Conservation of Ca2+/calmodulin regulation across Na and Ca2+ channels.

Voltage-gated Na and Ca2+ channels comprise distinct ion channel superfamilies, yet the carboxy tails of these channels exhibit high homology, hinting at a long-shared and purposeful module. For different Ca2+ channels, carboxyl-tail interactions with calmodulin do elaborate robust and similar forms of Ca2+ regulation. However, Na channels have only shown subtler Ca2+ modulation that differs among reports, challenging attempts at unified understanding. Here, by rapid Ca2+ photorelease onto Na channels, we reset this view of Na channel regulation. For cardiac-muscle channels (NaV1.5), reported effects from which most mechanistic proposals derive, we observe no Ca2+ modulation. Conversely, for skeletal-muscle channels (NaV1.4), we uncover fast Ca2+ regulation eerily similar to that of Ca2+ channels. Channelopathic myotonia mutations halve NaV1.4 Ca2+ regulation, and transplanting the NaV1.4 carboxy tail onto Ca2+ channels recapitulates Ca2+ regulation. Thus, we argue for the persistence and physiological relevance of an ancient Ca2+ regulatory module across Na and Ca2+ channels.

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study.

BACKGROUND: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. METHODS: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. RESULTS: We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26-6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06-6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67-4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. CONCLUSIONS: These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors.

Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti-PD-1-Based Immunotherapy as Curative-Intent Treatment.

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.

Application of exponential smoothing method and SARIMA model in predicting the number of admissions in a third-class hospital in Zhejiang Province.

OBJECTIVE: To establish the exponential smoothing prediction model and SARIMA model to predict the number of inpatients in a third-class hospital in Zhejiang Province, and evaluate the prediction effect of the two models, and select the best number prediction model. METHODS: The data of hospital admissions from January 2019 to September 2022 were selected to establish the exponential smoothing prediction model and the SARIMA model respectively. Then compare the fitting parameters of different models: R2_adjusted, R2, Root Mean Square Error (RMSE)、Mean Absolute Percentage Error (MAPE)、Mean Absolute Error(MAE) and standardized BIC to select the best model. Finally, the established model was used to predict the number of hospital admissions from October to December 2022, and the prediction effect of the average relative error judgment model was compared. RESULTS: The best fitting exponential smoothing prediction model was Winters Addition model, whose R2_adjusted was 0.533, R2 was 0.817, MAPE was 6.133, MAE was 447.341. The best SARIMA model is SARIMA(2,2,2)(0,1,1)12 model, whose R2_adjusted is 0.449, R2 is 0.199, MAPE is 8.240, MAE is 718.965. The Winters addition model and SARIMA(2,2,2)(0,1,1)12 model were used to predict the number of hospital admissions in October-December 2022, respectively. The results showed that the average relative error was 0.038 and 0.015, respectively. The SARIMA(2,2,2)(0,1,1)12 model had a good prediction effect. CONCLUSION: Both models can better fit the number of admissions, and SARIMA model has better prediction effect.

Update on Familial Adenomatous Polyposis-Associated Desmoid Tumors.

Desmoid tumors (DT) represent the second high risk of tumor in familial adenomatous polyposis (FAP) patients. Although FAP-associated DTs (FAP-DT) are caused by germline mutations in the adenomatous polyposis coli (APC) gene, extracolonic manifestations, sex, family history, genotype, and the ileal pouch anal anastomosis procedure are all linked to the development of DTs in FAP patients. Multidisciplinary management has replaced aggressive surgery as the preferred treatment of DTs. There is growing evidence to support the use of active surveillance strategy as first-line treatment for FAP-DT patients. Radiotherapy for intra-abdominal desmoids is now rarely used because of severe late toxicity. Pharmacotherapy, however, represents a promising future with the improvement of traditional cytotoxic drugs and the investigation of targeted drugs. Although nonsurgery treatment has been used widely nowadays, surgery remains the mainstay when symptomatic or life-threatening DTs are present. Further research will be needed for more optimal clinical practice.

