Surgical treatment of multiple magnet ingestion by children: A single-center experience from China.

BACKGROUND: The incidence of magnet ingestion in children has escalated concurrent with the rise in popularity of magnetic playthings, bearing the capacity to induce substantial morbidity. AIM: The objective of this study was to encapsulate our accumulated expertise in handling pediatric cases featuring multiple magnetic foreign bodies within the gastrointestinal tract sometimes necessitating surgical intervention, as well as to formulate a clinical management algorithm. METHODS: This was a retrospective review of patients with multiple magnetic foreign bodies in the digestive tract, admitted to Shenzhen Children's Hospital, between January 2018 and December 2022. RESULTS: A total of 100 cases were included in this study, including 66 males and 34 females. The main clinical manifestation ns were abdominal pain and vomiting. All patients had abdominal x-ray, all of which indicated foreign bodies in the digestive tract. 33 patients had to undergo a surgical intervention. Among these cases, the gastrointestinal complications occurred in 31 patients, including gastric rupture (n = 9), intestinal obstruction (n = 11) and intestinal perforation (n = 30). Postoperative intestinal obstruction occurred in 6 children. There was no statistical significant difference in age and gender between the Surgical group and Non-surgical group, but the Surgical group had a higher number of magnets ([7.5(2-44) vs 4(2-20)], p = 0.009), a longer interval between time of misingestion to clinical visit ([48(7.2-480) vs 5(2-336)]hours, p < 0.001), and a longer length of hospital stay ([10(6-19) vs 2(1-8)]days, p < 0.001). CONCLUSIONS: Multiple magnet ingestion in children can lead to serious complications and carry severe risks. Timely diagnosis and effective treatment are crucial for managing such patients.

Thermal Proteome Profiling Strategy Identifies CNPY3 as a Cellular Target of Gambogic Acid for Inducing Prostate Cancer Pyroptosis.

There is an urgent requirement to acquire a comprehensive comprehension of novel therapeutic targets for prostate cancer to facilitate the development of medications with innovative mechanisms. In this study, we identified gambogic acid (GBA) as a specific pyroptosis inducer in prostatic cancer cells. By using a thermal proteome profiling (TPP) strategy, we revealed that GBA induces pyroptosis by directly targeting the canopy FGF signaling regulator (CNPY3), which was previously considered "undruggable". Moreover, through the utilization of the APEX2-based proximity labeling method, we found that GBA recruited delactatease SIRT1, resulting in the elimination of lysine lactylation (Kla) on CNPY3. Of note, SIRT1-mediated delactylation influenced the cellular localization of CNPY3 to promote lysosome rupture for triggering pyroptosis. Taken together, our study identified CNPY3 as a distinctive cellular target for pyroptosis induction and its potential application in prostate cancer therapy.

The causal effect of hypertension, intraocular pressure, and diabetic retinopathy: a Mendelian randomization study.

Background: Previous research has indicated a vital association between hypertension, intraocular pressure (IOP), and diabetic retinopathy (DR); however, the relationship has not been elucidated. In this study, we aim to investigate the causal association of hypertension, IOP, and DR. Methods: The genome-wide association study (GWAS) IDs for DR, hypertension, and IOP were identified from the Integrative Epidemiology Unit (IEU) Open GWAS database. There were 33,519,037 single-nucleotide polymorphisms (SNPs) and a sample size of 1,030,836 for DR. There were 16,380,466 SNPs and 218,754 participants in the hypertension experiment. There were 9,851,867 SNPs and a sample size of 97,465 for IOP. Univariable, multivariable, and bidirectional Mendelian randomization (MR) studies were conducted to estimate the risk of hypertension and IOP in DR. Moreover, causality was examined using the inverse variance weighted method, and MR results were verified by numerous sensitivity analyses. Results: A total of 62 SNPs at the genome-wide significance level were selected as instrumental variables (IVs) for hypertension-DR. The results of univariable MR analysis suggested a causal relationship between hypertension and DR and regarded hypertension as a risk factor for DR [p = 0.006, odds ratio (OR) = 1.080]. A total of 95 SNPs at the genome-wide significance level were selected as IVs for IOP-DR. Similarly, IOP was causally associated with DR and was a risk factor for DR (p = 0.029, OR = 1.090). The results of reverse MR analysis showed that DR was a risk factor for hypertension (p = 1.27×10-10, OR = 1.119), but there was no causal relationship between DR and IOP (p > 0.05). The results of multivariate MR analysis revealed that hypertension and IOP were risk factors for DR, which exhibited higher risk scores (p = 0.001, OR = 1.121 and p = 0.030, OR = 1.124, respectively) than those in univariable MR analysis. Therefore, hypertension remained a risk factor for DR after excluding the interference of IOP, and IOP was still a risk factor for DR after excluding the interference of hypertension. Conclusion: This study validated the potential causal relationship between hypertension, IOP, and DR using MR analysis, providing a reference for the targeted prevention of DR.

