Protective effect of rhEPO on tight junctions of cerebral microvascular endothelial cells early following traumatic brain injury in rats.

OBJECTIVE: The goal of this study was to investigate the protective effect of recombinant human EPO(rhEPO) on cerebral microvascular endothelial cells and the mechanisms by which rhEPO interacts with TJs proteins, claudin-5, Occludin and ZO-1 during the early period following traumatic brain injury. RESEARCH DESIGN: Rats (n = 81) were randomly divided into sham-operated group, TBI group and rhEPO+TBI group. Traumatic brain injury was induced by the Marmarou method. METHODS AND PROCEDURES: Rats were killed at 3, 24, 72 and 168 hours after TBI. The integrity of the blood-brain barrier was investigated by using a spectrophotometer to assess extravasation of Evans blue dye. The expression of Claudin-5, Occludin and ZO-1 were determined by immunohistochemistry and real-time fluorescence quantitative PCR. RESULTS: From 3 hours to 3 days, rats in the TBI group demonstrated a remarkable increase in Evans blue content in the brain, relative to rats in the sham-operated group (p < 0.05). The expression of Claudin-5 and Occludin was significantly lower than those in the sham-operated group (p < 0.05). In contrast, rats in the TBI+rhEPO group demonstrated a significant decrease in brain levels. CONCLUSION: It was found that administration of rhEPO protected cerebral microvascular endothelial cells and reduced permeability of BBB and the mechanisms may be due to increasing the expression of TJs proteins.

Improving detection and notification of tuberculosis cases in students in Shaanxi province, China: an intervention study.

BACKGROUND: Cooperation between different public and private health institutes involved in tuberculosis (TB) control has proven to enhance TB control in different settings. In China, such a mechanism has not been set up yet between Centers for Disease Control (CDCs) and university hospitals despite an increased TB incidence among students. This study aims to improve arrival of TB suspects identified by universities at the CDCs in order to manage them under standardized, directly observed treatment-short course (DOTS) conditions according to the National Tuberculosis Programme (NTP) guidelines. METHODS: Five matched pairs of universities were randomly assigned to the control and intervention group. After a baseline survey, a cooperation mechanism between local CDCs and university hospitals was set up in the intervention group. The effects on referral of TB suspects to the local CDC, tracing by the local CDC, and arrival at the local CDCs were assessed. Differences were tested by means of the chi-square test. RESULTS: During the baseline survey, the referral, tracing and arrival rates were between 37% and 46%. After implementation of the cooperation mechanism, these rates had not changed in the control group but increased significantly in the intervention group: the referral, tracing and arrival rates were 97%, 95%, and 93%, respectively. CONCLUSIONS: It is feasible and effective to set up cooperation between CDCs and university hospitals to increase the number of TB suspects examined by CDCs and increase the number of TB patients treated under DOTS conditions. These public-public mix (PPM) activities should be expanded to cover all other university hospitals in China.

Spinal extradural meningeal cysts: an MRI evaluation of a case series and literature review.

STUDY DESIGN: Case series and literature review. OBJECTIVE: To analyze the characteristics of extradural spinal meningeal cysts (SMCs) by magnetic resonance imaging (MRI) and discuss their classifications and etiology, as well as exploring the choice of treatment. SUMMARY OF BACKGROUND DATA: Spinal extradural meningeal cysts are a rare type of SMC. They are also known as extradural/epidural spinal arachnoid cysts. According to Nabors' classification, they belong to the category of types I and II meningeal cysts. The etiology of spinal extradural cysts remains unclear. MATERIALS AND METHODS: We retrospectively analyzed the MRI scans of 18 cases of extradural arachnoid cyst, which were consecutively treated surgically at our institutions between June 1990 and November 2009. All cases were confirmed by surgery. Disonics 0.35T and Philips Gyroscan Intera 1.5T scanner with surface coils were used for patient scanning. MRI examination included routine sagittal T1-weighted/spin-echo , sagittal, and transverse T2-weighted scanning. The above scans were repeated after the administration of intravenous contrast 3 medium (gadolinium) in 12 patients. RESULTS: Seven of the 18 cases were located in the middle and lower thoracic spine, 3 in the lumbar spine, and 8 in the thoracolumbar junction. All cystic lesions were isointense compared with cerebrospinal fluid on the T1 and T2-weighted images. The lesions showed no enhancement after gadolinium administration. CONCLUSIONS: MRI had great sensitivity to and specificity for extradural arachnoid cysts and seemed to be the diagnostic procedure of choice before and after surgery. Accurate understanding of MRI features helps clinicians make preoperative diagnoses and guides the operation. The definitive treatment of SMCs involves total removal of the cyst and repair of the dural defect.

