A multicenter, double-blind, randomized, parallel-group, active-controlled, phase 3 clinical trial to compare the effectiveness and safety of two botulinum toxin type A formulations for improving moderate to severe glabellar wrinkles in Asians.

Botulinum toxin type A (BoNT-A) was first isolated in 1946, and since then, several formulations have been developed and widely used to treat wrinkles by inducing muscle paralysis. This multicenter, double-blind, randomized, parallel-group, active-controlled phase 3 clinical trial was designed to evaluate the efficacy and safety of a newly developed BoNT-A formulation, BMI2006, in improving moderate to severe glabellar wrinkles and to compare with existing onabotulinumtoxin A (OBoNT) injections. A total of 276 subjects were enrolled and received 20 units of the randomized material, which was intramuscularly injected into five different locations on the forehead. The primary endpoint, assessed at 4 weeks, showed no statistically significant difference in the improvement rate of glabellar wrinkles between the two groups, with BMI2006 demonstrating non-inferiority to comparator BoNT-A. Secondary endpoints, evaluated by both treating investigators and independent investigators, also exhibited similar improvement rates throughout the study period. Both groups reported high levels of satisfaction with no statistical difference between the two groups. Safety evaluations indicated mild and transient adverse events, with no serious reactions observed. In conclusion, BMI2006 is an effective and safe BoNT-A for treating glabellar wrinkles with an expected duration of action between 8 and 12 weeks.

Baseline systolic blood pressure, hypertension history, and efficacy of remote ischemic conditioning.

OBJECTIVE: We performed a post hoc exploratory analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to determine whether hypertension history and baseline systolic blood pressure (SBP) affect the efficacy of remote ischemic conditioning (RIC). METHODS: Based on the full analysis set of RICAMIS, patients were divided into hypertension versus non-hypertension group, or <140 mmHg versus ≥140 mmHg group. Each group was further subdivided into RIC and control subgroups. The primary outcome was modified Rankin Scale (mRS) 0-1 at 90 days. Efficacy of RIC was compared among patients with hypertension versus nonhypertension history and SBP of <140 mmHg versus ≥140 mmHg. Furthermore, the interaction effect of treatment with hypertension and SBP was assessed. RESULTS: Compared with control group, RIC produced a significantly higher proportion of patients with excellent functional outcome in the nonhypertension group (RIC vs. control: 65.7% vs. 57.0%, OR 1.45, 95% CI 1.06-1.98; p = 0.02), but no significant difference was observed in the hypertension group (RIC vs. control: 69.1% vs. 65.2%, p = 0.17). Similar results were observed in SBP ≥140 mmHg group (RIC vs. control: 68.0% vs. 61.2%, p = 0.009) and SBP <140 mmHg group (RIC vs. control: 65.6% vs. 64.7%, p = 0.77). No interaction effect of RIC on primary outcome was identified. INTERPRETATION: Hypertension and baseline SBP did not affect the neuroprotective effect of RIC, but they were associated with higher probability of excellent functional outcome in patients with acute moderate ischemic stroke who received RIC treatment.

A dynamic online nomogram for predicting renal outcomes of idiopathic membranous nephropathy.

BACKGROUND: Because spontaneous remission is common in IMN, and there are adverse effects of immunosuppressive therapy, it is important to assess the risk of progressive loss of renal function before deciding whether and when to initiate immunosuppressive therapy. Therefore, this study aimed to establish a risk prediction model to predict patient prognosis and treatment response to help clinicians evaluate patient prognosis and decide on the best treatment regimen. METHODS: From September 2019 to December 2020, a total of 232 newly diagnosed IMN patients from three hospitals in Liaoning Province were enrolled. Logistic regression analysis selected the risk factors affecting the prognosis, and a dynamic online nomogram prognostic model was constructed based on extreme gradient boost, random forest, logistic regression machine learning algorithms. Receiver operating characteristic and calibration curves and decision curve analysis were utilized to assess the performance and clinical utility of the developed model. RESULTS: A total of 130 patients were in the training cohort and 102 patients in the validation cohort. Logistic regression analysis identified four risk factors: course ≥ 6 months, UTP, D-dimer and sPLA2R-Ab. The random forest algorithm showed the best performance with the highest AUROC (0.869). The nomogram had excellent discrimination ability, calibration ability and clinical practicability in both the training cohort and the validation cohort. CONCLUSIONS: The dynamic online nomogram model can effectively assess the prognosis and treatment response of IMN patients. This will help clinicians assess the patient's prognosis more accurately, communicate with the patient in advance, and jointly select the most appropriate treatment plan.

