Unveiling the dynamics of gut microbial interactions: a review of dietary impact and precision nutrition in gastrointestinal health.

The human microbiome, a dynamic ecosystem within the gastrointestinal tract, plays a pivotal role in shaping overall health. This review delves into six interconnected sections, unraveling the intricate relationship between diet, gut microbiota, and their profound impact on human health. The dance of nutrients in the gut orchestrates a complex symphony, influencing digestive processes and susceptibility to gastrointestinal disorders. Emphasizing the bidirectional communication between the gut and the brain, the Brain-Gut Axis section highlights the crucial role of dietary choices in physical, mental, and emotional well-being. Autoimmune diseases, particularly those manifesting in the gastrointestinal tract, reveal the delicate balance disrupted by gut microbiome imbalances. Strategies for reconciling gut microbes through diets, precision nutrition, and clinical indications showcase promising avenues for managing gastrointestinal distress and revolutionizing healthcare. From the Low-FODMAP diet to neuro-gut interventions, these strategies provide a holistic understanding of the gut's dynamic world. Precision nutrition, as a groundbreaking discipline, holds transformative potential by tailoring dietary recommendations to individual gut microbiota compositions, reshaping the landscape of gastrointestinal health. Recent advancements in clinical indications, including exact probiotics, fecal microbiota transplantation, and neuro-gut interventions, signify a new era where the gut microbiome actively participates in therapeutic strategies. As the microbiome takes center stage in healthcare, a paradigm shift toward personalized and effective treatments for gastrointestinal disorders emerges, reflecting the symbiotic relationship between the human body and its microbial companions.

Genomic characterisation of multi-drug resistant Escherichia coli and Klebsiella pneumoniae co-harbouring mcr-1 and mcr-3 genes on a single plasmid from paediatric clinical cases.

OBJECTIVES: Emergence of the plasmid-born mobile colistin resistance (mcr) gene is a growing concern in healthcare. Therefore, this study aimed to genomically characterise multidrug-resistant Escherichia coli and Klebsiella pneumoniae co-harbouring the mcr-1 and mcr-3 genes in young children. METHODS: E. coli (n = 3) and K. pneumoniae (n = 2) were collected from abdominal secretions and blood, respectively. The isolates were screened using tryptone soy broth with 4 µL/mL polymyxin-B. Growing bacteria were identified using the VITEK-2 system, matrix-assisted laser desorption/ionisation time-of-flight, and 16s RNA sequencing, followed by antibiotic susceptibility testing. Metallo-ß-lactamase (MBL) and extended-spectrum ß-lactamase (ESBL) production was also detected. Afterwards, strains were subjected to molecular screening targeting mcr variants and ESBL/MBL-encoding genes. Conjugation, pulsed-field gel electrophoresis, Southern hybridisation, multilocus sequence typing, and phylogenic group detection were performed, along with plasmid-genome sequencing and bioinformatics analysis. RESULTS: E. coli isolates (EC-19-322, 323, and 331) and K. pneumoniae isolates (KP-19-225 and 226) harboured both mcr-1 and mcr-3 genes. These strains were also found to be resistant to more than three classes of antibiotics. The conjugation experiment revealed the presence of mcr-1 and mcr-3 on a single plasmid, and the transmission frequency was 10-2 to 10-3. Both strains were found to be able to produce ESBLs and MBL. E. coli EC-19-322 and 323 were identified as ST131(O25a:H41); SP-19-331, as ST1577 (O16:H30); and K. pneumoniae, as ST231 (K2). All E. coli strains belonged to phylogenetic group B2, and the results of pulsed-field gel electrophoresis supported the multilocus sequence typing findings. CONCLUSION: This study reported the co-occurrence of mcr-1 and mcr-3 genes on a single plasmid in pathogenic ESBL/MBL-producing E. coli and K. pneumoniae isolated from young children.

A growing battlefield in the war against biofilm-induced antimicrobial resistance: insights from reviews on antibiotic resistance.

