Home-based mobile-guided exercise-based cardiac rehabilitation among patients undergoing transcatheter aortic valve replacement (REHAB-TAVR): protocol for a randomised clinical trial.

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) is a standard treatment for aortic stenosis, particularly in older adults. Reduced exercise capacity and frailty significantly impact outcomes in TAVR patients, yet current management lacks strategies to address these issues. This study aims to assess the effectiveness of home-based mobile-guided exercise-based cardiac rehabilitation in TAVR patients, led by a multidisciplinary team with clear progression milestones. METHODS AND ANALYSIS: The study involves 90 patients aged 60-89 in a single centre who will be randomised to a 3-month novel multidomain exercise intervention or routine care. Outcome assessors will be blinded towards group allocation. The primary outcome is the 6-min walk distance at month 3. The secondary outcomes include the 6-min walk distance at month 6, physical function measured by total Short Physical Performance Battery score and exercise adherence measured by the Exercise Adherence Rating Scale at months 3 and 6. Additional outcome measures, including rehospitalisations, death, handgrip strength, frailty (Fried Criteria and Essential Toolset), cognitive function (Mini-Mental State Examination), quality of life (EuroQol 5-Dimension 5-Level), nutritional status (Mini-Nutritional Assessment), anxiety (General Anxiety Disorder-7), depression (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), functional capacity (Duke Activity Status Index), clinical indices (body mass index, symptoms, signs, left ventricular ejection fraction (LVEF), N-Terminal Pro-Brain Natriuretic Peptide, etc) and social support (Lubben Social Network Scale-6), along with comprehensive cost analysis, enhance the study's significance. The study's findings hold crucial implications for crafting an effective exercise-focused cardiac rehabilitation strategy for TAVR patients. Community implementation not only deepens understanding but also fosters the potential integration of exercise-based cardiac rehabilitation into self-care, promising enhanced patient adherence and overall cardiovascular health management. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Zhongshan Hospital, Fudan University Ethics Committee (B2022-062R). Results will be disseminated to local stakeholders and the research community through publications and conferences. TRIAL REGISTRATION NUMBER: NCT05989594.

Preparation of copper nanoparticles fluorescent probes and detection of hydrogen peroxide and glucose.

Fluorescent copper nanoparticles (CuNPs) was synthesized by one-step chemical reduction method using ascorbic acid (AA) and copper sulfate (CuSO4⋅5H2O) as raw materials, which had good water solubility and fluorescence properties. A green, simple and safe CuNPs@Fe2+ fluorescence probe was developed for the detection of hydrogen peroxide and glucose using Fe2+ as a bridge. The prepared CuNPs could obtain the maximum fluorescence emission wavelength at 440 nm when the excitation wavelength was 360 nm. The average particle size of CuNPs was 10 nm, which had good photobleach resistance, stability and salt tolerance. The fluorescence intensity was quenched due to electron transfer (ET) process when hydrogen peroxide was added to CuNPs@Fe2+ system. This result was mainly because Fenton reaction occured between hydrogen peroxide and Fe2+, producing hydroxyl free radicals (OH) and Fe3+. Since glucose could be catalyzed by specific glucose oxidase (GOX) to produce H2O2 and corresponding oxidation products, the quantitative analysis of glucose was realized when glucose oxidase was introduced into the CuNPs@Fe2+ sensor system. Therefore, a novel CuNPs@Fe2+ fluorescent probe sensor study was constructed to further achieve quantitative detection of H2O2 and glucose. Under the optimized experimental conditions, the linear ranges for H2O2 and glucose were 28.219-171.562 µM and 1.237-75.771 µM, respectively. And the detection limits for H2O2 and glucose were 7.169 µM and 0.540 µM, respectively. In addition, the mechanism of fluorescence probe quenching caused by the interaction between H2O2 and CuNPs@Fe2+ was also discussed. The proposed sensing system had been applied successfully to the detection of glucose in human serum samples.

Effect fraction of Bletilla striata (Thunb.) Reichb.f. alleviates LPS-induced acute lung injury by inhibiting p47phox/NOX2 and promoting the Nrf2/HO-1 signaling pathway.

