The self-correction and influence factors of congenital auricular deformity: A prospective cohort study.

OBJECTIVE: To prospectively observe the self-correction of congenital auricular deformity (CAD) and explore the potential factors affecting the self-correction. METHODS: This study was a multi-center prospective observational study. Newborns aged 0-3 days from 12 Maternal and Child Health Hospitals or Maternity Hospitals were chosen as the participants and prospectively followed up until week 6 after birth. The primary and secondary outcome was the score of deformity, and the secondary outcome was the improvement rate, respectively. RESULTS: A total of 135 newborns diagnosed with CAD (237 ears) were recruited. Boys and girls accounted for 50.37% (117 ears) and 49.63% (120 ears). The top morphological type was the constricted ear (107 ears, 45.15%). The score of deformity at baseline, week 3, and week 6 after enrollment was 4.00, 3.00, and 2.00, decreasing over time (P < 0.05). The higher the severity of deformity, the worse the self-correcting effect (P < 0.05). The scores of deformity of Stahl's ear were lower than those of others after follow-up (P < 0.05). No significant differences among the scores of deformity in different genders (P >0.05). The total improvement rate at week 3 and week 6 was 29.96% (71/237 ears) and 37.13% (88/237), respectively. The improvement rate of the Stahl's ear at week 3 and week 6 after enrollment was higher than that of four other morphological types (P < 0.05). CONCLUSIONS: Some CAD tends to self-correction, but for most CADs, there is still a need for early correction. Morphological types and severity of deformity are the main influencing factors on self-correcting effect, whereas sex was not.

Assessment of antibiotic consumption patterns in hospital and primary healthcare using WHO Access, Watch and Reserve classification (AWaRe) in Sichuan Western China: 2020.

BACKGROUND: The Access, Watch, and Reserve (AWaRe) classification of antibiotics was a useful tool to support antibiotic stewardship. However, the AWaRe patterns of antibiotic consumption in Western China were unclear. We aimed to assess the antibiotic consumption patterns using the AWaRe Classification of public hospitals in Sichuan Province Western China. METHODS: Antibiotic consumption data of year 2020 were obtained from the Sichuan Province Drug Use Monitoring Platform. We measured the antibiotic consumption (DDDs per 1,000 inhabitants per day, DIDs), calculated the proportion of antibiotic use, the ratio of Access to Watch antibiotics and patterns of antibiotic use by using drug utilization 90%. RESULTS: This analysis included 4452 public health institutions. The antibiotic consumption rate was 10.39 DIDs (Median 8.50, IQR 7.71-12.96). The proportions of Access antibiotic use and Watch antibiotic use were 46.83% (Median 47.49, IQR 44.16-52.02) and 51.20% (Median 51.43, IQR 45.42-54.61), respectively. The Access-to-Watch index was 0.91 (Median 0.92, IQR 0.81-1.15). Amoxicillin (16.85%), cefuroxime (9.21%), cefixime (8.60%%), levofloxacin (8.11%) and metronidazole (6.16%) were the most consumed antibiotics. CONCLUSIONS: The proportion of Access antibiotic consumption in Sichuan Western China has not achieved the WHO target of 60%. Overuse of antibiotic is serious in Sichuan. National and regional antibiotics management systems, stewardship programs and surveillance of antibiotic consumption based on AWaRe classification are needed to improve antibiotic consumption patterns, curb antibiotic overuse and combat antimicrobial resistance in Western China.

Nanozymes as Glucose Scavengers and Oxygenerators for Enhancing Tumor Radiotherapy.