Biofilms are a common survival strategy employed by bacteria in healthcare settings, which enhances their resistance to antimicrobial and biocidal agents making infections difficult to treat. Mechanisms of biofilm-induced antimicrobial resistance involve reduced penetration of antimicrobial agents, increased expression of efflux pumps, altered microbial physiology, and genetic changes in the bacterial population. Factors contributing to the formation of biofilms include nutrient availability, temperature, pH, surface properties, and microbial interactions. Biofilm-associated infections can have serious consequences for patient outcomes, and standard antimicrobial therapies are often ineffective against biofilm-associated bacteria, making diagnosis and treatment challenging. Novel strategies, including antibiotics combination therapies (such as daptomycin and vancomycin, colistin and azithromycin), biofilm-targeted agents (such as small molecules (LP3134, LP3145, LP4010, LP1062) target c-di-GMP), and immunomodulatory therapies (such as the anti-PcrV IgY antibodies which target Type IIIsecretion system), are being developed to combat biofilm-induced antimicrobial resistance. A multifaceted approach to diagnosis, treatment, and prevention is necessary to address this emerging problem in healthcare settings.

Diminishing Marginal Benefit of Social Distancing in Balancing COVID-19 Medical Demand-to-Supply

Social distancing has been adopted as a non-pharmaceutical intervention to prevent the COVID-19 pandemic from overwhelming the medical resources across the United States (US). The catastrophic socio-economic impacts of this intervention could outweigh its benefits if the timing and duration of implementation are left uncontrolled and ill-strategized. Here we investigate the dynamics of social distancing on age-stratified US population and benchmark its effectiveness in reducing the burden on hospital and ICU beds. Our findings highlight the diminishing marginal benefit of social distancing, characterized by a linear decrease in medical demands against an exponentially increasing social distancing duration. We determine an optimal intermittent social-to-no-distancing ratio of 5:1 corresponding to [~]80% reduction in healthcare demands - beyond this ratio, benefit of social distancing diminishes to a negligible level. COVID-19 Medical Demand Forecasthttps://eece.wustl.edu/chakrabarty-group/covid/

COVID-19 Progression Timeline and Effectiveness of Response-to-Spread Interventions across the United States

Motivated by the rapid upsurge of COVID-19 cases in the United States beginning March 2020, we forecast the disease spread and assess the effectiveness of containment strategies by using an estalished network-driven epidemic dynamic model. Our model is initialized using the daily counts of active and confirmed COVID-19 cases across the US. Based on our model predictions for the March 14-16 timeframe, the national epidemic peak could be expected to arrive by early June, corresponding to a daily active count of {approx} 7% of the US population, if no containment plans are implemented. Epidemic peaks are expected to arrive in the states of Washington and New York by May 21 and 25, respectively. With a modest 25% reduction in COVID-19 transmissibility via community-level interventions, the epidemic progression could be delayed by up to 34 days. Wholesale interstate traffic restriction is ineffective in delaying the epidemic outbreak, but it does desynchronize the arrival of state-wise epidemic peaks, which could potentially alleviate the burden on limited available medical resources. In addition to forecasting the arrival timeline of the state-wise epidemic peaks, we attempt at informing the optimal timing necessary to enforce community-level interventions. Our findings underscore the pressing need for preparedness and timely interventions in states with a large fraction of the vulnerable uninsured and liquid-asset-poverty populations. Forecast websitehttps://sites.google.com/view/covid19forecast

Effect of childhood neglect experience on cognitive flexibility / 中国学校卫生

Objective@#To understand cognitive flexibility among college students with childhood neglected experience, and to provide a thoretical basis and data reference for the study of cognitive characteristics of neglected people and its intervention.@*Methods@#A total of 719 college students were surveyed using the Childhood Neglect Scale, and were screened through Childhood Neglect Scale. Wisconsin Card Sorting Test (WCST) and Verbal Fluency Test(VFT)were adminstered among those with childhood neglect to understand the responding flexibility and spontaneous flexibility.@*Results@#The proportion of subjects with neglect experience was 43.74%. Boys,non-only children,students in rural areas neglect experience were higher(P<0.05). The neglect experience of childhood affects the individual’s response flexibility(t=2.22, P<0.05), as well as spontaneous flexibility(t=-2.17, P<0.05).@*Conclusion@#Childhood neglect experience has a negative impact on cognitive flexibility.