BACKGROUND & AIMS: The effect fraction of Bletilla striata (Thunb.) Reichb.f. (EFBS), a phenolic-rich extract, has significant protective effects on lipopolysaccharide (LPS)-induced acute lung injury (ALI), but its composition and molecular mechanisms are unclear. This study elucidated its chemical composition and possible protective mechanisms against LPS-induced ALI from an antioxidant perspective. METHODS: EFBS was prepared by ethanol extraction, enriched by polyamide column chromatography, and characterized using ultra-performance liquid chromatography/time-of-flight mass spectrometry. The LPS-induced ALI model and the RAW264.7 model were used to evaluate the regulatory effects of EFBS on oxidative stress, and transcriptome analysis was performed to explore its possible molecular mechanism. Then, the pathway by which EFBS regulates oxidative stress was validated through inhibitor intervention, flow cytometry, quantitative PCR, western blotting, and immunofluorescence techniques. RESULTS: A total of 22 compounds in EFBS were identified. The transcriptome analyses of RAW264.7 cells indicated that EFBS might reduce reactive oxygen species (ROS) production by inhibiting the p47phox/NADPH oxidase 2 (NOX2) pathway and upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Both in vitro and in vivo data confirmed that EFBS significantly inhibited the expression and phosphorylation of p47phox protein, thereby weakening the p47phox/NOX2 pathway and reducing ROS production. EFBS significantly increased the expression of Nrf2 in primary peritoneal macrophages and lung tissue and promoted its nuclear translocation, dose-dependent increase in HO-1 levels, and enhancement of antioxidant activity. In vitro, both Nrf2 and HO-1 inhibitors significantly reduced the scavenging effects of EFBS on ROS, further confirming that EFBS exerts antioxidant effects at least partially by upregulating the Nrf2/HO-1 pathway. CONCLUSIONS: EFBS contains abundant phenanthrenes and dibenzyl polyphenols, which can reduce ROS production by inhibiting the p47phox/NOX2 pathway and enhance ROS clearance activity by upregulating the Nrf2/HO-1 pathway, thereby exerting regulatory effects on oxidative stress and improving LPS-induced ALI.

A signal-switchable fluorescent probe for detection of HPO4 2- based on 5,10,15,20-(4-sulphonatophenyl)porphyrin (TPPS4 ).

In this study, 5,10,15,20-(4-sulphonatophenyl)porphyrin (TPPS4 ) was selected as a fluorescent probe due to its excellent characteristics including high quantum yield, good water solubility, and exceptional biocompatibility. With an excitation wavelength set at 515 nm, the optimal fluorescence emission wavelength for TPPS4 was measured at 642 nm. At this moment, the fluorescence signal of TPPS4 pink solution was in the 'ON' state. The fluorescence intensity of TPPS4 was quenched when ascorbic acid (AA) was introduced, which was due to the electron transfer quenching effect between AA and TPPS4 . The colour of the corresponding solution changed from pink to green, and the fluorescence signal was in the 'OFF' state. When HPO4 2- was further introduced into the TPPS4 -AA system, the quenched fluorescence intensity of TPPS4 was recovered due to the unique interaction between HPO4 2- and AA. At this time, the colour of the corresponding solution changed from green to red, and the fluorescence signal was in the 'ON' state. Therefore, an 'ON-OFF-ON' signal-switchable fluorescent probe was constructed based on TPPS4 to detect HPO4 2- . The results showed that the linear range of HPO4 2- was 4.0 × 10-9 to 1.7 × 10-6  M, and the detection limit was 1.3 × 10-9  M (S/N = 3). The sensing system exhibited high accuracy and sensitivity, and it could be used successfully to detect HPO4 2- in real samples.

Novel "on-off" fluorescence sensing for rapid and accurate determination of Cr3+ based on g-CNQDs.

Cr3+ is one of the most essential trace elements in living organisms and plays a vital role in human metabolism. However, both deficiency and excess intake of Cr3+ can be harmful to the human body. Therefore, the quantitative determination of Cr3+ is of great significance in the field of life science. Based on this, in this study, a g-CNQDs@p-acetaminophenol fluorescence sensing system was developed for the quantitative detection of Cr3+ in actual complex samples. G-CNQDs were synthesized with sodium citrate and urea as precursors. The fluorescence signal was enhanced by the synergistic effect between p-acetaminophenol (APAP) and g-CNQDs. The fluorescence quenching phenomenon can be produced when Cr3+ is introduced into the fluorescence-enhanced g-CNQDs@p-acetaminophenol system. An "on-off" fluorescence sensing system was constructed based on g-CNQDs@p-acetaminophenol for the quantitative detection of Cr3+. The experimental data showed a wide linear region in the concentration range of 0.64-63.0 µM, and the detection limit was as low as 0.23 µM. The construction of the sensor system broadens the research field for the practical application of Cr3+.

