful option in the treatment of DIACFs when the calcaneal tuberosity is amendable to cannulated screw fixation. [ABSTRACT FROM AUTHOR]

The burden of digestive cancers is increasing worldwide. The Global Cancer Observatory (GLOBOCAN) 2020 and the Global Burden of Disease (GBD) 2019 are two primary cancer databases, which have a significant impact on policy formulation and resource allocation. We aim to compare the incidence and mortality of digestive cancers between them. Digestive cancer (esophageal, stomach, colorectal, liver, gallbladder and pancreatic cancer) incidence was obtained from the Cancer Today and GBD 2019 result tool. The top five countries with the most or minor difference between GLOBOCAN 2020 and GBD 2019 in age‐standardized incidence rates (ASIRs) of digestive cancers were identified. A systematic search on the incidence of specific digestive cancer in selected countries from PubMed and Embase was conducted, and 20 of 281 publications were included. The most significant differences in digestive cancers incidence were commonly found in Asian countries (70%), particularly Indonesia, Vietnam and Myanmar, located in Southeast Asia. The ASIRs for most digestive cancers, except liver cancer, in GLOBOCAN 2020 were higher than those in GBD 2019. Gallbladder cancer had the highest average ratio, followed by liver cancer. The most commonly used standard population was Segi's standard population, followed by the World Health Organization standard population. The data sources nor the processing methods of GLOBOCAN 2020 and GBD 2019 were not similar. Low‐ and middle‐income countries without population‐based cancer registries were more likely to have selection bias in data collection and amplify regional variations of etiological factors. Better judgments on the quality of cancer data can be made. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to investigate the role of N6‐methyladenosine (m6A) modification in the progression of rheumatoid arthritis (RA). Methods: Peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls were collected. The expression of m6A modification‐related proteins and m6A levels were detected using polymerase chain reaction (PCR), western blot, and m6A enzyme‐linked immunosorbent assay (ELISA). The roles of methyltransferase‐like 14 (METTL14) in the regulation of inflammation in RA was explored using methylated RNA immunoprecipitation (MeRIP) sequencing and RNA immunoprecipitation assays. Collagen antibody‐induced arthritis (CAIA) mice were used as an in vivo model to study the role of METTL14 in the inflammation progression of RA. Results: We found that m6A writer METTL14 and m6A levels were decreased in PBMCs of patients with active RA and correlated negatively with the disease activity score using 28 joint counts (DAS28). Knockdown of METTL14 downregulated m6A and promoted the secretion of inflammatory cytokines interleukin 6 (IL‐6) and IL‐17 in PBMCs of patients with RA. Consistently, METTL14 knockdown promoted joint inflammation accompanied by upregulation of IL‐6 and IL‐17 in CAIA mice. MeRIP sequencing and functional studies confirmed that tumor necrosis factor α induced protein 3 (TNFAIP3), a key suppressor of the nuclear factor‐κB inflammatory pathway, was involved in m6A‐regulated PBMCs. Mechanistic investigations revealed that m6A affected TNFAIP3 expression by regulation of messenger RNA stability and translocation in TNFAIP3 protein coding sequence. Conclusions: Our study highlights the critical roles of m6A on regulation of inflammation in RA progression. Treatment strategies targeting m6A modification may represent a new option for management of RA. [ABSTRACT FROM AUTHOR]

Background: Prescription drug overdose and misuse has reached alarming numbers. A persistent problem in clinical care is lack of easy, immediate access to all relevant information at the actionable time. Prescribers must digest an overwhelming amount of information from each patient's record as well as remain up-to-date with current evidence to provide optimal care. This study aimed to describe prescriber response to a prospective clinical decision support intervention designed to identify patients at risk of adverse events associated with misuse of prescription opioids/benzodiazepines and promote adherence to clinical practice guidelines. Methods: This study was conducted at a large multi-center healthcare system, using data from the electronic health record. A prospective observational study was performed as clinical decision support (CDS) interventions were sequentially launched (January 2016–July 2019). All data were captured from the medical record prospectively via the CDS tools implemented. A consecutive series of all patient encounters including an opioid/benzodiazepine prescription were included in this study (n = 61,124,172 encounters; n = 674,785 patients). Physician response to the CDS interventions was the primary outcome, and it was assessed over time using control charts. Results: An alert was triggered in 23.5% of encounters with a prescription (n = 555,626). The prescriber decision was influenced in 18.1% of these encounters (n = 100,301). As the number of risk factors increased, the rate of decision being influenced also increased (p = 0.0001). The effect of the alert differed by drug, risk factor, specialty, and facility. Conclusion: The delivery of evidence-based, patient-specific information had an influence on the final prescription in nearly 1 in 5 encounters. Our intervention was sustained with minimal prescriber fatigue over many years in a large and diverse health system. [ABSTRACT FROM AUTHOR]