The Regulation of the Disease-Causing Gene FXN.

Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease caused in almost all patients by expanded guanine-adenine-adenine (GAA) trinucleotide repeats within intron 1 of the FXN gene. This results in a relative deficiency of frataxin, a small nucleus-encoded mitochondrial protein crucial for iron-sulfur cluster biogenesis. Currently, there is only one medication, omaveloxolone, available for FRDA patients, and it is limited to patients 16 years of age and older. This necessitates the development of new medications. Frataxin restoration is one of the main strategies in potential treatment options as it addresses the root cause of the disease. Comprehending the control of frataxin at the transcriptional, post-transcriptional, and post-translational stages could offer potential therapeutic approaches for addressing the illness. This review aims to provide a general overview of the regulation of frataxin and its implications for a possible therapeutic treatment of FRDA.

Photochemistry of plateau lake-derived dissolved organic matter: Reactive species generation and effects on 17ß-estradiol photodegradation.

Naturally strong ultraviolet irradiation at high altitudes causes photobleaching of plateau lake DOM (P-DOM) and affects its photochemical activity. However, the photoreactivity of P-DOM has remained unclear under natural photobleaching condition. Here, six P-DOM samples isolated from plateau lakes in Yunnan Province, China as well as two reference DOM as comparisons were used to explore the photogeneration of reactive species (RS) and their effects on 17ß-estradiol photodegradation. Compared with SRHA/SRFA, P-DOM has lower aromaticity, average molecular weight, and electron-donating capacity. The quantum yields of triplet state P-DOM (3P-DOM*), 1O2, and ∙OH produced in P-DOM solutions were greatly higher than those of reference DOM. The RS quantum yields had positive linear correlations with E2/E3 and SR, whereas were negatively linear correlated with SUVA25. Radical quenching experiments showed that 3P-DOM* was the prominent RS for 17ß-estradiol photodegradation, and its contribution exceeded 70% for each of P-DOM. 3P-DOM*-mediated photodegradation was mainly attributed to the electron-transfer reactions with an average second-order rate constant of 4.62 × 109 M-1s-1, indicating the strong photoreactivity towards 17ß-estradiol. These findings demonstrate that P-DOM is an efficient photosensitizer for RS production, among which 3P-DOM* may play an important role in enhanced photodegradation for organic micropollutants in plateau lake enriched with DOM.

Fluorescence immunosensor based on a specific monoclonal antibody for highly sensitive and rapid detection of gizzerosine in feed.

Gizzerosine is a biogenic amine produced in fish meal drying process and posted higher mortality due to gizzard erosion in poultry than histamine. However, it is difficult to obtain gizzerosine and achieve sensitive practical detection due to its simple structure. Herein, a monoclonal antibody (mAb) specific to gizzerosine was generated based on the new structural design and a fluorescence immunosensor for sensitive and on-site detection of gizzerosine in feed was first established. Molecular modeling of the three-dimensional (3D) structure and surface electrostatic potential of gizzerosine indicated that the carbonyl group of gizzerosine hapten might affect the important sites of antigen-antibody interactions. The proposed structure was used to obtain the sensitive and specific mAb with IC50 of 3.88 ng/mL in indirect competitive ELISA which was approximately 100-fold lower than that of direct competitive ELISA. Considering the practical application scenarios, a fluorescence immunosensor based on microporous dry method integrated with independent quality control line was established to improve detection stability. Under the optimum conditions, the proposed immunosensor showed a good linear relationship from 1.10 to 19.78 ng/mL and provided a low detection limit of 50 ng/g which was approximately 80-fold lower than the maximum recommended amount (0.4 mg/kg) of gizzerosine in feed. The recoveries of 6 kinds of feed ranged from 83.1 % to 114.3 %, which was in good consistence with that of UHPLC-MS/MS. Overall, this work provides a fast, cost-effective and reliable on-site tool for rapid screening of gizzerosine residues in feed samples.

Differentiation of Polygonatum Cyrtonema Hua from Different Geographical Origins by near-Infrared Spectroscopy with Chemometrics.