Progress in the treatment of drug-loaded nanomaterials in renal cell carcinoma.

Renal cell carcinoma (RCC) is a common urinary tract tumor that arises from the highly heterogeneous epithelium of the renal tubules. The incidence of kidney cancer is second only to the incidence of bladder cancer, and has shown an upward trend over time. Although surgery is the preferred treatment for localized RCC, treatment decisions should be customized to individual patients considering their overall health status and the risk of developing or worsening chronic kidney disease postoperatively. Anticancer drugs are preferred to prevent perioperative and long-term postoperative complications; however, resistance to chemotherapy remains a considerable problem during the treatment process. To overcome this challenge, nanocarriers have emerged as a promising strategy for targeted drug delivery for cancer treatment. Nanocarriers can transport anticancer agents, achieving several-fold higher cytotoxic concentrations in tumors and minimizing toxicity to the remaining parts of the body. This article reviews the use of nanomaterials, such as liposomes, polymeric nanoparticles, nanocomposites, carbon nanomaterials, nanobubbles, nanomicelles, and mesoporous silica nanoparticles, for RCC treatment, and discusses their advantages and disadvantages.

Macrocyclization via remote meta-selective C-H olefination using a practical indolyl template.

The synthesis of macrocyclic compounds with different sizes and linkages remains a great challenge via transition metal-catalysed intramolecular C-H activation. Herein, we disclose an efficient macrocyclization strategy via Pd-catalysed remote meta-C-H olefination using a practical indolyl template. This approach was successfully employed to access macrolides and coumarins. In addition, the intermolecular meta-C-H olefination also worked well and was exemplified by the synthesis of antitumor drug belinostat from inexpensive and readily available benzenesulfonyl chloride. Notably, catalytic copper acetate and molecular oxygen were used in place of silver salts as oxidants. Furthermore, for the first time, the formation of a macrocyclophane cyclopalladated intermediate was detected through in situ Fourier-transform infrared monitoring experiments and ESI-MS.

Effectiveness of kumquat decoction for the improvement of cough caused by SARS-CoV-2 Omicron variants, a multicentre, prospective observational study.

BACKGROUND: Kumquat decoction is a traditional Chinese medicine formula and has been widely used to alleviate the coronavirus disease 2019 (COVID-19)-related cough in China. However, the effectiveness and safety of kumquat decoction remain unclear. PURPOSE: To assess the effectiveness and safety of kumquat decoction for COVID-19-related cough. STUDY DESIGN: A multicentre, prospective observational study. METHODS: We enrolled consecutive patients with mild-to-moderate COVID-19 from December 31, 2022, to January 3, 2023, during the Omicron phase in Yangshuo County, China. The primary outcome was the time from study baseline to sustained cough resolution by the last follow-up day on January 31, 2023. The effectiveness was evaluated by Cox proportional hazards models based on propensity score analyses. The secondary outcomes were the resolution of cough and other COVID-19-related symptoms by Days 3, 5, and 7. RESULTS: Of 1434 patients, 671 patients were excluded from the analysis of cough resolution. Among the remaining 763 patients, 481 (63.04%) received kumquat decoction, and 282 (36.96%) received usual care. The median age was 38.0 (interquartile range [IQR] 29.0, 50.0) years, and 55.7% were women. During a median follow-up of 7.000 days, 68.2% of patients in the kumquat group achieved sustained cough resolution (93.77 per 1000 person-days) compared to 39.7% in the usual care group (72.94 per 1000 person-days). The differences in restricted mean survival time (RMST) (kumquat decoction minus usual care group) for cough resolution were -0.742 days (95% CI, -1.235 to -0.250, P = 0.003) on Day 7. In the main analysis using propensity-score matching, the adjusted hazard ratio (HR) for cough resolution (kumquat decoction vs. usual care group) was 1.94 (95% CI, 1.48 to 2.53, P < 0.001). Similar findings were found in multiple sensitivity analyses. In addition, the use of kumquat decoction was associated with the resolution of cough, and a stuffy nose on Days 5 and 7, as well as the resolution of sore throat on Day 7 following medication. CONCLUSION: In this study among patients with COVID-19-related cough, receiving kumquat decoction was associated with an earlier resolution of cough symptoms.