St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

Surgery combined with photodynamic therapy versus surgery alone for the treatment of non-melanoma skin cancer and actinic keratosis: A retrospective cohort study.

Photodynamic therapy (PDT) is an effective treatment for some non-melanoma skin cancers (NMSC) and actinic keratosis. To compare recurrence-free survival (RFS) rates between surgery alone and surgery with postoperative PDT in patients with NMSC in China. This retrospective cohort study included patients with pathologically confirmed NMSC or actinic keratosis treated by surgical excision with/without PDT. A total of 125 patients were included, including 72 patients (43 females) aged 57-75 years in the surgery alone group and 53 patients (32 females) aged 61-76 years in the surgery+PDT group. The most common NMSC types were squamous cell carcinoma and basal cell carcinoma, the most common lesion site was the head and neck, and the vast majority of patients had a primary disease and solitary lesions. There were no significant differences between groups in baseline characteristics. RFS rates in the surgery alone and surgery+PDT groups were, respectively, 100.0% and 98.1% at 1 week, 98.6% and 98.1% at 4 weeks, 97.2% and 98.1% at 8 weeks, 97.2% and 98.1% at 12 weeks, and 90.3% and 90.4% at 24 weeks, with no significant differences between groups. Adjuvant PDT after surgical excision of NMSC or actinic keratosis does not provide short-term improvement in RFS, but the results need to be confirmed by a formal randomized controlled trial.

Associations of combined exposures to ambient temperature, air pollution, and green space with hypertension in rural areas of Anhui Province, China: A cross-sectional study.

Hypertension (HTN) was a major preventable cause of cardiovascular disease (CVD), contributing to a huge disease burden. Ambient temperature, air pollution and green space were important influencing factors of HTN, and few studies have assessed the effects and interactions of ambient temperature, air pollution and green space on HTN in rural areas. In this study, we selected 8400 individuals randomly in rural areas of Anhui Province by a multi-stage stratified cluster sampling. A total of 8383 individuals were included in the final analysis. We collected particulate pollutants and meteorological data from the local air quality monitoring stations and National Center for Meteorological Science from January 1 to December 31, 2020, respectively. The normalized differential vegetation index (NDVI) of Anhui Province in 2020 was produced and processed by remote sensing inversion on the basis of medium resolution satellite images. The average annual mean exposure concentrations of air pollution, meteorological factors, and NDVI were calculated for each individual based on the geocoded residential address. HTN was defined according the Chinese Guidelines for Prevention and Treatment of HTN. The effects and interactions of ambient temperature, air pollution and green space on HTN were evaluated by generalized linear model and interaction model, respectively. In this study, the prevalence of HTN was 24.14%. The adjusted odd ratio of HTN for each 1 µg/m3 increasing in PM2.5 and PM10, 1 °C of ambient temperature, and 0.1 of NDVI were:1.276 (1.013, 1.043), 1.012 (1.006, 1.018), 0.862 (0.862, 0.981) and 0.669 (0.611, 0.733), respectively. The results showed that air pollutants were positively correlated with HTN, while ambient temperature and green space were negatively correlated with HTN. Meanwhile, the negative associations of green space on HTN could decrease with the increasing concentrations of air pollution, but increase with the rising of ambient temperature.

Associations between essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid cancer.