BACKGROUND: The identification of the geographical origin of Polygonatum cyrtonema Hua is of particular importance because the quality and market value of Polygonatum cyrtonema Hua from different production areas are highly variable due to differences in the growing environment and climatic conditions. OBJECTIVE: This study utilized near-infrared spectra (NIR) of Polygonatum cyrtonema Hua (n = 400) to develop qualitative models for effective differentiation of Polygonatum cyrtonema Hua from various regions. METHODS: The models were produced under different conditions to distinguish the origins distinctly. Ten pre-processing methods have been used to pre-process the original spectra (OS) and to select the most optimal spectral pre-processing method. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to determine appropriate models. For simplicity, the pretreated full spectrum was calculated by different wavelength selection methods, and the four most significant variables were selected as discriminant indicator variables. RESULTS: The results show that Polygonatum cyrtonema Hua from different regions can be effectively distinguished using spectra from a series of samples analyzed by OPLS-DA. The accuracy of the OPLS-DA model is also satisfactory, with a good differentiation rate. CONCLUSION: The study findings indicate the feasibility of using spectroscopy in combination with multivariate analysis to identify the geographical origins of Polygonatum cyrtonema Hua. HIGHLIGHTS: The utilization of near-infrared spectroscopy combined with chemometrics exhibits high efficacy in discerning the provenance of herbal medicines and foods, thereby facilitating quality assurance measures.

A Novel Inhibitor of Translation Initiation Factor eIF5B in Saccharomyces cerevisiae.

The eukaryotic translation initiation factor eIF5B is a bacterial IF2 ortholog that plays an important role in ribosome joining and stabilization of the initiator tRNA on the AUG start codon during the initiation of translation. We identified the fluorophenyl oxazole derivative 2,2-dibromo-1-(2-(4-fluorophenyl)benzo[d]oxazol-5-yl)ethanone quinolinol as an inhibitor of fungal protein synthesis using an in vitro translation assay in a fungal system. Mutants resistant to this compound were isolated in Saccharomyces cerevisiae and were demonstrated to contain amino acid substitutions in eIF5B that conferred the resistance. These results suggest that eIF5B is a target of potential antifungal compound and that mutation of eIF5B can confer resistance. Subsequent identification of 16 other mutants revealed that primary mutations clustered mainly on domain 2 of eIF5B and secondarily mainly on domain 4. Domain 2 has been implicated in the interaction with the small ribosomal subunit during initiation of translation. The tested translation inhibitor could act by weakening the functional contact between eIF5B and the ribosome complex. This data provides the basis for the development of a new family of antifungals.

Exploring the Link Between Autophagy-Lysosomal Dysfunction and Early Heterotopic Ossification in Tendons.

Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma-induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma-induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V-ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy-lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO.

The synergy effect of multi-country policy actions announced in reaction to global risk: A network structure perspective.

The policy actions of countries reflect adaptive responses of local components within the system to the dynamic global risk landscape. These responses can generate interactions and synergy effects on alleviating the evolution of global risks. Adopting a network perspective, the study proposes a theoretical framework that connects three structural characteristics of policy synergy, namely, synergy scale, alignment intensity, and timing synchronization. Focusing on the Covid-19 pandemic as a typical global risk context, the study finds that policy synergy with a larger scale, stronger alignment intensity, and more synchronized timing has a positive impact on mitigating global risks. The effect of alignment intensity is particularly pronounced when polycentric governance involves 20 countries facing severe risks, whereas the effect of timing synchronization is more significant when the multicenter group comprises more countries. Building upon the concept of an efficient scale of polycentric governance in various dimensions, this study develops a policy synergy index model. Through multiple empirical analyses, this study validates the causal relationship between policy synergy and the future evolution of global pandemic risk. Policymakers can leverage the dynamic changes in the policy synergy to predict future risk situations and implement well-rounded and appropriate policy actions, thereby enhancing the efficacy of the synergy effect of multi-country policy actions for risk governance.

The functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure.

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure, with noncoding RNAs exerting regulatory influence. However, the molecular function of circular RNAs (circRNAs) in the progression from cardiac hypertrophy to heart failure remains unclear. To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure, we construct a global triple network (microRNA, circRNA, and mRNA) based on the competitive endogenous RNA (ceRNA) theory. We observe that cardiac hypertrophy related circRNA (circRNA CHRC), within the ceRNA network, is down-regulated in both transverse aortic constriction (TAC) mice and Ang-II--treated primary mouse cardiomyocytes. Silencing circRNA CHRC increases cross-sectional cell area, atrial natriuretic peptide, and ß-myosin heavy chain levels in primary mouse cardiomyocytes. Further screening reveals that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro. Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p, while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC overexpression. In summary, circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi.