Insufficient accumulation of reactive oxygen species (ROS) due to tumor hypoxia significantly contributes to increased radiation resistance and the failure of radiotherapy (RT). Therefore, developing methods to alleviate hypoxia and boost ROS levels represents a promising strategy for enhanced radiosensitivity. This study introduced a self-cascade catalytic Pt@Au nanozymes as a radiosensitizer, using glucose oxidase (GOx)-, catalase (CAT)-, and peroxidase (POD)-like activities to improve hypoxia and increase ROS accumulation, thereby affecting glucose metabolism and enhancing the effects of RT. Pt@Au nanozymes exhibit GOx-like activity, which not only depletes glucose to induce starvation therapy, but also generates hydrogen peroxide (H2O2) for cascade reactions. Moreover, Pt@Au nanozymes demonstrate CAT-like activity, catalyzing the conversion of H2O2 to O2. This conversion effectively alleviates hypoxia, stabilizes ROS, increases DNA damage, significantly enhancing RT efficacy and sustaining the effects of starvation therapy. As high-Z materials, Pt@Au nanozymes can deposit more X-ray energy. Furthermore, the POD-like activity catalyzes the conversion of H2O2 into highly reactive hydroxyl radicals (·OH), which increases ROS levels and enhances RT. Pt@Au nanozymes serve as X-ray computed tomography (CT) imaging agents, allowing for clear differentiation between tumor and normal tissue boundaries and enhancing the precision of RT. In summary, Pt@Au nanozymes serve as effective radiosensitizers by depleting glucose to induce starvation therapy, enhancing cascade reactions, and inhibiting tumor proliferation. Through their self-cascade reactions, these nanozymes dramatically increase oxygen levels within tumors, reduce hypoxia, and enhance ROS levels. This advancement addresses the radioresistance associated with hypoxic tumors, paving the way for innovative strategies in RT.

Patient-reported outcome measures for medication treatment satisfaction: a systematic review of measure development and measurement properties.

BACKGROUND: Medication Treatment Satisfaction (M-TS) from the patients' perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps. METHODS: Using PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM ). RESULTS: This review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test-retest reliability, results in 24 provided evidence of satisfactory test-retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability. CONCLUSIONS: Most existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS.

Visual Feature-Guided Diamond Convolutional Network for Finger Vein Recognition.

Finger vein (FV) biometrics have garnered considerable attention due to their inherent non-contact nature and high security, exhibiting tremendous potential in identity authentication and beyond. Nevertheless, challenges pertaining to the scarcity of training data and inconsistent image quality continue to impede the effectiveness of finger vein recognition (FVR) systems. To tackle these challenges, we introduce the visual feature-guided diamond convolutional network (dubbed 'VF-DCN'), a uniquely configured multi-scale and multi-orientation convolutional neural network. The VF-DCN showcases three pivotal innovations: Firstly, it meticulously tunes the convolutional kernels through multi-scale Log-Gabor filters. Secondly, it implements a distinctive diamond-shaped convolutional kernel architecture inspired by human visual perception. This design intelligently allocates more orientational filters to medium scales, which inherently carry richer information. In contrast, at extreme scales, the use of orientational filters is minimized to simulate the natural blurring of objects at extreme focal lengths. Thirdly, the network boasts a deliberate three-layer configuration and fully unsupervised training process, prioritizing simplicity and optimal performance. Extensive experiments are conducted on four FV databases, including MMCBNU_6000, FV_USM, HKPU, and ZSC_FV. The experimental results reveal that VF-DCN achieves remarkable improvement with equal error rates (EERs) of 0.17%, 0.19%, 2.11%, and 0.65%, respectively, and Accuracy Rates (ACC) of 100%, 99.97%, 98.92%, and 99.36%, respectively. These results indicate that, compared with some existing FVR approaches, the proposed VF-DCN not only achieves notable recognition accuracy but also shows fewer number of parameters and lower model complexity. Moreover, VF-DCN exhibits superior robustness across diverse FV databases.

Bidirectional associations between sleep and anxiety among Chinese schoolchildren before and after the COVID-19 lockdown.