Utilizing symmetrical tetramethyl cucurbit[6]uril-based supramolecular fluorescence probe for detection of paraquat in water.

A supramolecular fluorescence probe has been developed using a symmetrical tetramethyl cucurbit[6]uril (TMeQ[6]) and a styryl derivative (SPy) with a host-guest ratio of 2:1. The introduction of paraquat (PQ) competes with SPy for the TMeQ[6] cavity, resulting in fluorescent quenching. The addition of 17 common herbicides and ions had negligible effects on the fluorescence quenching, indicating that the 2TMeQ[6]/SPy complex exhibits excellent selectivity in detecting PQ. The detection limit was found to be 4.62 × 10-7 M. More importantly, the probe was engineered to detect paraquat in river water by examining post-treatment samples and noting alterations in fluorescence color. The red to blue (R/B) intensity ratio is subsequently calculated to ascertain the PQ concentration. Experimental trials conducted on river water samples yielded recovery rates between 98.21 % and 108 %, with a relative standard deviation of less than 5 %. By pairing this with a smartphone-based colorimetric analysis application, we can facilitate portable PQ detection, enabling efficient and convenient monitoring across various locations.

Targeting autophagy in Alzheimer's disease: Animal models and mechanisms.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that leads to cognitive impairment and memory loss. Emerging evidence suggests that autophagy plays an important role in the pathogenesis of AD through the regulation of amyloid-beta (Aß) and tau metabolism, and that autophagy dysfunction exacerbates amyloidosis and tau pathology. Therefore, targeting autophagy may be an effective approach for the treatment of AD. Animal models are considered useful tools for investigating the pathogenic mechanisms and therapeutic strategies of diseases. This review aims to summarize the pathological alterations in autophagy in representative AD animal models and to present recent studies on newly discovered autophagy-stimulating interventions in animal AD models. Finally, the opportunities, difficulties, and future directions of autophagy targeting in AD therapy are discussed.

GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21.

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing.

Rotational isomerization: spontaneous structural transformation of a thermally activated delayed fluorescence binuclear copper(I) complex.

A novel binuclear Cu(I) halide complex, Cu2I2(DPPCz)2, which emits efficient thermally activated delayed fluorescence (TADF), is reported. The crystal of this complex spontaneously undergoes ligand rotation and coordination-configuration transformation, converting to its isomer without any external stimulation.

Sensitivity to thyroid hormone indices are associated with papillary thyroid carcinoma in Chinese patients with thyroid nodules.