A functional magnetic resonance imaging study of human brain in pain-related areas induced by electrical stimulation with different intensities.

BACKGROUND: Pain-related studies have mainly been performed through traditional methods, which lack the rigorous analysis of anatomical locations. Functional magnetic resonance imaging (fMRI) is a noninvasive method detecting neural activity, and has the ability to precisely locate related activations in vivo. Moreover, few studies have used painful stimulation of changed intensity to investigate relevant functioning nuclei in the human brain. AIM: This study mainly focused on the pain-related activations induced by electrical stimulation with different intensities using fMRI. Furthermore, the electrophysiological characteristics of different pain-susceptible-neurons were analyzed to construct the pain modulatory network, which was corresponding to painful stimulus of changed intensity. MATERIALS AND METHODS: Twelve volunteers underwent functional scanning receiving different electrical stimulation. The data were collected and analyzed to generate the corresponding functional activation maps and response time curves related to pain. RESULTS: The common activations were mainly located in several specific regions, including the secondary somatosensory cortex (SII), insula, anterior cingulate cortex (ACC), thalamus, and other cerebral regions. Moreover, innocuous electrical stimulation primarily activated the lateral portions of SII and thalamus, as well as the posterior insula, anterior ACC, whereas noxious electrical stimulation primarily activated the medial portions of SII and thalamus, as well as the anterior insula, the posterior ACC, with larger extensions and greater intensities. CONCLUSION: Several specified cerebral regions displayed different response patterns during electrical stimulation by means of fMRI, which implied that the corresponding pain-susceptible-neurons might process specific aspects of pain. Elucidation of functions on pain-related regions will help to understand the delicate pain modulation of human brain.

Linear polarization difference imaging and its potential applications.

We demonstrate a novel linear polarization imaging technique and its potential application in dermatology. This technique records a series of images corresponding to different combinations of illumination and detection polarization and calculates intensity differences between orthogonal detection polarizations pixel by pixel. Fitting the polarization difference data to an analytical expression of the incident and detection polarization angles results in two new parameters, G and (phi3)/2. It is shown that G is strongly correlated to the order of alignment of the fibrous structure in the sample, and (phi3)/2 represents the angle of orientation of the fibers. Preliminary clinical testing implies that this method may be applied for medical diagnosis of skin diseases.

Beware of the "high functioning trap" - excessive status expectations in patients with bipolar depression / 四川精神卫生

Maintaining long-term stability of patient's condition is crucial in the treatment for bipolar disorder， while accurately assessing the patient's disease status is important and challenging in maintaining treatment. Excessive status expectation is common in patients with bipolar depression， which would warp the patient's perception of his or her own disease status and， thus， ultimately interfere with clinical decisions. Heightened vigilance should be given to such phenomenon. This paper explores the phenomenon and potential mechanisms of excessive status expectation in patients with bipolar disorder， providing ideas for related diagnosis， treatment and research. ［Funded by Jiangsu Provincial Science and Technology PProject （number， BE2015609）］

Microbial contamination status of swimming places for infants and young children in Shijia-zhuang City and comparison with other public places, 2021–2022 / 环境与职业医学