The COVID-19 pandemic has critical implications for mental health in children. This study examined how the COVID-19 lockdown affected sleep duration and anxiety symptoms in Chinese school-aged children and the bidirectional association between sleep and anxiety before and during the COVID-19 lockdown. A school-based longitudinal cohort study was conducted to examine the relationship between sleep duration and anxiety scores before and after the COVID-19 lockdown from January to May 2020. Generalized estimating equations model was used to identify variables that contributed to the changes in sleep duration. The bidirectional relationship between sleep duration and anxiety symptoms was explored by cross-lagged analysis. 7681 children completed two waves of surveys were included in the analysis. The daily exercise duration, anxiety symptoms, and sleep duration decreased significantly during the lockdown compared with that before the lockdown. Based on generalized estimating equations model, older age, secondary school, and higher anxiety scores of participants were positively associated with sleep duration, while female and no COVID-19 infection history were negatively associated with it. Cross-lagged analysis showed higher anxiety score of children before the lockdown was significantly associated with shorter sleep duration during the lockdown; and shorter sleep duration of children before the lockdown was also significantly associated with a higher anxiety score during the lockdown. Under the context of the COVID-19 pandemic, there were longitudinal, bidirectional associations between children's anxiety symptoms and sleep duration. For school students, mental health services and sleep education should be considered in the daily health education curriculum.

Presenilin deficiency enhances tau phosphorylation and its secretion.

Alzheimer's disease (AD) is characterized by the accumulation of abnormally folded amyloid ß-protein (Aß) in the brain parenchyma and phosphorylated tau in neurons. Presenilin (PS, PSEN) 1 and PS2 are essential components of γ-secretase, which is responsible for the cleavage of amyloid precursor protein (APP) to generate Aß. PSEN mutations are associated with tau aggregation in frontotemporal dementia, regardless of the presence or absence of Aß pathology. However, the mechanism by which PS regulates tau aggregation is still unknown. Here, we found that tau phosphorylation and secretion were significantly increased in PS double-knock-out (PS1/2-/-) fibroblasts compared with wild-type fibroblasts. Tau-positive vesicles in the cytoplasm were significantly increased in PS1/2-/- fibroblasts. Active GSK-3ß was increased in PS1/2-/- fibroblasts, and inhibiting GSK3ß activity in PS1/2-/- fibroblasts resulted in decreased tau phosphorylation and secretion. Transfection of WT human PS1 and PS2 reduced the secretion of phosphorylated tau and active GSK-3ß in PS1/2-/- fibroblasts. However, PS1D257A without γ-secretase activity did not decrease the secretion of phosphorylated tau. Furthermore, nicastrin deficiency also increased tau phosphorylation and secretion. These results suggest that deficient PS complex maturation may increase tau phosphorylation and secretion. Thus, our studies discover a new pathway by which PS regulates tau phosphorylation/secretion and pathology independent of Aß and suggest that PS serves as a potential therapeutic target for treating neurodegenerative diseases involving tau aggregation.

A Chemoselective Enrichment Strategy for In-Depth Coverage of the Methyllysine Proteome.

Proteomics is a powerful method to comprehensively understand cellular posttranslational modifications (PTMs). Owing to low abundance, tryptic peptides with PTMs are usually enriched for enhanced coverage by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Affinity chromatography for phosphoproteomes by metal-oxide and pan-specific antibodies for lysine acetylome allow identification of tens of thousands of modification sites. Lysine methylation is a significant PTM; however, only hundreds of methylation sites were identified by available approaches. Herein we report an aryl diazonium based chemoselective strategy that enables enrichment of monomethyllysine (Kme1) peptides through covalent bonds with extraordinary sensitivity. We identified more than 10000 Kme1 peptides from diverse cell lines and mouse tissues, which implied a wide lysine methylation impact on cellular processes. Furthermore, we found a significant amount of methyl marks that were not S-adenosyl methionine (SAM)-dependent by isotope labeling experiments.

Sanxiapeptin is an ideal preservative with a dual effect of controlling green mold and inducing systemic defense in postharvest citrus.

Green mold is a common postharvest disease infected by Penicillium digitatum that causes citrus fruit decay, and severely affects fruit storage quality. This work aimed to investigate the antifungal activity of Sanxiapeptin against P. digitatum, and elucidate the possible mechanisms involved. Sanxiapeptin was capable of inhibiting spore germination, germ tube length and mycelial growth. The SYTOX green staining assay revealed that Sanxiapeptin targeted the fungal membrane, and changed the membrane permeability, leading to the leakage of cell constituents. Meanwhile, Sanxiapeptin could influence the cell wall permeability and integrity by increasing the activities of chitinase and glucanase, resulting in abnormal chitin consumption and the decrease of glucan. Intriguingly, Sanxiapeptin could effectively control postharvest decay in citrus fruits, and activate the host resistance responses by regulating the phenylpropanoid pathway. In conclusion, Sanxiapeptin exhibits multiphasic antifungal mechanisms of action to control green mold in citrus fruits, shows great potential as novel food preservatives.