Background: Focal cartilage lesions of the knee remain a difficult entity to treat. Current treatment options include arthroscopic debridement, microfracture, autograft or allograft osteochondral transplantation, and cell-based therapies such as autologous chondrocyte transplantation. Osteochondral transplantation techniques restore the normal topography of the condyles and provide mature hyaline cartilage in a single-stage procedure. However, clinical outcomes comparing autograft versus allograft techniques are scarce. Purpose: To perform a comprehensive systematic review and meta-analysis of high-quality studies to evaluate the results of osteochondral autograft and allograft transplantation for the treatment of symptomatic cartilage defects of the knee. Study Design: Systematic review and meta-analysis; Level of evidence, 2. Methods: A comprehensive search of the literature was conducted using various databases. Inclusion criteria were level 1 or 2 original studies, studies with patients reporting knee cartilage injuries and chondral defects, mean follow-up ≥2 years, and studies focusing on osteochondral transplant techniques. Exclusion criteria were studies with nonknee chondral defects, studies reporting clinical outcomes of osteochondral autograft or allograft combined with other procedures, animal studies, cadaveric studies, non–English language studies, case reports, and reviews or editorials. Primary outcomes included patient-reported outcomes and failure rates associated with both techniques, and factors such as lesion size, age, sex, and the number of plugs transplanted were assessed. Metaregression using a mixed-effects model was utilized for meta-analyses. Results: The search resulted in 20 included studies with 364 cases of osteochondral autograft and 272 cases of osteochondral allograft. Mean postoperative survival was 88.2% in the osteochondral autograft cohort as compared with 87.2% in the osteochondral allograft cohort at 5.4 and 5.2 years, respectively (P =.6605). Patient-reported outcomes improved by an average of 65.1% and 81.1% after osteochondral autograft and allograft, respectively (P =.0001). However, meta-analysis revealed no significant difference in patient-reported outcome percentage change between osteochondral autograft and allograft (P =.97) and a coefficient of 0.033 (95% CI, –1.91 to 1.98). Meta-analysis of the relative risk of graft failure after osteochondral autograft versus allograft showed no significant differences (P =.66) and a coefficient of 0.114 (95% CI, –0.46 to 0.69). Furthermore, the regression did not find other predictors (mean age, percentage of female patients, lesion size, number of plugs/grafts used, and treatment location) that may have significantly affected patient-reported outcome percentage change or postoperative failure between osteochondral autograft versus allograft. Conclusion: Osteochondral autograft and allograft result in favorable patient-reported outcomes and graft survival rates at medium-term follow-up. While predictors for outcomes such as mean age, percentage of female patients, lesion size, number of plugs/grafts used, and treatment location did not affect the comparison of the 2 cohorts, proper patient selection for either procedure remains paramount to the success and potentially long-term viability of the graft. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) by bacteria is a serious global threat, and a rapid, high-throughput, and easy-to-use phenotypic antimicrobial susceptibility testing (AST) method is essential for making timely treatment decisions and controlling the spread of antibiotic resistant micro-organisms. Traditional culture-based methods are time-consuming, and their capability to screen against a large number of different conditions is limited; meanwhile genotypic based methods, including sequencing and PCR based methods, are constrained by rarely identified resistance genes and complicated resistance mechanisms. Here, a combinatorial-screening SlipChip (cs-SlipChip) containing 192 nanoliter-sized compartments is developed which can perform high-throughput phenotypic AST within three hours by monitoring the bacterial growth within nanoliter-sized droplets with bright-field imaging and analyzing the changes in bacterial number and morphology. The minimum inhibitory concentration (MIC) of Escherichia coli ATCC 25922 against four antibiotics (ampicillin, ciprofloxacin, ceftazidime, and nitrofurantoin) can be measured in one chip within 3 hours. Furthermore, five antibiotic-resistant E. coli strains were isolated from patients diagnosed with urinary tract infections (UTIs), and an individual isolate was tested using four antibiotics and eleven antibiotic combinations simultaneously with three different concentrations of each. The results from the cs-SlipChip agree with those of a VITEK 2 automated system. This cs-SlipChip provides a practical high-throughput and rapid phenotypic method for AST and can also be used to screen different chemicals and antibiotic combinations for the treatment of multiple antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Enhanced recovery after surgery (ERAS) has decreased hospital opioid use, but less attention has been directed towards its impact on clinic burden with respect to post-operative care. Our objective was to determine the impact of an ERAS protocol on post-operative opioid prescribing, and the subsequent number of pain medication refill requests and unscheduled patient-provider interactions in the 30-day post-operative period. IRB-approved retrospective study comparing post-operative opioid prescription practices 10 months before and 10 months after ERAS protocol implementation after minimally invasive gynecologic surgery. Opioid doses in morphine milligram equivalents (MMEs), number of unscheduled visits, and phone calls were compared before and after ERAS implementation. A total of 791 patients were included; 445 without and 346 with ERAS implementation. ERAS was associated with higher rates of same day discharge (49% vs 39%, p = 0.003) and lower readmission rates (2.0% vs 5.6%, p = 0.011). Post-operatively, patients who received the ERAS protocol were prescribed less opioids (197.8 vs. 223.5 MMEs, p = 0.0087). There was a trend towards less refill requests with ERAS (1.7% vs 3.6%, p = 0.11). ERAS was associated with a decreased number of post-operative phone calls (38% vs 46%, p = 0.023), including calls for pain (10% vs 16%, p = 0.021), and fewer unscheduled visits related to pain (1.5% vs 5.8%, p = 0.001). Implementation of the ERAS protocol resulted in a decrease in post-operative opioid prescribing. Despite the lower amount of prescribed post-operative opioids, the ERAS protocol translated into a decrease in the need for post-operative interactions with the clinic staff, specifically encounters associated with pain. • ERAS protocol is associated with a reduction in intra-operative opioid use and opioids prescribed for post-operative pain. • Lower doses of post-operative opioids following minimally invasive gynecologic surgery do not increase clinic staff burden. • Patients who receive ERAS protocol make less calls and visits related to pain despite lower doses of opioids prescribed. [ABSTRACT FROM AUTHOR]