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.

A peptide derived from TID1S rescues frataxin deficiency and mitochondrial defects in FRDA cellular models.

Friedreich's ataxia (FRDA), the most common recessive inherited ataxia, results from homozygous guanine-adenine-adenine (GAA) repeat expansions in intron 1 of the FXN gene, which leads to the deficiency of frataxin, a mitochondrial protein essential for iron-sulphur cluster synthesis. The study of frataxin protein regulation might yield new approaches for FRDA treatment. Here, we report tumorous imaginal disc 1 (TID1), a mitochondrial J-protein cochaperone, as a binding partner of frataxin that negatively controls frataxin protein levels. TID1 interacts with frataxin both in vivo in mouse cortex and in vitro in cortical neurons. Acute and subacute depletion of frataxin using RNA interference markedly increases TID1 protein levels in multiple cell types. In addition, TID1 overexpression significantly increases frataxin precursor but decreases intermediate and mature frataxin levels in HEK293 cells. In primary cultured human skin fibroblasts, overexpression of TID1S results in decreased levels of mature frataxin and increased fragmentation of mitochondria. This effect is mediated by the last 6 amino acids of TID1S as a peptide made from this sequence rescues frataxin deficiency and mitochondrial defects in FRDA patient-derived cells. Our findings show that TID1 negatively modulates frataxin levels, and thereby suggests a novel therapeutic target for treating FRDA.

Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress.

Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.

Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review).

Breast cancer arises from the malignant transformation of mammary epithelial cells under the influence of various carcinogenic factors, leading to a gradual increase in its prevalence. This disease has become the leading cause of mortality among female malignancies, posing a significant threat to the health of women. The timely identification of breast cancer remains challenging, often resulting in diagnosis at the advanced stages of the disease. Conventional therapeutic approaches, such as surgical excision, chemotherapy and radiotherapy, exhibit limited efficacy in controlling the progression and metastasis of the disease. Regulated cell death (RCD), a process essential for physiological tissue cell renewal, occurs within the body independently of external influences. In the context of cancer, research on RCD primarily focuses on cuproptosis, ferroptosis and pyroptosis. Mounting evidence suggests a marked association between these specific forms of RCD, and the onset and progression of breast cancer. For example, a cuproptosis vector can effectively bind copper ions to induce cuproptosis in breast cancer cells, thereby hindering their proliferation. Additionally, the expression of ferroptosis­related genes can enhance the sensitivity of breast cancer cells to chemotherapy. Likewise, pyroptosis­related proteins not only participate in pyroptosis, but also regulate the tumor microenvironment, ultimately leading to the death of breast cancer cells. The present review discusses the unique regulatory mechanisms of cuproptosis, ferroptosis and pyroptosis in breast cancer, and the mechanisms through which they are affected by conventional cancer drugs. Furthermore, it provides a comprehensive overview of the significance of these forms of RCD in modulating the efficacy of chemotherapy and highlights their shared characteristics. This knowledge may provide novel avenues for both clinical interventions and fundamental research in the context of breast cancer.

Aerobic Exercise Attenuates Pressure Overload-Induced Myocardial Remodeling and Myocardial Inflammation via Upregulating miR-574-3p in Mice.

