Evaluation of the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness

ABSTRACT Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo-pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months.

Chinese Medicines Treat Rheumatoid Arthritis via Gut-joint Axis： A Review / 中国实验方剂学杂志

Rheumatoid arthritis （RA） is a systemic autoimmune disease with local joint pain as the main clinical manifestation. It is one of the diseases specifically responding to traditional Chinese medicine （TCM）. The occurrence of RA is not only related to innate factors like genetic disorder but also associated with environmental factors， such as diets and microbial infection. The intestine， a vital human organ with digestive and immune functions， is a place where microorganisms colonize and exert intestinal metabolism-improving， barrier-protecting， and immunomodulatory effects. As the research on the onset and treatment of RA is deepening， the potential relationship of intestinal structural and functional abnormalities with the pathogenesis and progression of RA has been revealed. As clinical and experimental studies indicated， joint inflammation coexists with the impaired barrier function， imbalanced immune cells， and disordered gut microbiota. The theory of the gut-joint axis in the pathogenesis， progression， and treatment of RA is highly consistent with the holistic view in TCM. The recent pharmacological studies have shown that Chinese medicine prescriptions and active components can inhibit inflammation， protect joints， and maintain the intestinal function. This article summarizes the basic connotation of the gut-joint axis in RA and the mechanism by which TCM protect the intestinal barrier and modulate the immunity by regulating the gut microbiota structure and improving microbial metabolism in the treatment of RA. This review gives insights into the future research on the gut-joint axis in RA.

Biological Connotation of Pathogenesis of Colorectal Cancer Due to Damp-heat Accumulation Based on Immune Response-intestinal Microbial Axis / 中国实验方剂学杂志

Colorectal cancer （CRC） is a malignant tumor of the intestinal tract with changes in bowel habits， blood in the stool， and pain as the main clinical manifestations. With the change in lifestyle and diet structure in recent years， the incidence of CRC has been increasing year by year. The pathogenesis of CRC is closely related to abnormal immune response and chronic inflammation， intestinal microbial dysbiosis， and the production of oncogenic metabolites. There is a two-way communication between the intestinal microbiota and the body's immunity， which not only plays a key role in maintaining the body's health but also has a close relationship with the development of diseases. An increasing number of studies have shown that abnormal immune responses accelerate the disease process by producing inflammatory factors， causing chronic inflammation in the body， disrupting the intestinal mucosal barrier， and increasing mucosal permeability， thus resulting in dysbiosis of the intestinal microbial ecology and a large number of pathogenic microorganisms and their metabolites. In addition， dysbiosis of intestinal microbes， by suppressing the normal immune response， leads to the disruption of multiple metabolic pathways in the body， affecting the internal and external stress response of the intestine， inducing inflammation， and thus producing disease. Therefore， the complex crosstalk mechanism between the immune response and intestinal microbial axis is closely related to the development of CRC. Based on traditional Chinese medicine theory and clinical research， it was found that dietary factors are an important causative factor in the development of CRC. The deficiency of positive energy is the root cause of the disease， and damp-heat accumulation is the key pathogenesis. Through modern medical and biological research， it is believed that abnormal immune response is the microscopic manifestation of damp-heat entrapment， while intestinal microbial dysbiosis is the biological basis of toxic injection into the large intestine， and in the pathogenesis of CRC， the imbalance of immune response-intestinal microbial axis is compatible with damp-heat accumulation in traditional Chinese medicine. This study aims to explore the biological connotation of CRC due to damp-heat accumulation from the immune response-intestinal microbial axis， so as to interpret the pathogenesis of CRC due to damp-heat accumulation with objective data and provide new ideas and theoretical basis for the pathogenesis and treatment strategies of CRC due to damp-heat accumulation.

Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

Syndromes and Mechanisms of Depression Induced by Second Hit in Mice / 中国实验方剂学杂志

ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

CBCT analysis of the relative position between maxillary central incisors and alveolar bone in Southern Chinese adults / 口腔疾病防治

Objective@#Exploring the position and bone wall thickness characteristics of the maxillary central incisors in Southern Chinese adults to provide a clinical reference for the design of immediate maxillary central incisor implantation surgery.@*Methods@#The hospital ethics committee approved the study, and the patients provided informed consent. CBCT images of 990 adult patients (aged 20-79 years) from the Stomatology Hospital (January 2018 to December 2021) were categorized based on the dental arch form and age-sex groups. Sagittal CBCT images of the maxillary central incisors were used to measure the labial and palatal bone thickness wall at 4 mm the CEJ to apical, the middle of the root, and the angle between the tooth long axis and the long axis of the alveolar process, to compare the thickness of the labial and palatal bone walls in samples of male and female patients, and to explore the relationship between the angle between the tooth long axis and the alveolar process long axis in samples of male and female patients in different age groups (20-39 years; 40-59 years; 60-79 years).@*Results@#Significant differences were found in the labiopalatine side of the alveolar bone of the maxillary incisor root position. A total of 95.8% (948/990) of the maxillary incisors were positioned more buccally, 4.1% (41/990) were positioned more midway, and 0.1% (1/990) were positioned more palatally. The thicknesses of the bone wall at the CEJ of 4 mm below the palatal side, the middle of the root, and at the apex were greater (1.82 ± 0.56 mm, 3.20 ± 1.10 mm, and 7.70 ± 2.00 mm, respectively) than those at the labial side (1.21 ± 0.32 mm, 0.89 ± 0.35 mm, and 1.86 ± 0.82 mm, respectively), with statistical significance (P<0.05). Male bone wall thickness was generally greater than female bone wall thickness (P<0.05). The angle between the long axis of male teeth and the alveolar bone was 14.77° ± 5.66°, while that of female teeth was 12.80° ± 5.70°, with a statistically significant difference (P<0.05). The angle between the long axis of teeth and the alveolar bone in the 40-59-year-old group and the 60-79-year-old group was greater than that in the 20-39-year-old group, and the difference was statistically significant (P<0.05).@*Conclusion@#A total of 95.8% of adults in South China have maxillary central incisors with root deviation toward the labial bone cortex. The thickness of the labial bone wall is much thinner than that of the labial bone wall, which is the middle of the thickness of the root. In Southern Chinese adults, the angle between the upper central incisor and the long axis of the alveolar bone in males is greater than that in females, and the degree of the angle increases with age. It is recommended to pay attention to the thickness of the bone wall around the root and the angle between the teeth before immediate implantation surgery to choose a reasonable implantation plan.

Analysis of ocular biometric parameters in Tibetan patients with age-related cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To compare the differences of ocular biometric parameters of age-related cataract between Tibetan and Han ethnic groups, and to analyze the distribution characteristics of ocular biometric parameters in Tibetan cataract patients.METHODS:Retrospective cohort study. A total of 661 patients(1 030 eyes)with age-related cataract confirmed in the hospital between January 2019 and December 2020 were enrolled. The parameters of axial length, anterior chamber depth, keratometry, corneal astigmatism and astigmatic axis were measured by IOL Master 500 in 483 cases(739 eyes)of Tibetan age-related cataract patients and 178 cases(291 eyes)of Han patients.RESULTS:The axial length, anterior chamber depth and corneal astigmatism of the Tibetan patients with age-related cataract were 23.33(22.81, 23.86)mm, 3.04(2.79, 3.30)mm and 0.73(0.47, 1.07)D. The mean keratometry was 43.89±1.35 D. The results indicated that Tibetan cataract patients had shorter axial lengths and smaller keratometry compared to Han patients(all P&#x003C;0.05). Age in Tibetan patients was negatively correlated with axial length and anterior chamber depth, and positively correlated with keratometry(all P&#x003C;0.05). Tibetan male patients had longer axial lengths, deeper anterior chambers, and flatter corneas compared to female patients(all P&#x003C;0.05).CONCLUSION:There were differences in ocular biometric parameters between age-related cataract patients of Tibetan and Han ethnicities. The distribution of ocular biometric parameters in Tibetan cataract patients varied across different age groups and gender groups.