Aim of this study was to evaluate the association between multiple essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid carcinoma (PTC). The concentrations of 10 essential microelements in urine [cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), strontium (Sr), zinc (Zn), and iodine (I)] were measured in 608 patients newly diagnosed with PTC, including 154 males and 454 females. Chi square test and Wilcoxon rank sum test were used to compare general characteristics among males and females. Multivariate logistic regression was used to evaluate the associations between essential microelements and PTC clinicopathologic characteristics in single- and multi-microelement models. In this study, we only observed that the frequency of lymph node metastasis in males was higher than in females, and males had higher levels of zinc than females, but males had lower levels of iodine than females. It was found that high levels of Fe were associated with decreased risk of PTC tumor size > 1 cm, capsular invasion, and advanced T stage (T3/4a/4b). High levels of Co and Mo were associated with decreased risk of capsular invasion and lymph node metastasis, respectively. However, high levels of Mn and Sr were associated with increased risk of capsular invasion and multifocality respectively, and both were associated with increased risk of advanced T stage (T3/4a/4b). These findings indicated that certain essential microelements might have potential effects on PTC progression and aggressiveness. Further studies are required to confirm these findings.

A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long-QT Syndrome.

RATIONALE: Calmodulinopathies comprise a new category of potentially life-threatening genetic arrhythmia syndromes capable of producing severe long-QT syndrome (LQTS) with mutations involving CALM1, CALM2, or CALM3. The underlying basis of this form of LQTS is a disruption of Ca2+/calmodulin (CaM)-dependent inactivation of L-type Ca2+ channels. OBJECTIVE: To gain insight into the mechanistic underpinnings of calmodulinopathies and devise new therapeutic strategies for the treatment of this form of LQTS. METHODS AND RESULTS: We generated and characterized the functional properties of induced pluripotent stem cell-derived cardiomyocytes from a patient with D130G-CALM2-mediated LQTS, thus creating a platform with which to devise and test novel therapeutic strategies. The patient-derived induced pluripotent stem cell-derived cardiomyocytes display (1) significantly prolonged action potentials, (2) disrupted Ca2+ cycling properties, and (3) diminished Ca2+/CaM-dependent inactivation of L-type Ca2+ channels. Next, taking advantage of the fact that calmodulinopathy patients harbor a mutation in only 1 of 6 redundant CaM-encoding alleles, we devised a strategy using CRISPR interference to selectively suppress the mutant gene while sparing the wild-type counterparts. Indeed, suppression of CALM2 expression produced a functional rescue in induced pluripotent stem cell-derived cardiomyocytes with D130G-CALM2, as shown by the normalization of action potential duration and Ca2+/CaM-dependent inactivation after treatment. Moreover, CRISPR interference can be designed to achieve selective knockdown of any of the 3 CALM genes, making it a generalizable therapeutic strategy for any calmodulinopathy. CONCLUSIONS: Overall, this therapeutic strategy holds great promise for calmodulinopathy patients as it represents a generalizable intervention capable of specifically altering CaM expression and potentially attenuating LQTS-triggered cardiac events, thus initiating a path toward precision medicine.

Effective NaBH4-exfoliated ultrathin multilayer Co(OH)2 nanosheets arrays and sulfidation for energy storage.

Facile engineering ultrathin nano structural materials is still a huge challenge for material science. Thereinto, the strategy of exfoliating shows great advantages. In this work, we develop a convenient approach to exfoliate Co(OH)2 nanosheets into ultrathin Co(OH)2 nanoflakes through NaBH4-exfoliation method. Moreover, the microstructures of the Co(OH)2 nanosheets are conveniently controlled by varying the exfoliation time. As a result, the obtained ultrathin Co(OH)2-72 h nanosheets deliver the excellent electrochemical performance. In order to improve the energy storage properties, the obtained ultrathin Co(OH)2 nanosheets are further modified to enhance the conductivity via sulfidation. Consequently, the synthesized Co(OH)2-72 h/CoS2 composites exhibit a specific capacitance of 2536 F g-1 at 1 A g-1, which is more outstanding than that of Co(OH)2-72 h. What's more, the Co(OH)2-72 h/CoS2 composites show a capacitance retention of 83.3% after 10 000 cycles. Besides, the assembled asymmetric supercapacitor displays a power density of 482 W kg-1 at an energy density of 36 Wh kg-1, demonstrating a large potential for application.