Correction of congenital auricle deformities with ear mould: A systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of ear moulds for congenital auricle deformities. METHODS: Databases including Medline, EMBASE, Cochrane Library, Chinese BioMedical Literature Database (CBM) and Web of Science were systematically reviewed. Randomised controlled trials (RCT), non-randomised control trials (non-RCT), quasi-randomised control trials (quasi-RCT) and self-controlled before-after trials were also included. Data extraction was independently conducted by two authors. The Risk Of Bias In Non-randomised Studies of Interventions (ROBIN-I) was used to evaluate the risk bias. Heterogeneity was assessed using I2 and chi-square tests. Effective rate, adverse reaction rate and their 95%CI were calculated. Funnel plots, Begg's test as well as sensitivity and subgroup analyses were performed. RESULTS: The analysis encompassed ten studies, comprising one RCT and nine self-controlled before-after trials, involving 1860 ears (1248 children). The pooled effective rate and adverse reaction rate of ear mould were 91% (95% CI: 0.87-0.94) and 9% (95%CI: 0.02-0.17), respectively. No serious adverse reactions were reported. The effective rate of ear mould intervention showed no significant difference between age at correction≤42 days group (90%, 95%CI: 0.85-0.94) and that >42 days group (93%, 95%CI: 0.83-0.99). Similarly, there was no statistical difference in the correction efficiency between duration of wearing ear mould≤30 days group (90%, 95%CI: 0.85-0.94) and that >30 days group (92%, 95%CI: 0.86-0.96). The effective rate for correcting cryptotia ear (98%, P < 0.001), cup ear (93%, P = 0.004) and prominent ear (90%, P = 0.014) was higher than that of helical rim deformity (66%). CONCLUSIONS: In the short term, the use of ear moulds is effective and safe in correcting congenital auricle deformities. Notably, the correction efficacy for cryptotia, cup ear and prominent ear deformities surpasses that of helical rim deformities. However, further research is required to ascertain the impact of the duration of wearing on the correction of congenital auricle deformities.

Sweet triterpenoid glycoside from Cyclocarya paliurus ameliorates obesity-induced insulin resistance through inhibiting the TLR4/NF-κB/NLRP3 inflammatory pathway.

Our prophase studies have manifested that the sweet triterpenoid glycoside from the leaves of Cyclocarya paliurus (CPST) effectively improved the disorders of glucolipid metabolism in vitro and in patients. The current purpose was to further detect its mechanisms involved. The results demonstrated that CPST could ameliorate high-fat diet (HFD)-induced insulin resistance (IR), which was linked to reducing HFD-induced mice's body weight, serum glucose (GLUO), triglyceride (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C), lowering the area under the oral glucose tolerance curve and insulin tolerance, elevating the percentage of brown adipose, high-density lipoprotein cholesterol (HDL-C), reducing fat droplets of adipocytes in interscapular brown adipose tissue (iBAT) and cross-sectional area of adipocytes. Further studies manifested that CPST obviously downregulated TLR4, MyD88, NLRP3, ASC, caspase-1, cleased-caspase-1, IL-18, IL-1ß, TXNIP, and GSDMD protein expressions and p-NF-кB/NF-кB ratio in iBAT. These aforementioned findings demonstrated that CPST ameliorated HFD induced IR by regulating TLR4/NF-κB/NLRP3 signaling pathway, which in turn enhancing insulin sensitivity and glucose metabolism.

The inappropriate application of imidacloprid destroys the ability of predatory natural enemies to control pests in the food chain: A case study of the feeding behavior of Orius similis on Frankliniella occidentalis.