Traditional Chinese Medicine and Its Effective Components in Treating Alzheimer's Disease： A Review / 中国实验方剂学杂志

Alzheimer's disease is a common central neurodegenerative disease， mainly manifested by cognitive impairment and non-cognitive neuropsychiatric symptoms that severely affect patients' daily life and behavioral functioning. The pathogenesis of Alzheimer's disease is still unclear， and the western medicine currently used to treat Alzheimer's disease is only symptomatic， with a single pathway， limited efficacy， and many side effects. In recent years， with the deepening of research on Alzheimer's disease， the study and application of traditional Chinese medicine （TCM） in the treatment of Alzheimer's disease have gradually increased. Several studies have shown that TCM and its effective components can exert anti-Alzheimer's disease effects by regulating molecular mechanisms such as pathological protein production and aggregation， oxidative stress， neuroinflammation， ferroptosis， mitochondrial dysfunction， neurogenesis and neurotransmission， and brain-gut axis. This paper summarized the research progress of TCM in the treatment of Alzheimer's disease in recent years， so as to provide a reference for further study of the specific mechanism of TCM in the prevention and treatment of Alzheimer's disease and the discovery of effective components of TCM.

Biological Basis of Premature Ejaculation Based on Theory of "Brain-heart-kidney-semen Chamber" Axis / 中国实验方剂学杂志

The theory of "brain-heart-kidney-semen chamber" axis is proposed based on the basic theories of traditional Chinese medicine， the modern physiological characteristics of men's diseases， and clinical practice. According to this theory， dysfunctions of the brain， heart， kidney， and semen chamber are the core mechanisms for the occurrence of premature ejaculation， and the loss of control of the opening and closing of the seminal orifices due to the dysfunction of the semen chamber is the final link in the occurrence of premature ejaculation. The treatment of premature ejaculation based on the theory of "brain-heart-kidney-essence chamber" axis highlights the overall regulation of the Zang-fu organs involved in the disease， while focusing on the simultaneous treatment of the mind and body. By exploring the biological basis of the "brain-heart-kidney-essence chamber" axis and premature ejaculation， we propose that the biological basis of premature ejaculation and the axis is mainly related to the function decline of the local brain area， neuromodulation malfunction， central neurotransmitter imbalance， endocrine disorders， and enhanced sensory afferents of the penis. This study aims at providing a new approach for the prevention and treatment of premature ejaculation by traditional Chinese medicine and a scientific basis for the development of more effective therapeutic methods.

The Significant Roles of Gut-lung Microbiota in Shaping and Regulating Immunity / 中山大学学报(医学科学版)

The interaction between microbes and the human immune system has long been a focus in biomedical research. Next-generation sequencing has revealed that in addition to gut microbiota， the respiratory tract also harbors microbial communities， forming an interconnected network with the gut microbiota through immune cells and active factors. This review aims to explore how the gut and lung microbiota regulate immune responses， including their roles in local and systemic immune modulation. It also delineates the immunological connections along the gut-lung axis. Further elucidating the influence of microbes on the immune system holds important clinical significance for understanding diseases and exploring novel diagnostic and therapeutic strategies.

Effect of Raw and Processed Aurantii Fructus Immaturus Switched to Zhishi Shaoyaosan on Function of Brain-Gut-Microbiota Axis in Rats with Constipation-predominant Irritable Bowel Syndrome / 中国实验方剂学杂志