Enzyme-inhibitor-like tuning of Ca(2+) channel connectivity with calmodulin.

Ca(2+) channels and calmodulin (CaM) are two prominent signalling hubs that synergistically affect functions as diverse as cardiac excitability, synaptic plasticity and gene transcription. It is therefore fitting that these hubs are in some sense coordinated, as the opening of Ca(V)1-2 Ca(2+) channels are regulated by a single CaM constitutively complexed with channels. The Ca(2+)-free form of CaM (apoCaM) is already pre-associated with the isoleucine-glutamine (IQ) domain on the channel carboxy terminus, and subsequent Ca(2+) binding to this 'resident' CaM drives conformational changes that then trigger regulation of channel opening. Another potential avenue for channel-CaM coordination could arise from the absence of Ca(2+) regulation in channels lacking a pre-associated CaM. Natural fluctuations in CaM concentrations might then influence the fraction of regulable channels and, thereby, the overall strength of Ca(2+) feedback. However, the prevailing view has been that the ultrastrong affinity of channels for apoCaM ensures their saturation with CaM, yielding a significant form of concentration independence between Ca(2+) channels and CaM. Here we show that significant exceptions to this autonomy exist, by combining electrophysiology (to characterize channel regulation) with optical fluorescence resonance energy transfer (FRET) sensor determination of free-apoCaM concentration in live cells. This approach translates quantitative CaM biochemistry from the traditional test-tube context into the realm of functioning holochannels within intact cells. From this perspective, we find that long splice forms of Ca(V)1.3 and Ca(V)1.4 channels include a distal carboxy tail that resembles an enzyme competitive inhibitor that retunes channel affinity for apoCaM such that natural CaM variations affect the strength of Ca(2+) feedback modulation. Given the ubiquity of these channels, the connection between ambient CaM levels and Ca(2+) entry through channels is broadly significant for Ca(2+) homeostasis. Strategies such as ours promise key advances for the in situ analysis of signalling molecules resistant to in vitro reconstitution, such as Ca(2+) channels.

Novel fluorescence resonance energy transfer-based reporter reveals differential calcineurin activation in neonatal and adult cardiomyocytes.

Novel fluorescence resonance energy transfer-based genetically encoded reporters of calcineurin are constructed by fusing the two subunits of calcineurin with P2A-based linkers retaining the expected native conformation of calcineurin. Calcineurin reporters display robust responses to calcium transients in HEK293 cells. The sensor responses are correlated with NFATc1 translocation dynamics in HEK293 cells. The sensors are uniformly distributed in neonatal myocytes and respond efficiently to single electrically evoked calcium transients and show cumulative activation at frequencies of 0.5 and 1 Hz. In adult myocytes, the calcineurin sensors appear to be localized to the cardiac z-lines, and respond to cumulative calcium transients at frequencies of 0.5 and 1 Hz. The phosphatase calcineurin is a central component of many calcium signalling pathways, relaying calcium signals from the plasma membrane to the nucleus. It has critical functions in a multitude of systems, including immune, cardiac and neuronal. Given the widespread importance of calcineurin in both normal and pathological conditions, new tools that elucidate the spatiotemporal dynamics of calcineurin activity would be invaluable. Here we develop two separate genetically encoded fluorescence resonance energy transfer (FRET)-based sensors of calcineurin activation, DuoCaN and UniCaN. Both sensors showcase a large dynamic range and rapid response kinetics, differing primarily in the linker structure between the FRET pairs. Both sensors were calibrated in HEK293 cells and their responses correlated well with NFAT translocation to the nucleus, validating the biological relevance of the sensor readout. The sensors were subsequently expressed in neonatal rat ventricular myocytes and acutely isolated adult guinea pig ventricular myocytes. Both sensors demonstrated robust responses in myocytes and revealed kinetic differences in calcineurin activation during changes in pacing rate for neonatal versus adult myocytes. Finally, mathematical modelling combined with quantitative FRET measurements provided novel insights into the kinetics and integration of calcineurin activation in response to myocyte Ca transients. In all, DuoCaN and UniCaN stand as valuable new tools for understanding the role of calcineurin in normal and pathological signalling.