BACKGROUND: The association between thyroid hormone sensitivity and thyroid cancer is unknown, and we aimed to investigate the association between sensitivity to thyroid hormone indices and papillary thyroid carcinoma (PTC) in Chinese patients with thyroid nodules (TNs). METHODS: A total of 1,998 patients undergoing thyroid surgery due to TNs from Nanjing Drum Tower Hospital were included in this study. We evaluated central sensitivity to thyroid hormones, such as thyroid stimulating hormone index (TSHI), TSH T4 resistance index (TT4RI), thyroid feedback quantile-based index (TFQI), and parametric thyroid feedback quantile-based Index (PTFQI). Peripheral sensitivity to thyroid hormone was evaluated by FT3 to FT4 ratio. Multivariate logistic regression analysis was performed to evaluate the association between sensitivity to thyroid hormone indices and PTC risk. RESULTS: The results showed that central indices of thyroid hormone sensitivity, including TSHI, TT4RI, TFQI, and PTFQI, were positively associated with PTC risk. For each SD increase in TSHI, TT4RI, TFQI, and PTFQI, the odds ratios (OR, 95% CI) of PTC were 1.31 (1.18-1.46), 1.01 (1.01-1.02), 1.94 (1.45-2.60), and 1.82 (1.41-2.34), respectively. On the other hand, the association between peripheral sensitivity to thyroid hormone and PTC was significantly negative. For each SD increase in FT3/FT4 ratio, the OR (95% CI) of PTC was 0.18 (0.03-0.96), and a negative correlation was found between FT3/FT4 ratio and TNM staging of PTC. CONCLUSIONS: Sensitivity to thyroid hormone indices could be used as new indicators for predicting PTC in Chinese patients with TNs. Future researches are still needed to confirm our findings.

High-Contrast Visualization Chemiluminescence Based on AIE-Active and Base-Sensitive Emitters.

Peroxyoxalate chemiluminescence (PO-CL) is one of the most popular cold light sources, yet the drawback of aggregation-caused quenching limits their use. Here, we report a new kind of efficient bifunctional emitter derived from salicylic acid, which not only exhibits typical aggregation-induced emission (AIE) character but also has the ability to catalyze the CL process under basic conditions based on base sensitivity. By taking advantage of these unique features, we successfully confine the CL process on the surface of solid bases and provide a high-contrast visualization of CL emission. This method allows most of the common basic salts like sodium carbonate to be invisible encryption information ink and PO-CL solution to be a decryption tool to visualize the hidden information. The current study opens up an appealing way for the development of multifunction CL emitters for information encryption and decryption applications.

Allosteric Activation of Transglutaminase 2 via Inducing an "Open" Conformation for Osteoblast Differentiation.

Osteoblasts play an important role in the regulation of bone homeostasis throughout life. Thus, the damage of osteoblasts can lead to serious skeletal diseases, highlighting the urgent need for novel pharmacological targets. This study introduces chemical genetics strategy by using small molecule forskolin (FSK) as a probe to explore the druggable targets for osteoporosis. Here, this work reveals that transglutaminase 2 (TGM2) served as a major cellular target of FSK to obviously induce osteoblast differentiation. Then, this work identifies a previously undisclosed allosteric site in the catalytic core of TGM2. In particular, FSK formed multiple hydrogen bonds in a saddle-like domain to induce an "open" conformation of the ß-sandwich domain in TGM2, thereby promoting the substrate protein crosslinks by incorporating polyamine. Furthermore, this work finds that TGM2 interacted with several mitochondrial homeostasis-associated proteins to improve mitochondrial dynamics and ATP production for osteoblast differentiation. Finally, this work observes that FSK effectively ameliorated osteoporosis in the ovariectomy mice model. Taken together, these findings show a previously undescribed pharmacological allosteric site on TGM2 for osteoporosis treatment, and also provide an available chemical tool for interrogating TGM2 biology and developing bone anabolic agent.

Evidence synthesis of Chinese medicine for monkeypox: Suggestions from other contagious pox-like viral diseases.