ObjectiveTo research the mechanism underlying the effect of raw and processed Aurantii Fructus Immaturus switched to Zhishi Shaoyaosan （ZSS） on constipation-predominant irritable bowel syndrome （C-IBS） rats via the brain-gut-microbiota axis. MethodEighty rats were randomly divided into the blank， model， positive drug （pinaverium bromide， 15.625 mg·kg-1）， raw ZSS， stir-fried ZSS， bran-fried ZSS， charcoal-fried ZSS and finished ZSS groups （3.75 g·kg-1）， with 10 rats in each group. Except for the blank group， which received intragastric administration of 0.9% sodium chloride solution at room temperature， all other groups were administered the ice solution at 0 to 4 ℃ （2 mL·d-1， for a total of 14 d） to establish the C-IBS rat model. The fecal water content and the propulsion rate of small intestine were detected after 14 d of continuous drug administration. The levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， neuro-peptide Y （NPY）， calcitonin gene-related peptide （CGRP）， substance P （SP）， diamine oxidase （DAO） and D-lactic acid （D-LA） were detected by enzyme linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the changes in colonic pathological injury in each group. The expression levels of cyclic adenosine monophosphate （cAMP）， protein kinase A （PKA） and aquaporin-3 （AQP3） mRNA in colon tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and the protein expressions of VIP and AQP3 in colon tissues were detected by Western blot. The content of short chain fatty acids （SCFAs） was determined by gas chromatography-mass spectrometry. ResultCompared with the blank group， the fecal water content and intestinal propulsion rate of rat in the model group were significantly decreased （P<0.01）， and the levels of 5-HT， VIP， CGRP and SP in serum were significantly increased. Simultaneously， the NPY levels significantly decreased （P<0.01）， the levels of DAO and D-LA in plasma were significantly increased （P<0.01）， and the mucosal epithelium of colon tissue was slightly damaged， with reduced goblet cells and significantly reduced luminal granules. The mRNA expression levels of AQP3， cAMP and PKA and the protein expression levels of AQP3 and VIP in colon tissue were significantly decreased （P<0.05， P<0.01）. The total amount of SCFAs in feces showed an obvious decreasing trend， with the contents of acetic acid， isobutyric acid， isovaleric acid， valeric acid and caproic acid decreased significantly， while the contents of propionic acid and butyric acid increased significantly （P<0.05， P<0.01）. Compared with the model group， the treatment groups increased the intestinal propulsion rate， improved the intestinal mucosal barrier function， and adjusted the level of serum brain-gut peptide in C-IBS rats （P<0.05， P<0.01）. The expression levels of AQP3， cAMP， PKA mRNA and VIP， AQP3 protein in colon tissue of rats in all treatment groups were increased. All the treatment groups had a significant downregulation of the content of SCFAs except for isobutyric acid in rat feces， and the effect of ZSS prepared by the bran-fried Aurantii Fructus Immaturus was superior than that of other ZSS. ConclusionThe raw and processed Aurantii Fructus Immaturus switched to ZSS could influence the brain-gut-microbiota axis to treat C-IBS rats and it is more reasonable to use bran-fried Aurantii Fructus Immaturus in ZSS.

Traditional Chinese Medicine in Treatment of Constipation Based on 5-HT Signaling Pathway： A Review / 中国实验方剂学杂志