A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels.

Ca2+/calmodulin-dependent regulation of voltage-gated CaV1-2 Ca2+ channels shows extraordinary modes of spatial Ca2+ decoding and channel modulation, vital for many biological functions. A single calmodulin (CaM) molecule associates constitutively with the channel's carboxy-terminal tail, and Ca2+ binding to the C-terminal and N-terminal lobes of CaM can each induce distinct channel regulations. As expected from close channel proximity, the C-lobe responds to the roughly 100-microM Ca2+ pulses driven by the associated channel, a behaviour defined as 'local Ca2+ selectivity'. Conversely, all previous observations have indicated that the N-lobe somehow senses the far weaker signals from distant Ca2+ sources. This 'global Ca2+ selectivity' satisfies a general signalling requirement, enabling a resident molecule to remotely sense cellular Ca2+ activity, which would otherwise be overshadowed by Ca2+ entry through the host channel. Here we show that the spatial Ca2+ selectivity of N-lobe CaM regulation is not invariably global but can be switched by a novel Ca2+/CaM-binding site within the amino terminus of channels (NSCaTE, for N-terminal spatial Ca2+ transforming element). Native CaV2.2 channels lack this element and show N-lobe regulation with a global selectivity. On the introduction of NSCaTE into these channels, spatial Ca2+ selectivity transforms from a global to local profile. Given this effect, we examined CaV1.2/CaV1.3 channels, which naturally contain NSCaTE, and found that their N-lobe selectivity is indeed local. Disruption of this element produces a global selectivity, confirming the native function of NSCaTE. Thus, differences in spatial selectivity between advanced CaV1 and CaV2 channel isoforms are explained by the presence or absence of NSCaTE. Beyond functional effects, the position of NSCaTE on the channel's amino terminus indicates that CaM can bridge the amino terminus and carboxy terminus of channels. Finally, the modularity of NSCaTE offers practical means for understanding the basis of global Ca2+ selectivity.

Green roof development knowledge map: A review of visual analysis using CiteSpace and VOSviewer.

Green roofs are generally acknowledged as environmentally sustainable roof systems with several environmental, economic, and social benefits, as well as an effective and practical strategy for mitigating the negative consequences of urbanization. In this paper, we used CiteSpace and VOSviewer bibliometric software for visual analysis, citation analysis, co-authorship network, co-citation analysis, and keyword analysis for descriptive statistics on 3986 articles on "green roofs" published in the Web of Science core database since 2000. Descriptive statistics were used for citation analysis, co-authorship network, co-citation analysis, and keyword analysis. According to a review of green roofing-related research literature, (1) Through analysis from three dimensions of country, institution, and author, it was found that China, the United States, and Italy ranked among the top three countries in terms of green roof publication volume; All but three of the top 10 institutions in terms of publications are from China and all are from developed countries; A large-scale collaborative network has not yet formed among authors. (2) Through keyword clustering analysis, it was found that "green roof," "performance," and "UHI" were the three keywords with the highest frequency. The research direction of this theme mainly includes five primary themes: rainwater management, urban biodiversity, building energy efficiency, alleviating urban heat islands and improving air quality, sustainable development, and public health. Through keyword hot words, it is found that the frequency of occurrence is relatively high, mainly involving energy conservation, alleviating urban heat islands, biodiversity, and sustainable development. The research on sustainable development, its impact on urban microclimate, and air quality remains a hot topic through keyword highlighting. (3) Co-citation analysis was used to identify the most influential journals, highly cited publications, and authors. (4) Three potential study objectives have been identified: synergistic development with other green infrastructures from an urban planning standpoint, localized research on green roofs, and photovoltaic green roofs.