Effect of Xiao Jianzhongtang on AMPK/PGC1-α Signal Pathway in Skeletal Muscle of Exercise Fatigue Mice / 中国实验方剂学杂志

Objective:To observe the effect of Xiao Jianzhongtang on Adenylate-activated protein kinase/peroxidase proliferation-activated receptor coactivator 1-α （AMPK/PGC1-α） signaling pathway in skeletal muscle of exercise fatigue mice.Method:Forty Kunming mice were randomly divided into normal group， model group， Buzhong Yiqitang group and Xiao Jianzhongtang group， with 10 mice in each group. The model group， Buzhong Yiqitang group and Xiao Jianzhongtang group were trained on the treadmill to establish a fatigue model， and the normal group did not apply any intervention. At the same time as the treadmill training， the model group was given the same amount of normal saline. Xiao Jianzhongtang was administered with 5 g·kg-1 of medicine， and Buzhong Yiqitang was administered with 2.8 g·kg-1 of medicine for 6 days. After the experiment， the weight of each group of mice and the time of running out of exhaustion were measured，the colorimetric method was used to detect the serum urea （UREA）， lactate dehydrogenase （LDH）， muscle glycogen （MG）， and skeletal muscle of each group of mice Na+-K+-ATPase， Ca2+-Mg2+-ATPase content， pathological changes of skeletal muscle of each group were observed by hematoxylin-eosin （HE） staining， Western blot was used to detect the protein expression of AMPK and PGC1-α in skeletal muscle of each group .Result:Compared with normal group， the body weight of model group significantly decreased （P<0.01）， and the contents of Na+-K+-ATPase， Ca2+-Mg2+-ATPase， LDH， and MG significantly decreased （P<0.05，P<0.01）. The content of UREA increased significantly （P<0.01）， and the expression of AMPK and PGC1-α protein increased significantly （P<0.01）. Compared with model group， the mice in the Xiao Jianzhongtang group had significantly increased body weight （P<0.05）， significantly increased the time spent on treadmill exhaustion（P<0.01）， Na+-K+-ATPase， Ca2+-Mg2+-ATPase， LDH， and MG. The content increased significantly（P<0.05， P<0.01）， the content of UREA decreased significantly （P<0.01）， and the expression of AMPK and PGC1-α protein increased significantly （P<0.01）.Conclusion:Xiao Jianzhongtang has an anti-exercise fatigue effect， which may be related to enhancing skeletal muscle AMPK/PGC1-α pathway，enhancing mitochondrial oxidative phosphorylation，reducing accumulation of metabolites，slowing down glycogen consumption and decomposition，and enhancing skeletal muscle energy synthesis.

Protective Effect of Wutou Chishizhi Wan on Vascular Endothelial Cells and Oxidative Stress in Myocardial Ischemia-reperfusion Rats / 中国实验方剂学杂志