Chronic constipation （CC） is one of the most common functional gastrointestinal diseases. At present， the overall therapeutic effect of CC is still not satisfactory worldwide， which seriously affects the quality of life and social function of patients. The etiology and pathophysiological mechanism of constipation are still unclear. It involves comprehensive factors such as heredity， social psychology， diet， intestinal flora imbalance， intestinal motility disorder， visceral sensitivity change， pelvic floor muscle group dysfunction and enteric nervous system （ENS） disorder. Among them， the abnormal factors of the brain-gut-microbiome axis are particularly significant. The brain-gut-microbiome axis is a complex network of interactions between the intestine and the brain， integrating and coordinating the physiological functions and pathological processes of the gastrointestinal tract. Microorganisms in the intestinal lumen play an important role in it， and can communicate with the intestinal tract and the central nervous system through nerve， endocrine and immune pathways. As a key brain-gut peptide in the regulation pathway of the brain-gut-microbiome axis， 5-hydroxytryptamine （5-HT） is involved in the regulation of gastrointestinal motility， sensation and secretion. The abnormal conduction of the 5-HT signaling pathway is closely related to the occurrence and development of constipation. Traditional Chinese medicine（TCM） is a unique precious resource in China， which has good curative effects and safety. In recent years， it has received extensive attention in the treatment of constipation. TCM and active ingredients， acupuncture and massage specifically regulate 5-HT signal transmission， so that the expressions of related molecules tend to be suitable for individual disease state levels to effectively improve constipation symptoms， with unique advantages. Therefore， this study used ''constipation''， ''intestinal flora''， ''5-HT''， and ''traditional Chinese medicine'' as the keywords to search PubMed， China National Knowledge Infrastructure （CNKI） and other literature databases. The correlation between 5-HT and constipation as well as brain-gut-microbiome axis and the research progress of TCM intervention in the 5-HT signaling pathway in the treatment of constipation were reviewed in order to explore the potential therapeutic value of 5-HT system in this disease and provide references for subsequent research.

Moderating effect of salidroside on intestinal microbiota in mice exposed to PM2.5 / 环境与职业医学

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM2.5 group, and an SAL+PM2.5 group, each containing 10 mice. In the SAL group and the SAL+PM2.5 group, the mice were administered SAL (60 mg·kg−1) by gavage, while in the control group and the PM2.5 group, sterile saline (10 mL·kg−1) was administered by gavage. In the PM2.5 group and the SAL+PM2.5 group, PM2.5 suspension (8 mg·kg−1) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg−1) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM2.5 group, and finally, the three groups clustered with the PM2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased. Compared to the control group, the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM2.5 group, the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM2.5 group (P<0.05). Conclusion Exposure to PM2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Slit-lamp assisted TORic Marker (STORM): A novel corneal axis marker

Background: Toric Intraocular lenses (IOLs) are supposed to be aligned at a particular axis for spectacle?free vision for distance. The evolution of topographers and optical biometers has made it quite achievable for us to aim the target. However, the result sometimes remains unpredictable. A big aspect of this depends on the preop axis marking for toric IOL alignment. Errors in axis marking have been reduced recently with the array of different toric markers in the market, but still we see postoperative refractive surprises due to faulty marking. Purpose: In this video, we present a novel slit lamp–based toric marker innovation, STORM, which gives us a hands?free approach to a reliable and accurate axis marking on the cornea. The axis marker is a simple modification to our age?old marker, with the advantage of no touch and slit?lamp assistance, which will make it error free and easy to use. Synopsis: The present innovation answers the problem statement of stable, economical, and accurate marking solution. Many a times, hand?holding devices create inaccurate and stressed condition while marking the cornea before corneal surgery. Highlights: The invention can be used for marking of accurate and easy astigmatic axis of a toric IOL preoperatively, that is, before the surgery. If the appropriate device is used to mark the cornea, it would impact the outcome of surgery. This device also makes the patient and the surgeon comfortable to mark the cornea with accuracy and without hesitation

Evaluation of 18FDG PET-CT-positive mediastinal-hilar lymph nodes in extrathoracic malignancies by EBUS-TBNA; correlation of SUVmax, and short-axis diameter with the final diagnosis