Digital biological analysis compartmentalizes targets of interest, such as nucleic acids, proteins, and cells, to a single event level and performs detection and further investigation. Microfluidic-based digital biological analysis methods, including digital PCR, digital protein analysis, and digital cell analysis, have demonstrated superior advantages in research applications and clinical diagnostics. However, most of the methods are still based on a one-step "divide and detect" strategy, and it is challenging for these methods to perform further parallel manipulation of reaction partitions to achieve "divide, manipulate, and analyze" capabilities. Here, we present a parallel multistep digital analysis (PAMDA) SlipChip for the parallel multistep manipulation of a large number of droplets for digital biological analysis, demonstrated by the quantification of SARS-CoV-2 nucleic acids by a two-step digital isothermal amplification combined with clustered regularly interspaced short palindromic repeats (CRISPR). This PAMDA SlipChip utilizes a "chain-of-pearl" channel with a self-partitioning droplet formation mechanism that does not require the precise alignment of microfeatures for fluidic loading as the traditional SlipChip design. This device can first generate 2400 3.2 nanoliter droplets to perform digital loop-mediated isothermal amplification (LAMP) and then deliver reagents containing Cas12a protein and crRNA to each individual partition in parallel to simultaneously initiate digital CRISPR detection by a simple multistep slipping operation. This PAMDA SlipChip not only provides a promising tool to perform digital CRISPR with a flexible assay and workflow design but can also be applied for a broad range of applications in digital biological analysis that require multistep manipulation of partitions in parallel. [ABSTRACT FROM AUTHOR]

Backgrounds: Inflammation underlies the mechanism of different kinds of heart disease. Cytoplasmic membrane localized N‐terminal fragment of gasdermin‐D (GSDMD‐N) could induce inflammatory injury to cardiomyocyte. However, effects and dynamic changes of GSDMD during the process of lipopolysaccharide (LPS) related inflammatory stress induced cardiomyocyte injury are barely elucidated to date. In this study, LPS related cardiomyocyte injury was investigated based on potential interaction of GSDMD‐N induced mitochondrial injury and mitophagy mediated mitochondria quality control. Methods: HL‐1 cardiomyocytes were treated with LPS and Nigericin to induce inflammatory stress. The dual‐fluorescence‐labelled GSDMD expressed HL‐1 cardiomyocytes were constructed to study the translocation of GSDMD. The mitochondrial membrane potential (MMP) was measured by JC‐1 staining. Mitophagy and autophagic flux were recorded by transmission electron microscopy and fluorescent image. Results: GSDMD‐N showed a time‐dependent pattern of translocation from mitochondria to cytoplasmic membrane under LPS and Nigericin induced inflammatory stress in HL‐1 cardiomyocytes. GSDMD‐N preferred to localize to mitochondria to permeablize its membrane and dissipate the MMP. This effect couldn't be reversed by cyclosporine‐A (mPTP inhibitor), indicating GSDMD‐N pores as alternative mechanism underlying MMP regulation, in addition to mitochondrial permeability transition pore (mPTP). Moreover, the combination between GSDMD‐N and autophagy related Microtubule Associated Protein 1 Light Chain 3 Beta (LC3B) was verified by co‐immunoprecipitation. Besides, mitophagy alleviating GSDMD‐N induced mitochondrial injury was proved by pre‐treatment of autophagy antagonist or agonist in GSDMD‐knock out or GSDMD‐overexpression cells. A time‐dependent pattern of GSDMD translocation and mitochondrial GSDMD targeted mitophagy were verified. Conclusion: Herein, our study confirmed a crosstalk between GSDMD‐N induced mitochondrial injury and mitophagy mediated mitochondria quality control during LPS related inflammation induced cardiomyocyte injury, which potentially facilitating the development of therapeutic target to myocardial inflammatory disease. Our findings support pharmaceutical intervention on enhancing autophagy or inhibiting GSDMD as potential target for inflammatory heart disease treatment. [ABSTRACT FROM AUTHOR]