Objective:To investigate the protective effect of Wutou Chishizhi Wan on myocardial ischemia reperfusion injury （MIRI） in rats， and observe its effect on such mechanisms as coagulation function， vascular endothelial cells and oxidative stress in rats. Method:A total of 40 SD rats were randomly divided into normal group， model group， positive drug group （Urokinase group） and Wutou Chishizhi Wan group， with 10 rats in each group. Except for the normal group， rat myocardial ischemia-reperfusion injury models were established. The changes of heart rate （HR） at 10 min before ischemia， 30 min after ischemia and 30， 60， 120 min （T0，T1，T2，T3，T4）， and the change of electrocardiogram （ECG） J point after modeling in rats were observed. The pathological changes of rat myocardial tissue were observed by hematoxylin-eosin （HE） staining. The changes of four indexes of coagulation ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， fibrinogen content decreased significantly （FIB）］ in rats were observed. The contents of endothelin-1 （ET-1）， thromboxane A2 （TXA2） and prostacyclin （PGI2） in serum and myocardium levels of superoxide dismutase （SOD）， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） of MIRI rats were observed. Western blot assay was used for the detection of oxidative stress protein Keap1 and transcription factor-E2-related factor （Nrf2） expression levels in rat myocardial tissue. Result:Compared with the normal group， the ECG of MIRI rats showed significant myocardial ischemic injury-like changes， ST segment was significantly elevated， J point was significantly increased， and the incidences of HR in T1， T2， T3 and T4 were significantly reduced （P<0.05， P<0.01）. Compared with the model group， Wutou Chishizhi Wan significantly reduced ECG J-point changes in MIRI rats， while increased the incidence of HR in T1， T2， T3 and T4 （P<0.05， P<0.01）. Compared with the normal group， PT， APTT and TT in the model group were significantly shortened （P<0.01）， FIB content was significantly increased （P<0.01）， and the serum PGI2 level decreased and TXA2 and ET-1 levels increased significantly in the model group （P<0.01）. SOD content and GSH-Px activities of myocardial tissue in the model group were significantly reduced （P<0.01）， whereas the MDA content was increased （P<0.01）. Compared with the model group， PT of the Wutou Chishizhi Wan group was prolonged （P<0.05） and APTT slightly prolonged， TT significantly prolonged （P<0.01）， FIB content decreased （P<0.05）， serum PGI2 increased （P<0.05）， TXA2 and ET-1 decreased significantly in the Wutou Chishizhi Wan group （P<0.01）， myocardial MDA content decreased， and SOD content and GSP-Px activity increased significantly （P<0.01）. Meanwhile， the Wutou Chishizhi Wan group was able to activate the Keap1/Nrf2 signaling pathway， which significantly increased Nrf2 expression and significantly decreased Keap1 expression （P<0.01）. Conclusion:Wutou Chishizhi Wan group can protect myocardial injury in MIRI rats. The specific mechanism is to protect MIRI by regulating vascular endothelial cell homeostasis and oxidative stress levels and activating Keap1/Nrf2 signaling pathway.

Effects of RNA interference targeting the chemokine receptor 7 gene on the invasion and migration of the human melanoma cell line M14 / 中华皮肤科杂志

Objective To explore the effects of targeted silencing of the chemokine receptor 7 (CXCR7)gene on the invasion and migration of the melanoma cell line M14. Methods Western-blot analysis was performed to determine the protein expression of CXCR7 in melanoma cell lines M14 and A375, and CXCR7-overexpressing M14 cells were used in this study. Cultured M14 cells were divided into three groups: experimental group transfected with a small interfering RNA(siRNA)targeting CXCR7(CXCR7-siRNA), negative control group transfected with a negative control siRNA, blank control group receiving no treatment. Real-time quantitative PCR and Western-blot analysis were conducted to determine the mRNA and protein expressions of CXCR7 respectively in M14 cells, Transwell chambers were used to evaluate the invasive activity of M14 cells, and wound healing assay to estimate the migratory activity of M14 cells. Results The experimental group showed significantly decreased mRNA and protein expressions of CXCR7 compared with the negative control group and blank control group (CXCR7 mRNA: 0.412 ± 0.023 vs. 1.211 ± 0.117 and 1.000 ± 0.102, F = 30.068, P = 0.001; CXCR7 protein: 0.144 ± 0.005 vs. 1 and 1.016 ± 0.004, F =11 485.5, P = 0.000). The number of M14 cells crossing the polycarbonate membrane per high-power field (× 200)was significantly smaller in the experimental group than in the negative control group and blank control group (20.617 ± 1.503 vs. 42.000 ± 6.018 and 43.627 ± 2.152, F = 32.416, P = 0.001). Similarly, the number of migrating M14 cells in wound healing assay was significantly decreased in the experimental group compared with the negative control group and blank control group (15.00 ± 1.10 vs. 44.90 ± 2.20 and 45.30 ± 2.30, F = 2 411.945, P = 0.000). Conclusion Targeted silencing of the CXCR7 gene can significantly inhibit the invasion and migration of M14 cells in vitro, which may provide a potential target for the treatment of cutaneous melanoma.