Introduction: Intrathoracic lymph node metastasis from extrathoracic neoplasms are rare. Primary malignancies that metastasize to mediastinal-hilar lymph nodes are head and neck , carcinoma breast ,and genitourinary. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)/endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently the preferred modality for mediastinal lymph node sampling. Methods: Fifty seven patients with extrathoracic malignancies with maximum standardized uptake value (SUVmax) of mediastinal-hilar lymph nodes greater than or equal to 2.5 were taken up for EBUS-TBNA. The histo-cytopathological results obtained from EBUS-TBNA were compared with SUVmax value and short-axis diameter of a lymph node as noted on EBUS. Results: Out of 74 sampled nodes, 49 (66.2%) were benign and 25 (33.8%) were malignant. The SUVmax range of benign nodes was 2.8� as compared to 3� of malignant nodes. The size range of malignant and benign nodes were 8� mm and 8� mm, respectively. The mean size of abnormal nodes (metastatic + granulomatous) was 17.5 (8� mm) and the mean SUVmax was 9.1 (3.4�), and it was a statistically significant difference when compared to reactive (normal) nodes. At SUVmax cut-off 7.5, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were 78.5%, 81.2%, 84.6%, and 74.2%, respectively for detecting abnormal nodes. At 13 mm size cut-off, sensitivity, specificity, PPV, NPV were 75.5%, 65%, 75%, and 72%, respectively, for detecting abnormal nodes. Conclusion: The majority of mediastinal-hilar nodes with increased metabolic activity are benign in nature. Size and SUVmax are poor predictors of metastasis in tuberculosis endemic region. There should be a restrictive attitude toward invasive diagnostic testing for mediastinal-hilar nodes in extrathoracic malignancies.

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

A Deep Insight into the Correlation Between Gut Dysbiosis and Alzheimer’s Amyloidopathy

Recent research has shown a strong correlation between gut dysbiosis and Alzheimer’s disease (AD). The purpose of this review is to investigate the relationship between gut dysbiosis, immune system activation, and the onset of AD and to examine current breakthroughs in microbiota-targeted AD therapeutics. A review of scientific literature was conducted to assess the correlation between gut dysbiosis and AD and the various factors associated. Gut dysbiosis produces an increase in harmful substances, such as bacterial amyloids, which makes the gut barrier and blood-brain barrier more permeable. This leads to the stimulation of immunological responses and an increase in cytokines such as interleukin-1? (IL-1?). As a result, gut dysbiosis accelerates the progression of AD. The review highlights the connection between gut dysbiosis and AD and the potential for microbiota-targeted therapies in AD treatment.

Serum Occludin and Zonulin Levels in Children With Attention-Deficit/Hyperactivity Disorder and Healthy Controls

Objective: To evaluate zonulin and occludin levels, potentially associated with immunological pathways in the gut-brain axis, in children with attention-deficit/hyperactivity disorder (ADHD). Method: We examined the association between serum levels of zonulin and occluding, and behavioral/emotional problems in children with ADHD. 40 medicationnaïve children meeting Diagnostic and statistical (DSM-5) criteria for ADHD (11 females; mean (SD) age 9.4 (1.6) years) and 39 healthy comparisons (12 females; mean (SD) age 9.3 (1.9) years) were studied. Serum zonulin and occludin levels were measured by (ELISA). Result: We found higher mean (SD) serum zonulin levels [37.1 (28.2) vs 8.1 (4.5) ng/mL; P<0.001) and occludin levels [2.4 (1.6) vs 0.6 (0.4) ng/mL; P<0.001] in the ADHD group compared to control group. Serum zonulin levels had a positive correlation with weight (r=0.452; P=0.003) and BMI (r=0.401; P=0.01) among children with ADHD. Serum zonulin and occludin levels also had a positive correlation with Conners parent rating scale scores (r=0.58; P<0.001), and Strengths and difficulties questionnaire scores (r=0.49; P<0.001). Multiple linear regression analysis revealed that age, sex, weight, conduct problems and oppositional sub-scores were significant predictors of increased serum zonulin levels. Conclusion: These data confirm an association between ADHD, and serum zonulin and occludin levels. Pathophysiological and clinical significance of these findings needs to be elucidated.