Insecticides are an indispensable and important tool for agricultural production. However, the inappropriate application of insecticides can cause damage to the food chain and ecosystem. Orius similis is an important predatory and natural enemy of Frankliniella occidentalis. Imidacloprid is widely used to control pests, but will inevitably exert adverse effects on O. similis. In order to determine the effect of different imidacloprid treatments on the ability of O. similis to prey on the 2nd-instar nymphs of F. occidentalis, we determined the toxicity and predation of imidacloprid on different stages of O. similis under contact and ingestion treatments. In addition, we used the Holling disc equation to evaluate the ability of O. similis to search and exhibit predatory activity following contact and ingestion treatments. Analysis showed that the highest LC10 and LC20 values for imidacloprid contact and ingestion toxicity treatment were 17.06 mg/L and 23.74 mg/L, respectively. Both imidacloprid treatments led toa reduction in the predatory of O. similis on prey. The functional responses of the 3rd to 5th instar nymphs, along with female and male O. similis adults to the 2nd-instar nymphs of F. occidentalis were consistent with the Holling type II response following contact and ingestion with imidacloprid. However, following imidacloprid treatment, the handing time (Th) of O. similis with single F. occidentalis was prolonged and the instantaneous attack rate (a) was reduced after imidacloprid treatment. The predatory capacity (a/Th) of female O. similis adults when treated with the LC10 concentration of imidacloprid by ingestion was 52.85; this was lower than that of the LC10 concentration of imidacloprid in the contact treatment (57.67). The extent of predation of O. similis on the 2nd-instar nymphs of F. occidentalis was positively correlated with prey density, although the search effect was negatively correlated with prey density. The most extensive search effect was exhibited by adult O. similis females. Simulations with the Hessell-Varley interference model showed that an increase in the number of O. similis would reduce search efficiency regardless of whether they were treated with imidacloprid or not. Thus, O. similis, especially female adults, exhibited strong potential for controlling the 2nd-instar nymphs of F. occidentalis. The toxicity of ingestion following treatment with the same concentration of imidacloprid in O. similis was greater than that of contact treatment. When using O. similis to control F. occidentalis in the field, we should increase the number of female adults released, and prolong the interval between imidacloprid treatment and O. similis exposure. This strategy will improve the control ability of O. similis, coordinate both chemical and biological control, reduce the impact of pesticides on the environment, and improve the efficiency of agricultural production.

Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases.

Presenilin, a transmembrane protein primarily known for its role in Alzheimer's disease (AD) as part of the γ-secretase complex, has garnered increased attention due to its multifaceted functions in various cellular processes. Recent investigations have unveiled a plethora of functions beyond its amyloidogenic role. This review aims to provide a comprehensive overview of presenilin's diverse roles in AD and other neurodegenerative disorders. It includes a summary of well-known substrates of presenilin, such as its involvement in amyloid precursor protein (APP) processing and Notch signaling, along with other functions. Additionally, it highlights newly discovered functions, such as trafficking function, regulation of ferritin expression, apolipoprotein E (ApoE) secretion, the interaction of ApoE and presenilin, and the Aß42-to-Aß40-converting activity of ACE. This updated perspective underscores the evolving landscape of presenilin research, emphasizing its broader impact beyond established pathways. The incorporation of these novel findings accentuates the dynamic nature of presenilin's involvement in cellular processes, further advancing our comprehension of its multifaceted roles in neurodegenerative disorders. By synthesizing evidence from a range of studies, this review sheds light on the intricate web of presenilin functions and their implications in health and disease.

[Evolution and Application of Disease Control Priorities]. / ç–¾ç— æŽ§åˆ¶ä¼˜å ˆçš„æ¼”è¿›åŠåº”ç”¨.

Disease control priority (DCP) is an important public health intervention strategy. Diseases that should be prioritized for prevention and control are first screened with a series of criteria, including the severity of the disease burden, the effectiveness of disease control technologies, the prevention and control capacity of the existing health system, etc. Then, the prevention and control technologies for these diseases undergo qualitative evaluation (eg, face-to-face interviews, expert consultation, workshops, etc) and quantitative evaluation (eg, cost-benefit analysis, multi-criteria decision analysis, etc). Finally, the public health initiatives that should be prioritized are identified. From the conception of the idea, to the formal proposition of the concept, to guidance for practice, DCP has gone through more than 70 years of development. Through DCP, significant contributions has been made to improving the efficiency of health care service systems and promoting the health of populations in developing countries. Herein, we systematically reviewed the background, development history, realization method, and practical applications of DCP, focusing on exploring the application potential of DCP in health governance and providing technical support and decision-making reference for the comprehensive promotion of the Healthy China Initiative.