Background At present, China's Public places health management regulations list 7 categories and 28 sub-categories of public places, but infant and young child swimming places are not in the list yet. Objective To understand the microbial pollution status in commercial infant and young child swimming places in Shijiazhuang City, compare with the microbial pollution in other five types of public places, and find the potential safety hazards in infant and young child swimming places. Methods A total of 3438 microbial samples were collected from the environment of infant and young child swimming places and 5 types of public places (hotels, barber stores, waiting rooms, shopping malls and supermarkets, and conventional swimming places) in Shijiazhuang City from 2021 to 2022. Sampling and monitoring were carried out according to the requirements of Examination methods for public places—Part 6: Technical specifications of health monitoring (GB/T 18204.6-2013). Chi-square test was used to compare hygiene qualification by microbial indicators, and Kruskal-Wallis H test was used to compare overall distributions of total bacterial counts on the surface of public articles. Results From 2021 to 2022, the highest qualified rate of microbial indicators on the surface of public articles was Staphylococcus aureus (100%) for all tested public places in Shijiazhuang City, followed by coliforms (99.44%), and that of total bacterial count was relative low (92.83%). The qualified rate of total bacterial count on the surface of public articles in the swimming places for infants and young children was 87.76%, and the qualified rates in hotels, barber stores, waiting rooms, shopping malls and supermarkets were all above 92%, and the difference among the 5 types of places was statistically significant (P<0.001). The highest value of total bacterial count on the surface of public articles in the swimming places for infants and young children was 80000 CFU·(25 cm2)−1 [100 CFU·(25 cm2)−1=4 CFU·cm−2]; that in 4 types of public places such as hotels (except mouthwash cups), barber stores, waiting rooms, and shopping malls or supermarkets was 2500 CFU·(25 cm2)−1. The difference of total bacteria count on the surface of public articles was statistically significant in comparing infant and young child swimming places with hotels (except mouthwash cups) or barber stores (H=5.432, H=2.997, both Ps<0.05); but the difference was not significant in comparing with waiting rooms and shopping malls or supermarkets (P>0.05). The qualified rates of total bacteria count and coliforms in pool water of infant and young child swimming places were 45.99% and 74.69% respectively, and the two indicators in pool water of conventional swimming places were 94.57% and 98.91% respectively; both showed significant differences between the two types of public places (χ2=162.532, χ2=71.910, both Ps<0.001). Conclusion Compared to conventional swimming places, hotels, barber stores, waiting rooms, and shopping malls or supermarkets, the infant and young child swimming places are not optimistic in hygiene condition; therefore, there is an urgent need to formulate national health standards for infants and young child swimming places, and include them in standard management to further improve their hygiene condition.

Influence of quercetin on aging of bone marrow mesenchymal stem cells induced by microgravity / 中国药理学通报

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Clincal practice of pelvic exenteration for late complications of pelvic radiation injury / 中华胃肠外科杂志

Pelvic radiation injury can potentially involve multiple pelvic organs, and due to its progressive and irreversible nature, its late stage can be complicated by fistulas, perforations, obstructions and other complications involved multiple pelvic organs, which seriously affect the long-term survival and the quality of life of patients. As a multidisciplinary surgical approach, pelvic exenteration has potential application in the treatment of late complications of pelvic radiation injury by completely removing the irradiated lesion, relieving symptoms and avoiding recurrence of symptoms. In clinical practice, we should advocate the concept of "pelvic radiation injury", emphasize multidisciplinary collaboration, fully evaluate the overall status of patients, primary tumor and pelvic radiation injury. We should follow the principles of "damage-control" and "extended resection", and follow the principle of enhanced recovery after surgery to achieve the goal of ensuring the surgical safety, relieving patients' symptoms and improving patients' quality of life and long-term survival.

Research progress of selective small molecule bromodomain-containing protein 9 inhibitors.

The bromodomain proteins, known as the key targets in epigenetics, are 'readers' of acetylated lysine of histones. As a member of bromodomain proteins, bromodomain-containing protein 9 (BRD9) is a subunit of mammalian SWI/SNF chromatin remodeling complexes. However, the biological functions and the potential application in therapeutics of BRD9 remain ambiguous due to a lack of selective small molecule inhibitors of BRD9. Recently, series of chemical ligands against BRD9 were developed by different research institutes. Here, we reviewed the development and characterization of reported BRD9 inhibitors, which will be the foundation of further chemical design and biological evaluation.