New asymptomatic thrombosis caused by carotid web during the acute period of cerebral infarction.

BACKGROUND: At present, the carotid web (CaW) as an important cause of cryptogenic ischemic stroke has gradually received clinical attention. CaW is associated with a high risk of stroke and patient is more likely to have recurrent stroke if the CaW is untreated. We report a patient who developed CaW related thrombosis during the acute period of cerebral infarction. CASE PRESENTATION: A 49-year-old male patient with CaW in the left internal carotid artery was diagnosed by computed tomography angiography (CTA) and had two cerebral infarctions in two years. Within 72 h after thrombolysis for an acute cerebral infarction, acute thrombosis was identified between the web and the posterior wall of the carotid artery on carotid ultrasound. Emergent carotid endarterectomy (CEA) was performed to remove abnormal CaW structures and thrombosis to prevent stroke. The patient recovered well and was asymptomatic at 2 months follow-up. CONCLUSION: Carotid web related thromboembolism is a rare cause of stroke. Carotid ultrasound plays an important role in the diagnosis of asymptomatic thrombosis caused by carotid web. Carotid endarterectomy is effective for stroke prevention in patient with carotid web related thrombosis.

Baicalin suppress the development of polycystic ovary syndrome via regulating the miR-874-3p/FOXO3 and miR-144/FOXO1 axis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS. OBJECTIVE: This study determines whether baicalin could affect the progression of PCOS. MATERIALS AND METHODS: To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 µM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 µM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect. CONCLUSIONS: Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

Binary classification of non-specific low back pain condition based on the combination of B-mode ultrasound and shear wave elastography at multiple sites.

Introduction: Low back pain (LBP) is a prevalent and complex condition that poses significant medical, social, and economic burdens worldwide. The accurate and timely assessment and diagnosis of LBP, particularly non-specific LBP (NSLBP), are crucial to developing effective interventions and treatments for LBP patients. In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of NSLBP patients. Methods: We recruited 52 subjects with NSLBP from the University of Hong Kong-Shenzhen Hospital and collected B-mode ultrasound images and SWE data from multiple sites. The Visual Analogue Scale (VAS) was used as the ground truth to classify NSLBP patients. We extracted and selected features from the data and employed a support vector machine (SVM) model to classify NSLBP patients. The performance of the SVM model was evaluated using five-fold cross-validation and the accuracy, precision, and sensitivity were calculated. Results: We obtained an optimal feature set of 48 features, among which the SWE elasticity feature had the most significant contribution to the classification task. The SVM model achieved an accuracy, precision, and sensitivity of 0.85, 0.89, and 0.86, respectively, which were higher than the previously reported values of MRI. Discussion: In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of non-specific low back pain (NSLBP) patients. Our results showed that combining B-mode ultrasound image features with SWE features and employing an SVM model can improve the automatic classification of NSLBP patients. Our findings also suggest that the SWE elasticity feature is a crucial factor in classifying NSLBP patients, and the proposed method can identify the important site and position of the muscle in the NSLBP classification task.

Development of Binder-Free Pigment Inks for Direct Inkjet Printing on Cotton Fabric without Pretreatment.

Inkjet printing technology is widely used in the textile digital printing application today though the current technology still requires pretreatment and postwashing procedures before and after printing. Additional chemical treatment generates a large amount of wastewater and complicates the process. Among the many potential approaches for reducing chemical waste, pigments with self-dispersing capability were prepared and formulated into binder-free inkjet inks that require no pretreatment or after-washing process when printing cotton fabrics. The new self-dispersing pigment inks were tested and evaluated on cotton fabrics. The distribution of particles was between 122.2 and 188.5 nm, and inks have excellent storage capability. Printed fabrics' light fastness and acid/alkali resistance are about grade 5, and printed cotton's washing and rubbing fastness are above grade 3. The mechanism and performance of ink drops were investigated by LF-NMR and ink-drop observation methods. This work provides a possible solution for reducing wastewater in the textile industry.

Post-hospitalization rehabilitation alleviates long-term immune repertoire alteration in COVID-19 convalescent patients.