BACKGROUND: Exercise training can promote cardiac rehabilitation, thereby reducing cardiovascular disease mortality and hospitalization rates. MicroRNAs (miRs) are closely related to heart disease, among which miR-574-3p plays an important role in myocardial remodeling, but its role in exercise-mediated cardioprotection is still unclear. METHODS: A mouse myocardial hypertrophy model was established by transverse aortic coarctation, and a 4-week swimming exercise training was performed 1 week after the operation. After swimming training, echocardiography was used to evaluate cardiac function in mice, and histopathologic staining was used to detect cardiac hypertrophy, myocardial fibrosis, and cardiac inflammation. Quantitative real-time polymerase chain reaction was used to detect the expression levels of miR-574-3p and cardiac hypertrophy markers. Western blotting detected the IL-6 (interleukin-6)/JAK/STAT inflammatory signaling pathway. RESULTS: Echocardiography and histochemical staining found that aerobic exercise significantly improved pressure overload-induced myocardial hypertrophy (n=6), myocardial interstitial fibrosis (n=6), and cardiac inflammation (n=6). Quantitative real-time polymerase chain reaction detection showed that aerobic exercise upregulated the expression level of miR-574-3p (n=6). After specific knockdown of miR-574-3p in mouse hearts with adeno-associated virus 9 using cardiac troponin T promoter, we found that the protective effect of exercise training on the heart was significantly reversed. Echocardiography and histopathologic staining showed that inhibiting the expression of miR-574-3p could partially block the effects of aerobic exercise on cardiac function (n=6), cardiomyocyte cross-sectional area (n=6), and myocardial fibrosis (n=6). Western blotting and immunohistochemical staining showed that the inhibitory effects of aerobic exercise on the IL-6/JAK/STAT pathway and cardiac inflammation were partially abolished after miR-574-3p knockdown. Furthermore, we also found that miR-574-3p exerts cardioprotective effects in cardiomyocytes by targeting IL-6 (n=3). CONCLUSIONS: Aerobic exercise protects cardiac hypertrophy and inflammation induced by pressure overload by upregulating miR-574-3p and inhibiting the IL-6/JAK/STAT pathway.

Dyslipidemia and Efficacy of Remote Ischemic Conditioning in Acute Moderate Ischemic Stroke: A Post Hoc Analysis of the RICAMIS Study.

BACKGROUND: Ischemic conditioning-induced cardioprotection was attenuated by dyslipidemia in some animal and clinical studies, which is not investigated in patients with stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to investigate the association of dyslipidemia on admission with the efficacy of remote ischemic conditioning (RIC). METHODS AND RESULTS: In this analysis, eligible patients were divided into dyslipidemia and normal-lipid groups according to the levels of 4 blood lipid profiles (total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), which were further subdivided into RIC and control subgroups. We analyzed the differences in functional outcome between RIC and control subgroups in dyslipidemia and normal-lipid patients, respectively, and the interaction effects of RIC treatment with blood lipid levels were evaluated. Among 1776 patients from intention-to-treat analysis, 1419 patients with data of blood lipid profiles were included in the final analysis. A significantly higher proportion of modified Rankin Scale score 0 to 1 was identified in the RIC versus control subgroup across the normal-total cholesterol group (69.9% versus 63.5%; P=0.04), normal-triglycerides group (68.1% versus 60.5%; P=0.016), high-low-density lipoprotein cholesterol group (65.7% versus 57.7%; P=0.025), and normal-high-density lipoprotein cholesterol group (68.3% versus 60.5%; P=0.005). Similar statistical trends were found in the high-total cholesterol group (62.8% versus 55.5%; P=0.059), high-triglycerides group (67.8% versus 60.1%; P=0.099), normal-low-density lipoprotein cholesterol group (69.8% versus 63.7%; P=0.105), but no statistical significance was found in the low-high-density lipoprotein cholesterol group (63.4% versus 61%; P=0.705). Furthermore, no significant interaction effect of RIC intervention by blood lipid profiles was found. Similar results were obtained for lipids as continuous variables. CONCLUSIONS: Blood lipids on admission was not associated with the neuroprotective effect of RIC.

Different acupuncture and moxibustion therapies for mild cognitive impairment: a network meta-analysis.

OBJECTIVE: To investigate the effectiveness of different acupuncture and moxibustion therapies in improving cognitive function in patients with mild cognitive impairment (MCI) to determine the optimal approach. This study aims to provide insights into the treatment of MCI patients for future randomized controlled trials (RCTs) and clinical decision-making. MATERIALS AND METHODS: RCT studies were retrieved from databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, WANFANG, VIP, and SinoMed. The Cochrane risk of bias tool was used to assess the risk of bias for eligible trials. Bayesian network meta-analysis was conducted using R4.2.3 software. RESULTS: A total of 46 RCTs with 3641 participants were included. The network meta-analysis showed that acupoint pressing + cognitive training + auricular point sticking, massage + western medicine treatment, and electroacupuncture + western medicine treatment ranked first, second, and third in improving MMSE score, respectively. Acupoint pressing + cognitive training, cognitive training + scalp acupuncture, and cognitive training + moxibustion ranked first, second, and third in improving MoCA score, respectively. CONCLUSION: This study showed that acupoint pressing alone or acupoint pressing + auricular point sticking may improve cognitive function in MCI patients and possibly be the most effective acupuncture interventions for the treatment of MCI.