Aims: Right ventricular pacing (RVP) dependence could impair left ventricular ejection fraction (LVEF). This study aimed to illuminate the relationship between RVP proportion and LVEF, as well as disclosing independent predictors of RVP dependence. Methods and results: Patients indicated for permanent pacemaker implantation were included (2016–2020). The ventricular pacing lead was placed in right ventricular apex or septum. Pacing mode programming followed universal standard. Electrocardiographic, echocardiographic, and serological parameters were collected. RVP dependence was defined according to its influence on LVEF. This study was of case–control design. Included patients were matched by potentially confounding factors through propensity score matching. A total of 1183 patients were included, and the mean duration of follow‐up was 24 months. Percentage of RVP < 80% hardly influenced LVEF; however, LVEF tended to decrease with higher RVP proportion. High degree/complete atrioventricular block (AVB) [odds ratio (OR) = 5.71, 95% confidence interval (CI): 3.66–8.85], atrial fibrillation (AF) (OR = 2.04, 95% CI: 1.47–2.82), percutaneous coronary intervention (PCI) (OR = 2.89, 95% CI: 1.24–6.76), maximum heart rate (HRmax) < 110 b.p.m. (OR = 2.74, 95% CI: 1.58–4.76), QRS duration > 120 ms (OR = 2.46, 95% CI: 1.42–4.27), QTc interval > 470 ms (OR = 2.01, 95% CI: 1.33–3.05), and pulmonary artery systolic pressure (PASP) > 40 mmHg (OR = 1.93, 95% CI: 1.46–2.56) were proved to predict RVP dependence. Conclusions: High RVP percentage (>80%) indicating RVP dependence significantly correlates with poor prognosis of cardiac function. High degree/complete AVB, AF, ischaemic aetiology, PCI history, HRmax < 110 b.p.m., QRS duration > 120 ms, QTc interval > 470 ms, and PASP > 40 mmHg were verified as independent risk factors of RVP dependence. [ABSTRACT FROM AUTHOR]

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease with unknown etiology. CCN1, an extracellular matrix-associated protein, is associated with carcinoma, inflammation, liver fibrosis, and even autoimmune diseases. However, the role that CCN1 plays in AIH has remained undetermined. In this study, expression of CCN1 in liver was detected by real-time PCR, western blot and immunohistochemistry (IHC). CCN1 level in serum was detected by ELISA. Diagnostic value of CCN1 was determined by receiver operating characteristic (ROC) curve analysis. CCN1 conditional knockout (CCN1 fl/fl Cre+) mice were generated by mating CCN1 fl/fl C57BL/6J and CAG-Cre-ERT C57BL/6J mice. Autoimmune hepatitis mice model was induced by concanavalin A (ConA). IKKα/β, IκBα, NF-κB p65 and Akt phosphorylation were determined by western blot. NF-κB p65 nuclear translocation was examined by immunofluorescence. Here, we found that CCN1 was over-expressed in hepatocytes of AIH patients. CCN1 level also increased in serum of AIH patients compared to healthy controls (HC). ROC curve analysis results showed that serum CCN1 was able to distinguish AIH patients from HD. In ConA induced hepatitis mice model, CCN1 conditional knockout (CCN1 fl/fl Cre+) attenuated inflammation by reducing ALT/AST level and IL-6 expression. In vitro , CCN1 treatment dramatically induced IL-6 production in LO2 cells. Moreover, the production of IL-6 was attenuated by CCN1 knockdown. Furthermore, we showed that CCN1 could activate IL-6 production via the PI3K/Akt/NF-κB signaling pathway by binding to α6β1 receptor. In summary, our results reveal a novel role of CCN1 in promoting inflammation by upregulation of IL-6 production in AIH. Our study also suggests that targeting of CCN1 may represent a novel strategy in AIH treatment. [ABSTRACT FROM AUTHOR]