Background: Monkeypox, a zoonotic disease caused by an Orthopoxvirus, presents an etiology similar to smallpox in humans. Currently, there are no licensed treatments for human monkeypox, so clear and urgent research on its prophylaxis and treatment is needed. Objective: The purpose of this study was to explore the evidence of Chinese medicine for contagious pox-like viral diseases and provide suggestions for the multi-country outbreak management of monkeypox. Methods: The review was registered on INPLASY (INPLASY202270013). Ancient classics in China and clinical trials involving randomized controlled trials , non-RCTs, and comparative observational studies of CM on the prevention and treatment of monkeypox, smallpox, measles, varicella, and rubella were retrieved from the Chinese Medical Code (fifth edition), Database of China Ancient Medicine, PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP, Wanfang, Google Scholar, International Clinical Trial Registry Platform, and Chinese Clinical Trial Registry until 6 July 2022. Both quantitative and qualitative methods were applied to present the data collected. Results: The use of CM to control contagious pox-like viral diseases was traced back to ancient Chinese practice cited in Huangdi's Internal Classic, where the pathogen was recorded nearly two thousand years back. There were 85 articles (36 RCTs, eight non-RCTs, one cohort study, and 40 case series) that met the inclusion criteria, of which 39 studies were for measles, 38 for varicella, and eight for rubella. Compared with Western medicine for contagious pox-like viral diseases, CM combined with Western medicine showed significant improvements in fever clearance time (mean difference, -1.42 days; 95% CI, -1.89 to -0.95; 10 RCTs), rash/pox extinction time (MD, -1.71 days; 95% CI, -2.65 to -0.76; six RCTs), and rash/pox scab time (MD, -1.57 days; 95% CI, -1.94 to -1.19; five RCTs). When compared with Western medicine, CM alone could reduce the time of rash/pox extinction and fever clearance. Chinese herbal formulas, including modified Yinqiao powder, modified Xijiao Dihaung decoction, modified Qingjie Toubiao decoction, and modified Shengma Gegen decoction, were frequently applied to treat pox-like viral diseases and also showed significant effects in shortening the time of fever clearance, rash/pox extinction, and rash/pox scabs. Compared with Western medicine (placental globulin) or no intervention, eight non-randomized trials and observational studies on the prevention of contagious pox-like viral diseases showed a significant preventive effect of Leiji powder among high-risk populations. Conclusion: Based on historical records and clinical studies of CM in managing contagious pox-like viral diseases, some botanical drugs could be an alternative approach for treating and preventing human monkeypox. Prospective, rigorous clinical trials are urgently needed to confirm the potential preventive and treatment effect of Chinese herbal formulas. Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY202270013].

Epidermal growth factor receptor inhibitors as adjuvant treatment for patients with resected non-small cell lung cancer harboring EGFR mutation: a meta-analysis of randomized controlled clinical trials.

BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is still under investigation as adjuvant treatment for early-stage disease. Here, we performed a meta-analysis to evaluate the efficacy of adjuvant EGFR-TKI versus non-EGFR-TKI treatment in patients with completely resected non-small cell lung cancer (NSCLC) harboring EGFR mutation. METHODS: Two investigators independently extracted data from databases. A meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered in PROSPERO (ID: CRD42022316481). The primary outcome was disease-free survival (DFS) in patients with EGFR mutation, measured as the hazard ratio (HR). Other outcomes (of subgroup analyses) included overall survival (OS) and DFS. RESULTS: After the systematic screening, eight studies with a total of 3098 patients with stage IB-IIIA NSCLC were included. The results show that in patients with EGFR mutation, the DFS in the adjuvant EGFR-TKI group was significantly superior to that in the control group, with a HR of 0.47 (95% confidence interval [CI]: 0.30-0.74; P = 0.001). In subgroup analyses of DFS, the benefit was observed in the EGFR-TKI group versus the chemotherapy group (HR 0.50, 95% CI 0.30-0.84; P = 0.009), the EGFR-TKI combined with chemotherapy group versus the chemotherapy group (HR 0.37, 95% CI 0.16-0.85; P = 0.02), and in stage IIA-IIIA NSCLC (HR 0.45, 95% CI 0.27-0.74; P = 0.002). However, the benefit of DFS did not translate into improved OS in the whole population (HR 0.79, 95% CI 0.54-1.14; P = 0.20). CONCLUSION: EGFR-TKIs prolonged DFS but not OS in patients with completely resected stage II-IIIA NSCLC harboring EGFR mutation. Longer follow-ups and new clinical trials that can result in changes in clinical practice are needed.

Chinese herbal medicine for drug-induced liver injury in patients with HIV/AIDS: A systematic review of randomized controlled trials.