The global pandemic of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an once-in-a-lifetime public health crisis. Among hundreds of millions of people who have contracted with or are being infected with COVID-19, the question of whether COVID-19 infection may cause long-term health concern, even being completely recovered from the disease clinically, especially immune system damage, needs to be addressed. Here, we performed seven-chain adaptome immune repertoire analyses on convalescent COVID-19 patients who have been discharged from hospitals for at least 6 months. Surprisingly, we discovered lymphopenia, reduced number of unique CDR3s, and reduced diversity of the TCR/BCR immune repertoire in convalescent COVID-19 patients. In addition, the BCR repertoire appears to be activated, which is consistent with the protective antibody titres, but serological experiments reveal significantly lower IL-4 and IL-7 levels in convalescent patients compared to those in healthy controls. Finally, in comparison with convalescent patients who did not receive post-hospitalization rehabilitation, the convalescent patients who received post-hospitalization rehabilitation had attenuated immune repertoire abnormality, almost back to the level of healthy control, despite no detectable clinic demographic difference. Overall, we report the potential long-term immunological impairment for COVID-19 infection, and correction of this impairment via post-hospitalization rehabilitation may offer a new prospect for COVID-19 recovery strategy.

DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation.

Deletion of the conserved C-terminus of the Rothmund-Thomson syndrome helicase RECQ4 is highly tumorigenic. However, while the RECQ4 N-terminus is known to facilitate DNA replication initiation, the function of its C-terminus remains unclear. Using an unbiased proteomic approach, we identify an interaction between the RECQ4 N-terminus and the anaphase-promoting complex/cyclosome (APC/C) on human chromatin. We further show that this interaction stabilizes APC/C co-activator CDH1 and enhances APC/C-dependent degradation of the replication inhibitor Geminin, allowing replication factors to accumulate on chromatin. In contrast, the function is blocked by the RECQ4 C-terminus, which binds to protein inhibitors of APC/C. A cancer-prone, C-terminal-deleted RECQ4 mutation increases origin firing frequency, accelerates G1/S transition, and supports abnormally high DNA content. Our study reveals a role of the human RECQ4 C-terminus in antagonizing its N-terminus, thereby suppressing replication initiation, and this suppression is impaired by oncogenic mutations.

[Seasonal change of habitat selection of Hydropotes inermis in Yancheng coastal wetlands, China]. / ç›åŸŽæ»¨æµ·æ¹¿åœ°çæ –æ¯åœ°é€‰æ‹©çš„å­£èŠ‚å˜åŒ–.

Yancheng coastal wetlands are one of the main habitats and breeding grounds of wild Chinese water deer (Hydropotes inermis). Based on GPS-GSM tracking data, we used the habitat selection index and MaxEnt model to simulate and analyze the distribution of suitable habitat of H. inermis in different seasons as well as the main influencing factors. The results showed that H. inermis mainly used reed marshes, with the usage rate in spring-summer and autumn-winter being 52.7% and 62.8%, respectively. The area under receiver operating characteristic curve value simulated by MaxEnt model in different seasons was 0.873 and 0.944, which showed high prediction accu-racy. In spring and summer, the sub-suitable and most suitable habitats were mainly reed marshes, farmland, and ponds. In autumn and winter, the main habitat types were reed marshes and ponds, with an area equivalent to only 5.7% and 8.5% of that in spring and summer. Distance to reeds, distance to Spartina alterniflora, habitat types, distance to water and distance residential area were the main environmental variables affecting the distribution of H. inermis in spring and summer. The above five variables and vegetation height were the main environmental variables affecting the distribution of H. inermis in autumn and winter. This study would provide an important reference for the conservation of Chinese water deer and the fine management of their habitats in Yancheng coastal wetlands.

Modification of Hollow Expanded Microspheres with Superior Thermal Insulation Properties and Their Applications.

Thermally expandable microspheres (TEMs) are hollow polymeric particles in which a blowing gas has been encapsulated. This property makes them excellent for thermal insulation applications, such as lightweight fillers. This study has developed a viable technology for further improving thermal insulation properties in the field that needs excellent thermal insulation of textile fabrics. The ATO/TEMs composites were designed and prepared to reduce sunlight radiation by the charge gravity method. The test results showed that the ATO-coated TEMs effectively block thermal radiation from sunlight. The temperature difference between ATO/TEMs treated cotton and the uncoated cotton fabric was 9 °C, and the thermal conductivity coatings were 0.0432 W/m⋅K. The UPF value of ATO/TEMs (ILs) coated cotton fabric is 440, significantly higher than pure cotton. This approach can provide insight into the design of high-performance solar insulation composite structures.