Secure image encryption algorithm using chaos-based block permutation and weighted bit planes chain diffusion.

Aiming at the problem of insufficient security of image encryption technology, a secure image encryption algorithm using chaos-based block permutation and weighted bit planes chain diffusion is proposed, which is based on a variant structure of classical permutation-diffusion. During the permutation phase, the encryption operations of dividing an image into sub-block, block scrambling, block rotation and block inversion, negative-positive transformation, color component shuffling are performed sequentially with chaotic sequences of plaintext association. In the chain diffusion stage, different encryption strategies are adopted for the high and low 4-bit planes according to the weight of image information. Theoretical analyses and empirical results substantiate that the algorithm conforms to the cryptographic requirements of confusion, diffusion, and avalanche effects, while possessing excellent numerical statistical properties with a large cryptographic space. Therefore, the cryptanalysis-propelled security enhancement mechanism proposed in this paper effectively amplifies the aptitude of the algorithm to withstand cryptographic attacks.

The inhibition of VDAC1 oligomerization promotes pigmentation through the CaMK-CRTCs/CREB-MITF pathway.

The voltage-dependent anion channel 1 (VDAC1) forms an oligomeric structure on the mitochondrial outer membrane, which plays critical roles in many physiological processes. Research studies have demonstrated that the knockout of VDAC1 increases pigment content and up-regulates the expression of melanogenic genes. Due to its involvement in various physiological processes, the depletion of VDAC1 has significant detrimental effects on cellular functions and the inhibition of VDAC1 oligomerization has recently emerged as a promising strategy for the treatment of several diseases. In this study, we found that VDAC1 oligomerization inhibitors, VBIT-12 and NSC-15364, promote melanogenesis, dendrite formation and melanosome transport in human epidermal melanocytes (HEMCs). Mechanistically, treatment of HEMCs with an oligomerization inhibitor increased the level of cytoplasmic calcium ions, which activated calcium-calmodulin dependent protein kinase (CaMK) and led to the phosphorylation of CREB and the nuclear translocation of CREB-regulated transcription coactivators (CRTCs). Subsequently, CRTCs, p-CREB and CREB-binding protein (CBP) in the nucleus cooperatively recruit the transcription machinery to initiate the transcription of MITF thus promoting pigmentation. Importantly, our study also demonstrates that VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants, highlighting their potential as a therapeutic strategy for skin pigmentation disorders.

Neoadjuvant chemotherapy is linked to an amended anti-tumorigenic microenvironment in gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a frequently intervention for patients with locally advanced gastric cancer (GC). Nevertheless, its impact on the tumor immune microenvironment remains unclear. METHODS: We used immunohistochemistry to identify T-cell subpopulations, tumor-associated neutrophils (TANs), and tumor-associated macrophages (TAMs) in the GC microenvironment (GCME) among paired samples (pre-chemotherapy and post-chemotherapy) from 48 NAC-treated patients. Multiplex immunofluorescence (mIF) was performed to assess immune biomarkers, including CK, CD4, CD8, FOXP3, PD1, PD-L1, CD163, CD86, myeloperoxidase and Arginase-1 in paired samples from 6 GC patients whose response to NAC were rigorously defined. RESULTS: NAC was intricately linked to enhanced CD8+:CD4+ ratio, reduced CD163+ M2-like macrophages, augmented CD86+ M1: CD163+ M2-like macrophage ratio, and diminished FOXP3+ regulatory T cells (T-regs) and TANs density. Based on mIF, PD1+CD8+T-cells, FOXP3+T-regs, PD-L1+ TANs, and CD163+ M2-like macrophages exhibited marked reduction and greater co-localization with tumor cells following NAC. The pre-NAC FOXP3+ T-regs and CD163+ M2-like macrophages content was substantially elevated in the response cohort, whereas, the post-NAC CD8+:CD4+ and CD86+ M1: CD163+ M2-like macrophage ratios were intricately linked to the tumor pathologic response. We observed greater CD163+ M2-like macrophages and tumor cells co-localization following NAC, which was correlated with tumor pathologic response. Lastly, multivariate analysis revealed that post-NAC CD8+:CD4+ and CD86+ M1: CD163+ M2-like macrophage ratios were stand-alone indicators of positive patient prognosis. CONCLUSIONS: NAC converts the GCME to an anti-tumorigenic state that is conducive to enhanced patient outcome. These finding can significantly benefit the future planning of highly efficacious and personalized GC immunotherapy.