Background: To explore the effectiveness and safety of Chinese herbal medicine (CHM) for drug-induced liver injury (DILI) in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Methods: A systematic search was made of eight databases (Pubmed, Cochrane Library, Web of Science, Embase, CNKI, Wanfang, VIP, Sinomed) and two trial registries (WHO ICTRP, ClinicalTrials.gov) from inception to September 2022. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI). The Cochrane Risk of Bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tools were used for quality appraisal. Results: Ten randomized controlled trials (RCTs) involving 732 participants were included. Comparing CHM alone with routine treatment, the CHM group showed lower aspartate aminotransferase (MD=-11.47 U/L, 95%CI[-13.05, -9.89], low certainty), lower alanine aminotransferase (MD=-2.68 U/L, 95%CI[-4.27, -1.08], low certainty), lower total bilirubin (MD=-4.31 mmol/L, 95%CI[-5.66, -2.96], low certainty), lower bilirubin direct (MD=-3.19 mmol/L, 95%CI[-3.87, -2.51], low certainty), and higher effective rate (assessed by symptoms and liver indicators) (RR=1.13, 95%CI[1.06, 1.20], low certainty). A significant difference was also found in CHM plus routine treatment versus routine treatment in the previous outcomes. No significant difference was found on helper T cells among these comparisons. Only one RCT reported safety of CHM and found no adverse reaction during the trial. Conclusions: CHM may improve the liver function indices and effective rate for HIV/AIDS patients with DILI. However, the sample size was small and quality was low. Larger-samples of high-quality trials are needed.

Application of the combination method based on RF and LE in near infrared spectral modeling.

The dimensionality of near-infrared (NIR) spectral data is often extremely large. Dimensionality reduction of spectral data can effectively reduce the redundant information and correlation between spectral variables and simplify the model, which is crucial to increasing the model's performance. As a nonlinear feature extraction method, Laplacian Eigenmaps (LE) may preserve the local neighborhood information of the dataset, has high robustness, and is simple to compute. However, when the LE algorithm maps the data from high-dimensional space to low-dimensional space, it is often disturbed by irrelevant information and multicollinearity in the spectral data, which lowers the model's prediction performance. Random Frog (RF) algorithm can eliminate noise and collinearity in the spectrum. Therefore, before using the LE algorithm, we use the RF algorithm to eliminate irrelevant information in the spectrum and reduce the correlation between the spectra variables to increase the efficiency of the LE algorithm. We used the RF + LE algorithm to reduce the dimensionality of two public NIRS datasets (soil datasets and pharmaceutical tablets datasets) and compared it with RF and LE algorithms alone. We utilized Partial Least Squares Regression (PLSR) and Support Vector Regression (SVR) to establish regression models. The experimental findings demonstrate that compared with the RF algorithm and LE algorithm, the RF + LE combination method can reduce the dimension of spectral variables and model complexity, and improve regression models' prediction accuracy and stability. It is an effective dimensionality reduction method for the near-infrared spectrum.

Inherent Capability of Self-Assembling Nanostructures in Specific Proteasome Activation for Cancer Cell Pyroptosis.

Understanding the direct interaction of nanostructures per se with biological systems is important for biomedical applications. However, whether nanostructures regulate biological systems by targeting specific cellular proteins remains largely unknown. In the present work, self-assembling nanomicelles are constructed using small-molecule oleanolic acid (OA) as a molecular template. Unexpectedly, without modifications by functional ligands, OA nanomicelles significantly activate cellular proteasome function by directly binding to 20S proteasome subunit alpha 6 (PSMA6). Mechanism study reveals that OA nanomicelles interact with PSMA6 to dynamically modulate its N-terminal domain conformation change, thereby controlling the entry of proteins into 20S proteasome. Subsequently, OA nanomicelles accelerate the degradation of several crucial proteins, thus potently driving cancer cell pyroptosis. For translational medicine, OA nanomicelles exhibit a significant anticancer potential in tumor-bearing mouse models and stimulate immune cell infiltration. Collectively, this proof-of-concept study advances the mechanical understanding of nanostructure-guided biological effects via their inherent capacity to activate proteasome.

Knockdown of FGFR3 inhibits the proliferation, migration and invasion of intrahepatic cholangiocarcinoma.