Potential relationship between Tourette syndrome and gut microbiome

Abstract Objective: In this article, the author aims to discuss and review the relationship between gut microbiota and Tourette syndrome, and whether the change in gut microbiota can affect the severity of Tourette syndrome. Sources: Literature from PubMed, Google Scholar, and China National Knowledge Infrastructure was mainly reviewed. Both original studies and review articles were discussed. The articles were required to be published as of May 2022. Summary of the findings: Current studies on the gut microbiome have found that the gut microbiome and brain seem to interact. It is named the brain-gut-axis. The relationship between the brain-gut axis and neurological and psychiatric disorders has been a topic of intense interest. Tourette syndrome is a chronic neurological disease that seriously affects the quality of life of children, and there appears to be an increase in Ruminococcaceae and Bacteroides in the gut of patients with Tourette syndrome. After clinical observation and animal experiments, there appear to be particular gut microbiota changes in Tourette syndrome. It provides a new possible idea for the treatment of Tourette syndrome. Probiotics and fecal microbial transplantation have been tried to treat Tourette syndrome, especially Tourette syndrome which is not sensitive to drugs, and some results have been achieved. Conclusions: The relationship between gut microbiota and Tourette syndrome and how to alleviate Tourette syndrome by improving gut microbiota are new topics, more in-depth and larger sample size research is still needed.

Brief review of pathophysiological disorders as consequence of psychological stress / Breve revisión de los trastornos fisiopatológicos como consecuencia del estrés psicológico

Background: Psychological stress is a reaction to an unexpected situation that favours adaptation and response to the event. However, when psychological stress is chronic or very intense, it can induce changes in various systems and tissues, causing diseases or aggravating existing ones. Objective: To briefly analyse the pathophysiological conditions caused by psychological stress. Method: A narrative review of the scientific literature on pathophysiological conditions as a consequence of psychological stress was performed. Results: Psychological stress can induce various conditions at the gastrointestinal, immune and cardiovascular levels. This is mainly due to the neurobiological and endocrine response because when faced with a stressful stimulus, a deregulated release of glucocorticoids and catecholamines is generated, altering the normal physiology of the organism. Gastrointestinal disorders are mainly due to goblet cell dysfunction, resulting in intestinal hyperpermeability, inflammation and infection. Changes at the immune level lead to an increase in inflammatory responses but a decrease in the protective activities of the immune system. Finally, cardiovascular conditions include atherosclerosis, increased blood pressure and stroke. Conclusion: Psychological stress can induce real physiological pathologies and, in some cases, fatal ones. Some of the molecular mechanisms involved in these pathologies have already been studied and identified. Knowledge of these molecular mechanisms can help clinicians and therapists to improve the treatment and therapy of patients.

Introducción: El estrés psicológico es una respuesta a una situación inesperada que favorece la adaptación y la respuesta ante dicho evento. Sin embargo, cuando el estrés psicológico es crónico o muy intenso, se pueden desencadenar afecciones en diversos sistemas y tejidos, generando enfermedades o empeorando las ya existentes. Objetivo: Analizar brevemente las afecciones fisiopatológicas causadas por el estrés psicológico. Método: Se realizó una revisión narrativa con la literatura científica sobre las afecciones fisiopatológicas debidas al estrés psicológico. Resultados: El estrés psicológico puede desencadenar diversas afecciones a nivel gastrointestinal, inmunitario y cardiovascular. Esto se debe principalmente a la respuesta neurobiológica y endócrina, ya que ante estímulos estresores, se genera una liberación desregulada de glucocorticoides y catecolaminas que alteran la fisiología normal del organismo. Las afecciones a nivel gastrointestinal se deben principalmente a la disfunción de las células caliciformes, dando como consecuencia hiperpermeabilidad intestinal, inflamación e infecciones. Las alteraciones a nivel inmunitario generan un aumento en las respuestas inflamatorias pero una reducción en las actividades protectoras del sistema inmune. Por último, las afecciones cardiovasculares incluyen ateroesclerosis, aumento de la presión arterial y derrames cerebrales, entre otros. Conclusión: El estrés psicológico puede causar patologías fisiológicas reales y, en algunos casos, mortales. Algunos de los mecanismos moleculares implicados en estas patologías ya han sido estudiados y establecidos. Conocer estos mecanismos moleculares puede ayudar a los médicos y terapeutas a mejorar el tratamiento y la terapia del paciente.