Tribuloside acts on the PDE/cAMP/PKA pathway to enhance melanogenesis, melanocyte dendricity and melanosome transport.

ETHNOPHARMACOLOGICAL RELEVANCE: Tribuloside, a natural flavonoid extracted from Chinese medicine Tribulus terrestris L., has shown potent efficacy in treating various diseases. In China, the fruits of Tribulus terrestris L. have long been utilized for relieving headache, dizziness, itchiness, and vitiligo. Water-based extract derived from Tribulus terrestris L. can enhance melanogenesis in mouse hair follicle melanocytes by elevating the expression of α-melanocyte stimulating hormone (α-MSH) and melanocortin-1 recepter (MC-1R). Nevertheless, there is a lack of information regarding the impact of tribuloside on pigmentation in both laboratory settings and living organisms. AIM OF THE STUDY: The present research aimed to examine the impact of tribuloside on pigmentation, and delve into the underlying mechanism. MATERIALS AND METHODS: Following the administration of tribuloside in human epidermal melanocytes (HEMCs), we utilized microplate reader, Masson-Fontana ammoniacal silver stain, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to measure melanin contents, dendrite lengths, melanosome counts; L-DOPA oxidation assay to indicate tyrosinase activity, Western blotting to evaluate the expression of melanogenic and associated phosphodiesterase (PDE)/cyclic adenosine monophosphate (cAMP)/cyclic-AMP dependent protein kinase A (PKA) pathway proteins. A PDE-Glo assay to verify the inhibitory effect of tribuloside on PDE was also conducted. Additionally, we examined the impact of tribuloside on the pigmentation in both zebrafish model and human skin samples. RESULTS: Tribuloside had a notable impact on the production of melanin in melanocytes, zebrafish, and human skin samples. These functions might be attributed to the inhibitory effect of tribuloside on PDE, which could increase the intracellular level of cAMP to stimulate the phosphorylation of cAMP-response element binding (CREB). Once activated, it induced microphthalmia-associated transcription factor (MITF) expression and increased the expression of tyrosinase, Rab27a and cell division cycle protein 42 (Cdc42), ultimately facilitating melanogenesis, melanocyte dendricity, and melanin transport. CONCLUSION: Tribuloside acts on the PDE/cAMP/PKA pathway to enhance melanogenesis, melanocyte dendricity, and melanosome transport; meanwhile, tribuloside does not have any toxic effects on cells and may be introduced into clinical prescriptions to promote pigmentation.

Research progress of metabolomics in cervical cancer.

INTRODUCTION: Cervical cancer threatens women's health seriously. In recent years, the incidence of cervical cancer is on the rise, and the age of onset tends to be younger. Prevention, early diagnosis and specific treatment have become the main means to change the prognosis of cervical cancer patients. Metabolomics research can directly reflect the changes of biochemical processes and microenvironment in the body, which can provide a comprehensive understanding of the changes of metabolites in the process of disease occurrence and development, and provide new ways for the prevention and diagnosis of diseases. OBJECTIVES: The aim of this study is to review the metabolic changes in cervical cancer and the application of metabolomics in the diagnosis and treatment. METHODS: PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2022. RESULTS: With the emergence of metabolomics, metabolic regulation and cancer research are further becoming a focus of attention. By directly reflecting the changes in the microenvironment of the body, metabolomics research can provide a comprehensive understanding of the patterns of metabolites in the occurrence and development of diseases, thus providing new ideas for disease prevention and diagnosis. CONCLUSION: With the continuous, in-depth research on metabolomics research technology, it will bring more benefits in the screening, diagnosis and treatment of cervical cancer with its advantages of holistic and dynamic nature.