The injury of major organs and expression of inflammatory cytokines in mice with early infection of Vibrio vulnificus through respiratory tract / 解放军医学杂志

Objective Establishing animal model of Vibrio vulnificus(V.vulnificus)early infection via respiratory tract,to observe the survival,pathological changes of target organs and the expression changes of inflammatory cytokines in model mice,and to provide references for the relevant prevention and treatment strategies.Methods A total of 24 healthy female BALB/c mice(8 to 10 weeks old)were randomly divided into 4 groups(6 mice per group),including control group and three infection groups(low,medium and high concentration of infection,respectively),based on which the V.vulnificus infection models were established by intranasal administration.The survival statistics,status of defecation,hair and respiration as well as mental state of mice were monitored during 0-12 h early infection progress.Hematoxylin-eosin(HE)staining was performed on the important organs of mice to analyze the pathological manifestations,and immunohistochemical staining was used to detect the expression of interleukin(IL)-6,IL-10,interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α)in the target organs.Mouse inflammation panel combined with flow cytometry was used to further detect the changes of multiple inflammatory and anti-inflammatory cytokines in serum.Results V.vulnificus infection via respiratory tract caused mice deterioration in survival rate,defecation,hair status,respiratory tract and mental state within 12 h.HE pathological analysis showed inflammatory cell infiltration and cell necrosis in ileum,lung,liver and spleen of mice in different infection groups,and the injury was much severer in high concentration of infection group.Immunohistochemical results reflected the positive expression rates of IL-6,IL-10,IFN-γ and TNF-α in ileum,lung,liver and spleen of mice in medium and high concentration of infection groups were significantly higher than those in control group(P<0.05).The results of mouse inflammation panel and flow cytometry showed that compared with the control group,the expression levels of TNF-α and monocyte chemotactic protein(MCP)-1 in all three infection groups were significantly increased(P<0.05),and the expression level of IL-27 significantly decreased(P<0.05);the expression levels of IL-1β,IL-6,IL-17A and granulocyte-macrophage colony-stimulating factor(GM-CSF)were significantly increased in medium and high concentration of infection groups(P<0.05);the expression levels of IL-1α,IL-23,IL-12p70 and IFN-γ were significantly increased in high concentration of infection group(P<0.05).Conclusions V.vulnificus infection progressed rapidly through respiratory tract in mice,and lung,intestine,liver and spleen were major target organs.Accompanied by increased secretion of multiple serum inflammatory cytokines,V.vulnificus infection through respiratory tract might further causes severe inflammatory reaction in hosts.

Synergistic effect of Hsp90 inhibitor ginkgolic acids C15 ꞉1 combined with paclitaxel on nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms.@*METHODS@#This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting.@*RESULTS@#Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax).@*CONCLUSIONS@#The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.

[Relation between ICOS signaling and Th9 cell polarization in mice infected with Schistosoma japonicum].

OBJECTIVE: To detect the expression level of ICOS on Th9 cells in mice infected with Schistosoma japonicum, and investigate the relation between ICOS signaling and Th9 cell polarization. METHODS: Twenty-five mice with S. japonicum infection were used as models. IL-9+cells in CD4+ T cells and ICOS+ cells in Th9 cells of the mice were detected by flow cytometry 0, 4, 7, 9 weeks and 12 weeks after the infection. RESULTS: Compared with that 0 week after the infection, the proportion of Th9 cells in CD4+ T cells of the mice significantly increased 4, 7, 9, 12 weeks after the infection (all P < 0.05), and the proportion of ICOS+ cells in Th9 cells also markedly improved (P < 0.05). CONCLUSIONS: In S. japonicum infection, the ICOS signaling may have a regulatory effect on Th9 cell polarization.

The role and treatment progress of ferroptosis in osteoarthritis / 中国医师杂志

Osteoarthritis is a chronic inflammatory disease characterized by non inflammatory degeneration of articular cartilage and the formation of osteophytes at the edge of the joint, caused by complex causes. Its pathology is complex, and its pathogenesis is not yet clear, ultimately leading to joint stiffness and functional activity disorders. At present, the treatment for osteoarthritis is limited to alleviating symptoms and improving function, with varying degrees of side effects. Ferroptosis is a new type of programmed cell death discovered in recent years, which is related to the pathological and physiological processes of osteoarthritis and plays an important regulatory role in the occurrence and development of osteoarthritis. Its main characteristics include iron metabolism imbalance and accumulation of reactive oxygen species. Therefore, ferroptosis inhibitors targeting ferroptosis have shown great application prospects in the treatment of osteoarthritis. In this review, the author summarizes the relevant mechanisms of ferroptosis in the occurrence and development of osteoarthritis, outlines a large number of specific therapeutic drugs and their corresponding targets, with the aim of delaying and reversing the progression of osteoarthritis by regulating chondrocyte ferroptosis, which has certain clinical guiding significance.