Prevalence of sexually transmitted diseases among men who have sex with men in some cities of Jiangsu province / 中华皮肤科杂志

Objective To estimate the prevalence of sexually transmitted diseases(STDs) among men who have sex with men (MSM) in some cities of Jiangsu province.Methods A cross-sectional questionnaire survey was carried out among MSM attending gay bars in some cities of Jiangsu province.Participants underwent screening for STDs in accordance with their personal wishes.Urethral swabs,first void urine and blood samples were collected at these survey sites and delivered to the STD research laboratory for testing.Univariate analysis and multivariate logistic regression analysis were performed to assess factors associated with STDs.Results A total of 388 subjects completed the questionnaire and underwent physical examination and STD screening.Of these subjects,45.6％ had only homosexual behavior.Examination of urine or urethral swab specimens showed that the prevalence rate was 1.3％ (5/388),9.4％ (36/385),17.2％ (66/384) and 28.1％ (109/388) for Neisseda gonorrhoeae,Chlamydia trachomatis,Mycoplasma genitalium and Ureaplasma urealyticum infection respectively.Serological tests revealed that the positivity rate was 1.0％ (4/388) for anti-human immunodeficiency virus (HIV)antibody,18.8％(73/388) for Treponema pallidum particle agglutination assay (TPPA),12.1％(47/388) for rapid plasma reagin (RPR) test,9.8％ (38/388) for human herpes simplex virus (HSV)-2-IgG,9.8％ (38/388) for hepatitis B surface antigen,1.0％ (4/388) for anti-hepatitis C virus antibody and 2.1％ (8/388) for anti-hepatitis E virus antibody.Multivariate analysis indicated that Chlamydia trachomatis infection was independently and significantly associated with polymorphonuclear leucocyte (PMNL) counts in urethral swab smears (adjusted odds ratio (AOR):5.30,95％ CI:2.04-13.77,P ＜ 0.01),Mycoplasma genitalium infection was significantly associated with age (AOR:2.84,95％ CI:1.17-6.87,P＜ 0.05),PMNL counts in urethral swab smears (AOR:2.37,95％ CI:1.01-557,P＜ 0.05) and urethral discomfort in the past three months (AOR:2.43,95％ CI.1.18-5.02,P＜ 0.05),and syphilis (defined as a positive TPPA and RPR test) was associated with age (AOR:2.46,95％ CI:1.05-5.75,P ＜ 0.05) and seropositivity for anti-HSV-2 antibodies (AOR:3.70,95％ CI:1.62-8.44,P ＜ 0.01).Conclusions There is a high prevalence of STDs among MSM attending gay bars in some cities of Jiangsu province,with Chlamydia trachomatis and Mycoplasma genitalium as the most common pathogens of urethritis.

Clinical and pathological analysis of six cases of cutaneous leishmaniasis / 中华皮肤科杂志

Objective To analyze the epidemiological,clinical and histopathological characteristics of cutaneous leishmaniasis.Methods This study included six patients with cutaneous leishmaniasis diagnosed in the Institute of Dermatology,Chinese Academy of Medical Sciences and Peking Union Medical College,over the past 10 years.The epidemiological features as well as clinical and histopathologic presentations of these patients were analyzed retrospectively.Results All of the six patients were male.The mean age at onset of skin eruptions was 47.67 (range:37-67) years,and the mean duration of disease was 10 (range:6-18) months.Clinical presentations included erythema,nodules and ulcers in the face and limbs.Skin biopsy revealed infection-associated granulomatous inflammation with many amastigotes (basophilic bodies) in the cytoplasm of histiocytes,which were highlighted with Giemsa stain.All the patients had a history of working at or travel to epidemic areas.Conclusion The diagnosis of cutaneous leishmaniasis mainly depends on epidemiological data,clinical manifestation and histopathologic findings.