Development and Validation of a Knowledge Scale About the Behavioral and Psychological Symptoms of Dementia (KS-BPSD) Among Chinese Formal Caregivers.

OBJECTIVES: The current study aimed to develop a scale assessing knowledge about behavioral and psychological symptoms of dementia (KS-BPSD) among Chinese formal caregivers and to investigate its psychometric properties and factorial structure. METHODS: The scale was generated with a systematic development process, and 229 formal caregivers working at nursing homes were recruited to construct and assess the psychometric properties of the scale. The preliminary scale was reviewed by an expert panel and items were selected based on item discrimination, difficulty, and item-total correlation. RESULTS: The final KS-BPSD version consisted of 12 items, loaded into three factors (i.e., Disease Characteristics, Care and Risks, and Treatment Needs) following principal component analysis (PCA). The KS-BPSD showed good test-retest reliability, internal consistency, as well as construct and concurrent validity. CONCLUSIONS: The 12-item KS-BPSD was found to have high reliability and preliminary validity in assessing the level of knowledge about patient's BPSD among formal Chinese caregivers in nursing homes. CLINICAL IMPLICATIONS: KS-BPSD is a reliable tool to address the knowledge discrepancies and support needs among dementia caregivers, helping to develop and evaluate educational programs in the management of patient's BPSD.

Nanoparticle-mediated therapeutic management in cholangiocarcinoma drug targeting: Current progress and future prospects.

Patients with cholangiocarcinoma (CCA) often have an unfavorable prognosis because of its insidious nature, low resectability rate, and poor response to anticancer drugs and radiotherapy, which makes early detection and treatment difficult. At present, CCA has a five-year overall survival rate (OS) of only 5%, despite advances in therapies. New an increasing number of evidence suggests that nanoplatforms may play a crucial role in enhancing the pharmacological effects and in reducing both short- and long-term side effects of cancer treatment. This document reviews the advantages and shortcomings of nanoparticles such as liposomes, polymeric nanoparticle，inorganic nanoparticle, nano-metals and nano-alloys, carbon dots, nano-micelles, dendrimer, nano-capsule, bio-Nanomaterials in the diagnosis and treatment of CCA and discuss the current challenges in of nanoplatforms for CCA.

Effect of Chiglitazar and Sitagliptin on Bone Mineral Density and Body Composition in Untreated Patients with Type 2 Diabetes.

Aim: To evaluate the changes in bone mineral density (BMD) and body composition in untreated patients with type 2 diabetes mellitus (T2DM) before and after chiglitazar or sitagliptin treatment. Methods: A total of 81 patients with T2DM were randomly divided to receive chiglitazar or sitagliptin treatment for 24 weeks (54 in the chiglitazar group and 27 in the sitagliptin group). We measured the spine lumbar BMD, hip BMD, fat mass (FM), fat-free mass (FFM), percent body fat (%BF), android FM, gynoid FM and skeleton muscle mass (SMM) using dual-energy X-ray absorptiometry (DEXA) and examined serum adiponectin (ADP) levels at baseline and the end of the study. Results: There were no significant changes in the BMD of the L2-4, femoral neck, trochanter or total hip as well as in the BMC after 24 weeks of treatment with chiglitazar or sitagliptin. After chiglitazar administration, the FM, gynoid FM and gynoid to total FM ratio were higher, while the android to total FM ratio and the android to gynoid FM ratio (AOI) were significantly lower. Sitagliptin intervention did not result in statistically significant differences in total fat loss, but it did cause significant decreases in %BF and AOI as well as increases in the FFM, gynoid to total FM ratio and SMM. The ADP levels had significantly negative associations with AOI in all eligible patients. Conclusion: The chiglitazar had no deleterious effects on BMD and resulted in body fat redistribution in untreated patients with T2DM. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02173457).

Rituximab with high-dose methotrexate is effective and cost-effective in newly diagnosed primary central nervous system lymphoma.

Induction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3-4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Complete remission at the end of induction chemotherapy and ECOG > 3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and cost-effective combination treatment for PCNSLs, which warrants further evaluation in randomized trials.