Research progress in drugs targeting 5-lipoxygenase for age-related diseases / 生理学报

With the acceleration of aging society, delaying aging or promoting healthy aging has become a major demand for human health. 5-Lipoxygenase (5-LOX) is a key enzyme catalyzing arachidonic acid into leukotrienes (LTs), which is a potent mediator of the inflammatory response. Previous studies showed that abnormal activation of 5-LOX and overproduction of LTs are closely related to the occurrence and development of aging-related inflammatory diseases. Therefore, inhibiting 5-LOX activation is a possibly potential strategy for treating age-related diseases. In this paper, the latest research progress in 5-LOX activation, 5-LOX in mediating aging-related diseases and its small molecule inhibitors is briefly reviewed to provide scientific theoretical basis and new ideas for the prevention and treatment of aging-related inflammatory diseases.

Effects of RNA M6A demethylase ALKBH5 gene deficiency on morphology and function of cerebellum in aged mice / 中华病理学杂志

Objective: To investigate the effects of RNA m6A demethylase ALKBH5 gene deficiency on cerebellar morphology and function in the aged mice, and to explore the role of ALKBH5 in cerebellar degeneration. Methods: Western blot was performed to detect the protein level of ALKBH5 in the cerebellum of wild-type mice of various ages. The expression of NeuN, Calbindin-D28K, MAP2, GFAP and other proteins in the cerebella of middle-aged (12-month-old) and aged (18-month-old) wild-type mice and ALKBH5-/- mice was examined using immunohistochemistry. The balance beam test and gait analysis were performed to test the balance ability and motor coordination of the mice. Results: With aging of the mice, the expression of ALKBH5 in the cerebellum increased gradually in an age-dependent manner. In the aged mice, but not middle-aged mice, the body weight, whole brain weight and cerebellum weight of ALKBH5-/- mice decreased by 15%, 10% and 21%, respectively (P<0.05). The expression of ALKBH5 in the Purkinje cells was much higher than that in other types of neural cells. Correspondingly, ALKBH5-deficiency caused 40% reduction in the number of Purkinje cells, as well as the length and density of neuronal dendrites in the aged mice (P<0.01). In addition, the time for the aged ALKBH5-/- mice to pass the balance beam was 70% longer than that of the wild type mice of the same age, with unstable gaits (P<0.01). Conclusions: Gene deficiency of RNA m6A demethylase ALKBH5 causes cerebellar atrophy, Purkinje neuron loss and damage in the aged mice. These changes eventually affect mice's motor coordination and balance ability. These results suggest that imbalanced RNA m6A methylation may lead to neurodegenerative lesions in the cerebellum of mice.

Modification of C20 oxidase in tanshinone biosynthesis pathway / 中国中药杂志

Tanshinones are one of the main effective components of Salvia miltiorrhiza, which play important roles in the treatment of cardiovascular diseases. Microbial heterogony production of tanshinones can provide a large number of raw materials for the production of traditional Chinese medicine(TCM) preparations containing S. miltiorrhiza, reduce the extraction cost, and relieve the pressure of clinical medication. The biosynthetic pathway of tanshinones contains multiple P450 enzymes, and the catalytic element with high efficiency is the basis of microbial production of tanshinones. In this study, the protein modification of CYP76AK1, a key P450-C20 hydroxylase in tanshinone pathway, was researched. The protein modeling methods SWISS-MODEL, Robetta, and AlphaFold2 were used, and the protein model was analyzed to obtain the reliable protein structure. The semi-rational design of mutant protein was carried out by molecular docking and homologous alignment. The key amino acid sites affecting the oxidation activity of CYP76AK1 were identified by molecular docking. The function of the obtained mutations was studied with yeast expression system, and the CYP76AK1 mutations with continuous oxidation function to 11-hydroxysugiol were obtained. Four key amino acid sites that affected the oxidation acti-vity were analyzed, and the reliability of three protein modeling methods was analyzed according to the mutation results. The effective protein modification sites of CYP76AK1 were reported for the first time in this study, which provides a catalytic element for different oxidation activities at C20 site for the study of the synthetic biology of tanshinones and lays a foundation for the analysis of the conti-nuous oxidation mechanism of P450-C20 modification.