Meta analysis of ovulation induction effect and pregnancy outcome of acupuncture & moxibustion combined with clomiphene in patients with polycystic ovary syndrome.

Objective: Using Mesh Meta Analysis to evaluate the efficacy of Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene for treating Polycystic Ovary Syndrome (PCOS), in order to provide evidence-based medical evidence for whether to recommend Acupuncture & Moxibustion or Combine western medicine to treat PCOS. Methods: Eight databases including The Cochrane Library, Pubmed, Embase, Web of Science, CNKI, Wanfang Date, VIP and CBM were searched by computer. The included research period is from the establishment of the database to May 2023, which concerned with randomized controlled trials involving Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene on ovulation induction and pregnancy outcome in patients with PCOS. The duration of the research paper is from 2016 to 2023.The inclusion criteria refer to the Rotterdam standards issued by the European Center for Human Reproduction and Embryology and the American Society of Reproductive Medicine in January 2003, or the Expert Consensus on the Diagnosis and Treatment of Polycystic Ovarian Syndrome by the Endocrinology Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association. Simultaneously exclude related diseases, repetitive literature, as well as literature with incomplete abstract information and no original data provided. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias included in the study, using Stata17.0 software for a mesh meta-analysis. Results: Six randomized controlled trials were included, covering 1410 PCOS patients. Three interventions included Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene. Mesh Meta Analysis showed that in terms of improving ovulation rate, there was no statistical difference between Acupuncture & Moxibustion (A), Clomiphene (B), Clomiphene combined with Acupuncture & Moxibustion (C) (P>0.05).Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=0.15,95% CI (-0.51,0.80)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.60,95% CI (0.97,2.23)], Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.45,95% CI (0.91,1.99)]. In terms of pregnancy outcome, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.80,95% CI (-1.84,0.23)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=0.29,95% CI (-0.73,1.30)], and Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.09,95% CI (0.39,1.79)], The order of pregnancy rate from high to low is Acupuncture & Moxibustion combined with Clomiphene (C), Acupuncture & Moxibustion (A), Clomiphene (C).In terms of influencing endometrial thickness, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.84,95% CI (-1.87,0.19)], Acupuncture & Moxibustion (A) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=0.26,95% CI (-1.01,1.53)], Clomiphene (B) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=1.10,95% CI (0.36,1.84)], Acupuncture & Moxibustion combined with Clomiphene (C) has the best effect on improving endometrial thickness. In subgroup analysis, the effect of Acupuncture & Moxibustion treatment frequency on ovulation rate and pregnancy rate was not statistically significant. The combination of Acupuncture & Moxibustion, Electroacupuncture and warm Acupuncture & Moxibustion has no effect on the pregnancy rate, but the combination of Electroacupuncture and Clomiphene has the best effect on improving the ovulation rate. In the observation of adverse reactions, compared with clomiphene alone, Acupuncture & Moxibustion combined with Clomiphene can reduce the occurrence of Luteinized Unruptured Follicle Syndrome (LUFS) and Ovarian Hyperstimulation Syndrome (OHSS), and reduce the occurrence of physical adverse reactions such as nausea, vomiting, headache and dermatitis. Conclusion: Acupuncture & Moxibustion is effective in improving the ovulation promoting effect and pregnancy outcome of PCOS patients. The ovulation promoting effect of Acupuncture & Moxibustion or combined with Clomiphene is similar to that of Clomiphene alone, but Acupuncture & Moxibustion combined with Clomiphene has more advantages in improving the pregnancy rate of PCOS, and it also can reduce the adverse reactions of Clomiphene alone. Acupuncture & Moxibustion can be used as a recommended treatment for PCOS. More cases should also be included in the subgroup analysis to study the impact of Acupuncture & Moxibustion programs on clinical efficacy and further optimize the Acupuncture & Moxibustion treatment program. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier (CRD42023433057).