Correlation between the facial skin microbiome and sensitive skin using the 2bRAD-M technique.

OBJECTIVE: This study aimed to expound on the correlation between facial skin microbiome and sensitive skin (SS) using a novel sequencing technique. METHODS: We applied the 2bRAD sequencing for the microbiome, which enables accurate characterization of the low-biomass microbiome at species resolution to profile facial skin microbes in SS and non-SS groups. Further, the bacterial colonies were isolated and cultured from skin surfaces to study the pro-inflammatory effect on human keratinocytes by ELISA. RESULTS: We accordingly identified 1142 genera and 4436 strains. In the SS group, the proportions of Actinomyces and Microbotryomycetes were significantly increased, whereas that of Acidimicrobiia was decreased. Kruskal-Wallis analysis revealed significant differences in 11 genera and 35 species, among which the proportions of Dermabacter, Chryseobacterium, Rhodotorula and Peptoniphilus A were increased in the SS group. Analysis of the top 10 genera revealed increased proportions of Cutibacterium, Corynebacterium and Staphylococcus. Moreover, the proportion of Dermabacter hominis was significantly increased by 18.9-fold in the SS group, whereas those of many Streptococcus strains were significantly decreased. Focus on the isolated bacterial colonies from skin surfaces, more yellow colonies were found in SS group when cultured in Tryptic Soy Broth medium for 48 h, and more interleukin-8 was detected on keratinocytes after yellow colonies stimulation, such as S.capitis, M.luteus. CONCLUSIONS: This study suggests that more SS-associated microorganisms can be identified using the 2bRAD technique even with a small sample size. Dermabacter hominis and Chryseobacterium was firstly reported with a significantly increase in SS, and the S.capitis, as well as M.luteus, but not S.aureus, may be associated with skin inflammation.

OBJECTIF: Cette étude visait à expliquer la corrélation entre le microbiome de la peau du visage et la peau sensible (PS) à l'aide d'une nouvelle technique de séquençage. MÉTHODES: Nous avons appliqué le séquençage 2bRAD pour le microbiome, ce qui nous a permis de caractériser précisément le microbiome à faible biomasse à la résolution des espèces pour profiler les microbes de la peau du visage dans les groupes PS et non­PS. En outre, les colonies bactériennes ont été isolées et cultivées à partir de surfaces cutanées pour étudier l'effet pro­inflammatoire sur les kératinocytes humains par ELISA. RÉSULTATS: Nous avons donc identifié 1 142 genres et 4 436 souches. Dans le groupe PS, on a pu constater des proportions d'Actinomyces et de microbotryomycètes significativement accrues, pour de moindres proportions d'Acidimicrobiia. L'analyse de Kruskal­Wallis a révélé des différences significatives dans 11 genres et 35 espèces, parmi lesquelles des proportions de Dermabacter, Chryseobacterium, Rhodotorula et Peptoniphilus A accrues dans le groupe PS. L'analyse des 10 principaux genres a montré une augmentation des proportions de Cutibacterium, Corynebacterium et Staphylococcus. En outre, la proportion de Dermabacter hominis a été multipliée par 18,9 dans le groupe PS, soit une augmentation significative, tandis que celle de nombreuses souches de Streptococcus s'est avérée significativement plus basse. En se concentrant sur les colonies bactériennes isolées des surfaces cutanées, plus de colonies jaunes ont été trouvées dans le groupe PS lorsqu'elles étaient cultivées dans du milieu de bouillon trypticase soja pendant 48 h, et davantage d'interleukine­8 a été détectée sur les kératinocytes après la stimulation des colonies jaunes comme S. capitis, M. luteus. CONCLUSIONS: Cette étude suggère que davantage de micro­organismes associés au PS peuvent être identifiés à l'aide de la technique 2bRAD, même avec un échantillon de petite taille. Dermabacter hominis et Chryseobacterium ont été rapportés avec une augmentation significative pour les PS, et S. capitis, ainsi que M. luteus, mais pas S. aureus, pouvant être associés à une inflammation cutanée.