The FGF/FGFR signaling axis deregulation of the fibroblast growth factor receptor (FGFR) family is closely related to tumorigenesis, tumor progression and drug resistance to anticancer therapy. And fibroblast growth factor receptor 3 (FGFR3) is one member of this family. In this study, we aimed to investigate the effect of siRNA-induced knockdown of FGFR3 on the biological behaviors of intrahepatic cholangiocarcinoma (ICC). The expression levels of FGFR3 were determined in three intrahepatic cholangiocarcinoma cell lines RBE, HUCCT1 and HCCC9810 cell lines by Western blot. FGFR3 expression in RBE cell line was knocked down by siRNA. Our study found that knockdown of FGFR3 inhibited the migration, invasion and proliferation of ICC cells using Wound healing assay, Transwell migration and invasion assays and Cell proliferation assay. And significantly down-regulated the protein expression levels of MMP2, cyclinD1, and NCadherin, but had no significant effect on MMP9, cyclinD3, vimentin, E-cadherin protein. In addition, we found that ERK/c-Myc presumably is its signaling pathway by bioinformatics analysis and Western blot verification. To sum up, knockdown of FGFR3 inhibited the migration, invasion and proliferation of ICC cells. It demonstrated that FGFR3 probably becomes a therapeutic target for ICC and increases the proportion of potentially curable intrahepatic cholangiocarcinoma patients treated with FGFR inhibitors.

NSUN5 promotes progression and predicts poor prognosis in hepatocellular carcinoma.

The 5-methylcytosine (m5C) RNA methyltransferase NOP2/Sun RNA methyltransferase 5 (NSUN5) has been reported to serve important roles in numerous diseases. However, the functions and clinical significance of NSUN5 in hepatocellular carcinoma (HCC) remain unknown. Clinical information and NSUN5 mRNA sequencing data for 374 patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and NSUN5 mRNA and protein expression levels in 120 patients with HCC (present study cohorts) were assessed using reverse transcription-quantitative PCR, western blotting or immunohistochemistry. The association between NSUN5 mRNA and protein expression levels and the clinical characteristics (or prognosis) of patients with HCC was analyzed using the χ2 or log-rank test. The functions of NSUN5 in HCC were evaluated using in vitro and in vivo experiments, and the mechanism by which NSUN5 affected the progression of HCC was assessed using bioinformatics analysis using LinkedOmics. NSUN5 was significantly upregulated and predicted poor prognosis in HCC according to data from both TCGA database and present study cohorts. NSUN5 significantly promoted HCC proliferation and migration in vitro and significantly induced HCC tumor growth in vivo. Bioinformatics analysis demonstrated that NSUN5 was positively correlated with genes associated with translation in HCC. It was hypothesized that overexpression of NSUN5 strengthened ribosome functions and global protein translation, which may promote the proliferation and migration of HCC. In conclusion, NSUN5 may promote the progression of HCC by enhancing translation, thus making it a potential target for HCC treatment.

Acupuncture for cancer-related conditions: An overview of systematic reviews.