Short-term exposure to gossypol causes reversible reproductive toxicity and nephrotoxicity in mice / 南方医科大学学报

OBJECTIVE@#To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible.@*METHODS@#Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity.@*RESULTS@#Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity.@*CONCLUSIONS@#Shortterm treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.

Quality evaluation of Cnidii Fructus in commodity grade based on theory of "quality evaluation through morphological identification" / 中国中药杂志

From the perspective of market classification of Cnidii Fructus, this paper revealed the scientific connotation of evaluating the quality grade of Cnidii Fructus by its appearance traits. Thirty batches of Cnidii Fructus in different grades were selected as the research objects. The canonical correlation analysis and principal component analysis(PCA) were used to explore the measurement values of 15 appearance traits and intrinsic content indexes. The results of correlation analysis showed that except the aspect ratio, the 5 appearance trait indexes(length, width, 1 000-grain weight, broken grain weight proportion, and chroma) and 9 internal content indexes(the content of moisture, total ash, acid insoluble ash, osthole, imperatorin, 5-methoxy psoralen, isopimpinellin, xanthotoxin, and xanthotol) showed significant correlation to varying degrees. In addition, there was a significant positive correlation between the first typical variable U_1 composed of appearance traits and the first typical variable V_1 composed of internal content indexes(CR_1=0.963, P<0.01). The results of PCA showed that the classification results of appearance traits for 30 batches of Cnidii Fructus were consistent with the actual information of the samples. Under the same analysis conditions, 30 batches of Cnidii Fructus were reclassified by 9 groups of internal content indexes, and the analysis results were consistent. From the classification standard of the appearance traits of the system study, the statistical results of 6 appearance traits of Cnidii Fructus showed a correlation with grades. There was a good correlation between the appearance and the internal content of Cnidii Fructus, and the appearance quality effectively predicted the level of the internal content. There is a certain scientific basis for the quality classification of Cnidii Fructus by main appearance traits. Appearance classification can replace quality grading to realize the "quality evaluation through morphological identification" of Cnidii Fructus.

Exploring the key anti-fatigue components of American ginseng based on metabolomics and zebrafish models / 药学学报

The aim of this paper is to explore the key anti-fatigue active components in the saponin-like composition of American ginseng. The anti-fatigue activity of western ginseng samples was evaluated using a zebrafish model; metabolomics techniques were used to identify the main saponins in western ginseng from different origins; the active substances and relevant targets of the anti-fatigue effect of western ginseng were initially screened by constructing a PPI protein interaction network between western ginseng saponins and disease targets, and the key active ingredients were screened using a molecular docking method; finally, the anti-fatigue activity of the key active ingredients was evaluated using a zebrafish, animal experiment was approved by the Ethics Committee of Shandong Academy of Medical Sciences (SYXK20220005). The anti-fatigue activity of the key active ingredients was evaluated using a zebrafish model. The results of the zebrafish activity evaluation showed that there were significant differences in the activities of the western ginseng samples from the two origins, and a total of 10 different saponins were identified as possibly related to the anti-fatigue activity after further metabolomic testing and pattern discrimination. The core anti-fatigue targets were screened with the help of component-disease target PPI, combined with pharmacophore-like parameters and molecular docking techniques, and pseudoginsenoside F11 was found to have good binding activity to five of the targets. Finally, the zebrafish model revealed that pseudoginsenoside F11 exhibited significant anti-fatigue activity. This study used metabolomics and zebrafish model to screen the key active substances of pseudoginsenoside F11 for its anti-fatigue activity, which will provide a reference for further research on the anti-fatigue of pseudoginsenosides.