Expression and significance of CXCR7 chemokine receptor in cutaneous malignant tumors and their cell lines / 中华皮肤科杂志

Objective To investigate the expression of CXCR7 in several cutaneous malignant tumors including cutaneous squamous cell carcinoma (SCC),basal cell carcinoma (BCC) and invasive cutaneous malignant melanoma and their cell lines,as well as its significance.Methods Tissue specimens were obtained from the lesions of 30 patients with cutaneous squamous cell carcinoma,25 patients with basal cell carcinoma and 30 patients with cutaneous malignant melanoma.Immunohistochemistry was performed to detect the expression of CXCR7 protein in these tissue specimens and several cell lines (A375 human melanoma cells,M14 human melanoma cells,A431 human epidermoid carcinoma cells,HaCaT human keratinocytes).The mRNA expression of CXCR7 in these cell lines was measured by reverse transcription PCR.Results CXCR7 protein was apparently expressed in invasive cutaneous malignant melanoma.The high expression rate of CXCR7 protein was significantly elevated in cutaneous malignant melanoma tissue specimens compared with SCC and BCC tissue specimens [80％ (24/30) vs.26.67％ (8/30) and 8％ (2/25),x2 =17.16,28.36,both P ＜ 0.05].CXCR7 mRNA was expressed in A375,M14 and A431 cells,but not in HaCaT cells,with the strongest expression observed in A375 cells.Immunohistochemistry revealed the expression of CXCR7 protein only in A375 cells.Conclusions CXCR7 is highly expressed in cutaneous malignant melanoma and A375 cells,which may be involved in the malignant invasion and metastasis of melanoma.

Large cell transformation of mycosis fungoides: a case report / 中华皮肤科杂志

The clinical course of mycosis fungoides is indolent except when large cell transformation occurs. Large cell transformation of MF is rare and easy to misdiagnose. A case of large cell transformation of mycosis fungoides is reported. A 40-year-old man presented with a 10-year history of pruritic erythema and papules in the trunk and extremities as well as a 5-month history of nodules on the nape of the neck.Histopathologically, the erythematous patch showed typical changes of mycosis fungoides, while the tumor cells were small and expressed CD3 and CD4, and only a small number of tumor cells expressed CD30. Pathological examination of nodular lesions revealed the infiltration of large pleomorphic lymphoid cells expressing CD3 and CD4 throughout the entire dermis. There was an epidermotropism of large cells, and about 40% of these cells expressed CD30. Based on the medical history and histological findings, the patient was diagnosed with large cell transformation of mycosis fungoides. The lesions improved markedly after 3-week treatment with oral acitretin (30 mg once daily), subcutaneous interferon-alpha (2 × 106 IU thrice a week) and local superficial X-ray irradiation for nodular lesions. Up to the time of this writing, the patient had been followed.

Clinical characteristics of patients with juvenile localized scleroderma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical characteristics of juvenile localized scleroderma (JLS).</p><p><b>METHODS</b>The clinical data of 100 outpatients with JLS who were admitted to PUMC Hospital from 2000 to 2008 were retrospectively analyzed.</p><p><b>RESULTS</b>Of a total of 100 cases, 51 (51%) were confirmed as linear scleroderma, 26 (26%) as plaque morphea, 26 (26%) as deep morphea, 12 (12%) as generalized morphea, and 15 (15%) as a mixed subtype. Nine patients (9%) had family histories of rheumatic or autoimmune diseases, while 16 (16%) might be triggered by unknown factors. Totally 84 patients underwent antinuclear antibody tests and 38 patients (45.2%) had positive results.</p><p><b>CONCLUSIONS</b>Linear scleroderma are the most frequent subtype of JLS. Localized scleroderma may be associated with some autoimmune-related causes.</p>