Application of problem based learning (PBL) and case based learning (CBL) in the teaching of international classification of diseases encoding.

To study the application of PBL combined with CBL teaching mode in the teaching of international classification of diseases (ICD) encoding, so as to improve students' grasp of ICD encoding knowledge. From March 2020 to June 2020, 50 students majoring in health information management who were interns in a Grade A general hospital were selected as the research participants and randomly divided into experimental group and control group, 25 in each group. The experimental group and the control group adopted the PBL combined CBL teaching mode and the traditional teaching mode respectively to carry out the classification and coding teaching. The academic achievement of the two groups of students was evaluated by means of achievement assessment and questionnaire survey based on information processing theory. The scores of theoretical knowledge in the experimental group and the control group were 79.78 ± 8.55 and 70.92 ± 10.81, respectively, and the scores of skill operation in the two groups were 79.76 ± 8.28 and 70.00 ± 10.41, respectively. The test scores of the experimental group were higher than those of the control group, and the difference was statistically significant (P < 0.05). The scores of knowledge acquisition ability of experimental group and control group were 16.72 ± 1.79 and 16.60 ± 2.36, the scores of knowledge sharing ability were 24.20 ± 2.61 and 21.00 ± 2.65, the scores of knowledge storage ability were 20.80 ± 2.47 and 17.24 ± 4.90, respectively. The scores of knowledge application ability were 14.00 ± 1.80 and 11.00 ± 2.69, the scores of knowledge innovation ability were 20.16 ± 2.34 and 18.08 ± 3.70, and the total scores were 95.88 ± 6.08 and 83.92 ± 11.30, respectively. The scores of all questionnaires in the experimental group were higher than those in the control group. The scores of knowledge sharing ability, knowledge storage ability, knowledge application ability, knowledge innovation ability and total score between the two groups were higher than those of the control group, and the differences were statistically significant (P < 0.05). PBL combined with CBL teaching model has good academic achievement in ICD encoding teaching, which can significantly improve academic performance and learning ability, and is worthy of promotion.

The role and application of fibroblast activating protein.

Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is rarely expressed in normal tissues but highly abundant in pathological diseases, including fibrosis, arthritis, and cancer. Ever since its discovery, we have deciphered its structure and biological properties and continue to investigate its roles in various diseases while attempting to utilize it for targeted therapy. To date, no significant breakthroughs have been made in terms of efficacy. However, in recent years, several practical applications in the realm of imaging diagnosis have been discovered. Given its unique expression in a diverse array of pathological tissues, the fundamental biological characteristics of FAP render it a crucial target for disease diagnosis and immunotherapy. To obtain a more comprehensive understanding of the research progress of FAP, its biological characteristics, involvement in diseases, and recent targeted application research have been reviewed. Moreover, we explored its development trend in the direction of clinical diagnoses and treatment.

Growth Differentiation Factor-15 Predicts Mortality and Heart Failure Exacerbation But Not Ventricular Arrhythmias in Patients With Cardiomyopathy.