BACKGROUND: Acupuncture is commonly used for cancer-related conditions worldwide, and evidence is increasing year on year. There is a need to summarize the evidence of acupuncture for cancer-related conditions comprehensively and critically. OBJECTIVE: To evaluate and summarize the systematic reviews (SRs) that assess the effects and safety of acupuncture for cancer-related conditions, and to inform clinical practice and future studies. METHODS: A comprehensive search was conducted on Pubmed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Sinomed, and Wanfang from their inception to October 16, 2021. SRs of randomized controlled trials (RCTs) on acupuncture for cancer-related conditions were to be included. Two reviewers screened the eligible articles, and four reviewers in pair extracted data and assessed the methodological quality/risk of bias of all included reviews by AMSTAR 2 and ROBIS tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a summary of meta-analysis or narrative description. RESULTS: Fifty-one SRs of RCTs on acupuncture for cancer-related conditions were included and synthesized. The methodological quality of SRs included 1 "high", 5 "low" and 45 "very low" by AMSTAR 2. Sixteen SRs assessed as low risk of bias (31.37%), and 35 SRs had high risk of bias (68.63%) by ROBIS. Acupuncture showed effective on systemic conditions in relation to different cancers, including cancer-related pain (17 SRs, 80 RCTs), fatigue (7 SRs, 18 RCTs), insomnia (4 SRs, 10 RCTs), quality of life (2 SRs, 15 RCTs); conditions in relation to chemo-radiotherapy, including nausea and vomiting (3 SRs, 36 RCTs) and bone marrow suppression (2 SRs, 21 RCTs); and conditions in relation to specific cancers, including breast cancer-related menopause (3 SRs, 6 RCTs), hot flashes (12 SRs, 13 RCTs), arthralgia (5 SRs, 10 RCTs), and nasopharyngeal cancer-related dysphagia (1 SRs, 7 RCTs). Acupuncture appeared to have benefit for patients with lymphoedema (3 SRs, 3 RCTs), gastrointestinal function (5 SRs, 27 RCTs), and xerostomia (4 SRs, 7 RCTs). Limited evidence showed inconsistent results on acupuncture for chemotherapy-induced peripheral neuropathy (3 SRs, 6 RCTs), depression and anxiety (3 SRs, 9 RCTs). Acupuncture was regarded as a safe therapy for cancer patients as no severe adverse events related were reported. CONCLUSION: Evidence from SRs showed that acupuncture is beneficial to cancer survivors with cancer-related pain, fatigue, insomnia, improved quality of life, nausea and vomiting, bone marrow suppression, menopausal symptoms, arthralgia, and dysphagia, and may also be potential for lymphoedema, gastrointestinal function, and xerostomia. For neuropathy, depression and anxiety, acupuncture should be used as an option based on individual conditions. Acupuncture is relatively safe without serious adverse events. More well-designed clinical trials of acupuncture are recommended on cancer-related depression and anxiety, arthralgia, xerostomia, gastrointestinal dysfunction and dysphagia.

Neuroinflammation inhibition by small-molecule targeting USP7 noncatalytic domain for neurodegenerative disease therapy.

Neuroinflammation is a fundamental contributor to progressive neuronal damage, which arouses a heightened interest in neurodegenerative disease therapy. Ubiquitin-specific protease 7 (USP7) has a crucial role in regulating protein stability in multiple biological processes; however, the potential role of USP7 in neurodegenerative progression is poorly understood. Here, we discover the natural small molecule eupalinolide B (EB), which targets USP7 to inhibit microglia activation. Cocrystal structure reveals a previously undisclosed covalent allosteric site, Cys576, in a unique noncatalytic HUBL domain. By selectively modifying Cys576, EB allosterically inhibits USP7 to cause a ubiquitination-dependent degradation of Keap1. Keap1 function loss further results in an Nrf2-dependent transcription activation of anti-neuroinflammation genes in microglia. In vivo, pharmacological USP7 inhibition attenuates microglia activation and resultant neuron injury, thereby notably improving behavioral deficits in dementia and Parkinson's disease mouse models. Collectively, our findings provide an attractive future direction for neurodegenerative disease therapy by inhibiting microglia-mediated neuroinflammation by targeting USP7.

Application of adaptive Laplacian Eigenmaps in near infrared spectral modeling.

Laplacian Eigenmaps is a nonlinear dimensionality reduction algorithm based on graph theory. The algorithm adopted the Gaussian function to measure the affinity between a pair of points in the adjacency graph. However, the scaling parameter σ in the Gaussian function is a hyper-parameter tuned empirically. Once the value of σ is determined and fixed, the weight between two points depends wholly on the Euclidian distance between them, which is not suitable for multi-scale sample sets. To optimize the weight between two points in the adjacency graph and make the weight reflect the scale information of different sample sets, an adaptive LE improved algorithm is used in this paper. Considering the influence of adjacent sample points and multi-scale data, the Euclidean distance between the k-th nearest sample point to sample point xi is used as the local scaling parameter σi of xi, instead of using a single scaling parameter σ. The efficiency of the algorithm is testified by applying on two public near-infrared data sets. LE-SVR and ALE-SVR models are established after LE and ALE dimension reduction of SNV preprocessed data sets. Compared with the LE-SVR model, the R2 and RPD of the ALE-SVR model established on the two data sets are improved, while RMSE is decreased, indicating that the prediction effect and stability of the regression model are established by the ALE algorithm are better than that of the traditional LE algorithm. Experiments show that the ALE algorithm can achieve a better dimensionality reduction effect than the LE algorithm.