Background Heart failure (HF) has been increasing in prevalence, and a need exists for biomarkers with improved predictive and prognostic ability. GDF-15 (growth differentiation factor-15) is a novel biomarker associated with HF mortality, but no serial studies of GDF-15 have been conducted. This study aimed to investigate the association between GDF-15 levels over time and the occurrence of ventricular arrhythmias, HF hospitalizations, and all-cause mortality. Methods and Results We used a retrospective case-control design to analyze 148 patients with ischemic and nonischemic cardiomyopathies and primary prevention implantable cardioverter-defibrillator (ICD) from the PROSe-ICD (Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention) cohort. Patients had blood drawn every 6 months and after each appropriate ICD therapy and were followed for a median follow-up of 4.6 years, between 2005 to 2019. We compared serum GDF-15 levels within ±90 days of an event among those with a ventricular tachycardia/fibrillation event requiring ICD therapies and those hospitalized for decompensated HF. A comparator/control group comprised patients with GDF-15 levels available during 2-year follow-up periods without events. Median follow-up was 4.6 years in the 148 patients studied (mean age 58±12, 27% women). The HF cohort had greater median GDF-15 values within 90 days (1797 pg/mL) and 30 days (2039 pg/mL) compared with the control group (1062 pg/mL, both P<0.0001). No difference was found between the ventricular tachycardia/fibrillation subgroup within 90 days (1173 pg/mL, P=0.60) or 30 days (1173 pg/mL, P=0.78) and the control group. GDF-15 was also significantly predictive of mortality (hazard ratio, 3.17 [95% CI, 2.33-4.30]). Conclusions GDF-15 levels are associated with HF hospitalization and mortality but not ventricular arrhythmic events.

Efficacy of PD-1 inhibitors for colorectal cancer and polyps in Lynch syndrome patients.

BACKGROUND: Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients. METHODS: LS patients with CRC who had evaluable tumours and received at least 2 cycles of PD-1 inhibitors were retrospectively included. PD-1 inhibitors were given as a monotherapy or in combination with other therapies, including anticytotoxic T-lymphocyte-associated antigen-4 treatment, radiotherapy, chemotherapy, and targeted therapy. Correlations of treatment responses with clinicopathological characteristics and genomic profiles were analysed. RESULTS: A total of 75 LS patients were included, with a median age of 39 years. The median duration of follow-up was 27 months (range, 3-71). The objective response rate (ORR) was 70.7%, including 28.0% (n = 21) complete responses and 42.7% (n = 32) partial responses. Four of five cases of LS CRCs displaying proficient MMR (pMMR) or microsatellite stable (MSS) were not responsive. Mucinous/signet-ring cell differentiation was associated with a lower ORR (P = 0.013). The 3-year overall survival and progression-free survival were 91.2% and 82.2%, respectively. A polyp was detected in 26 patients during surveillance. Seven adenomas disappeared after treatment, and they were all larger than 7 mm. CONCLUSION: PD-1 inhibitors are highly effective for dMMR and MSI-H LS CRCs, but not for pMMR or MSS LS CRCs or mucinous/signet-ring cell CRC. Large LS adenomas may also be eliminated by anti-PD-1 treatment. DATA AVAILABILITY STATEMENT: Due to the privacy of patients, the related data cannot be available for public access but can be obtained from Pei-Rong Ding (dingpr@sysucc.org.cn) upon reasonable request. The key raw data have been uploaded to the Research Data Deposit public platform (www.researchdata.org.cn).

Quality evaluation of Semen Cassiae (Cassia obtusifolia L.) by using ultra-high performance liquid chromatography coupled with mass spectrometry.

A sensitive and reliable ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry has been developed and partially validated to evaluate the quality of Semen Cassiae (Cassia obtusifolia L.) through simultaneous determination of 11 anthraquinones and two naphtha-γ-pyrone compounds. The analysis was achieved on a Poroshell 120 EC-C(18) column (100 mm × 2.1 mm, 2.7 µm; Agilent, Palo Alto, CA, USA) with gradient elution using a mobile phase that consisted of acetonitrile-water (30 mM ammonium acetate) at a flow rate of 0.4 mL/min. For quantitative analysis, all calibration curves showed perfect linear regression (r(2) > 0.99) within the testing range. This method was also validated with respect to precision and accuracy, and was successfully applied to quantify the 13 components in nine batches of Semen Cassiae samples from different areas. The performance of developed method was compared with that of conventional high-performance liquid chromatography method. The significant advantages of the former include high-speed chromatographic separation, four times faster than high-performance liquid chromatography with conventional columns, and great enhancement in sensitivity. This developed method provided a new basis for overall assessment on quality of Semen Cassiae.