The concept of holism is the core idea of traditional Chinese medicine （TCM）. Various organs and tissues coordinate with each other to maintain the body's life activities， with a close and mutual influence between the spleen， stomach， and the central nervous system （brain）. The gut-brain axis plays an important bridging role between the digestive system and the central nervous system， achieving bidirectional information exchange between the brain and the gastrointestinal tract through complex neuroendocrine and immune mechanisms. The theory of cross-organ interaction involves the mutual influence， coordination， and integration between different organs and systems； multimodality， on the other hand， utilizes multiple sensory modalities， such as vision， hearing， and touch， to convey information. By combining TCM theory with the gut-brain axis theory， a cross-organ multimodal characterization system is established to explore its mechanism and application value in refractory diseases such as functional gastrointestinal disorders， precancerous gastrointestinal diseases， Alzheimer's disease， Parkinson's syndrome， type 2 diabetes， and depression.

Immune checkpoint inhibitors （ICIs） have shown good efficacy in tumor treatment and have changed the landscape of tumor treatment. However， some patients treated with ICIs have not only failed to achieve the desired therapeutic effect， but also developed an atypical response pattern of abnormally accelerated tumor growth， namely hyperprogressive disease （HPD）. The pathogenesis of HPD is still unclear and it is difficult to diagnose， which poses a challenge for clinical identification and treatment decisions. Exploring the underlying mechanism of HPD is important to improve the effect of immunotherapy. Based on the theory of "Yang deficiency and toxic knot"， this paper discussed the mechanism of HPD in immunotherapy from the perspective of "spleen and kidney Yang deficiency and hefty toxic pathogens". It was concluded that the inactivation of p53 oncogene and immunosuppressive microenvironment were the manifestations of the deficiency of healthy qi in the body and declined yang in the spleen and kidney， serving as an important basis for the occurrence of HPD. Adverse reactions caused by ICIs belong to the category of "drug toxicity". The occurrence and development of murine double minute 2 （MDM2）/murine double minute 4 （MDM4） activation， epidermal growth factor receptor （EGFR） mutation， and tumor inflammatory microenvironment are the manifestations of the hyperactivity of pathogenic Qi， conflict of cancer toxicity and drug toxicity， and being hefty by virtue of deficiency， which can promote the abnormal proliferation of tumor cells， and they are the core pathogenic elements of HPD and are closely related to disease prognosis. In terms of treatment， under the guidance of the theory of "five views on differentiation and treatment" （time-space view， core view， symptom view， precision view， and disease-before-onset view）， which was summarized according to the clinical practice of this research team， this paper， taking the prevention and treatment of HPD as the entry point， formulated traditional Chinese medicine （TCM） compounds to reinforce healthy Qi and warm Yang and realize the dynamic management of the whole spatiotemporal cycle， and removed toxins and resisted cancer to realize the all-round systemic intervention of the specimen. Additionally， targets were enriched in the macro-clinical manifestations and microscopic pathological changes of HPD to improve the targeting of drug selection and the precision of prevention and treatment， giving full play to the unique therapeutic advantages of TCM， and providing new ideas for the clinical application of TCM in the prevention and treatment of HPD.

Objective:To explore the therapeutic effect and psychological influence of biofeedback pelvic floor muscle training on fecal incontinence after anorectal surgery in children.Methods:A retrospective case-control study.A total of 37 children who were admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to April 2023 for fecal incontinence after anorectal surgery were collected.Biofeedback pelvic floor muscle training was performed with a Laborie biofeedback therapy device, and pelvic floor muscle contraction function exercise was performed no less than 200 times a day.The anal canal current intensity, basic motion myoelectric value, contractile myoelectric difference and continuous anal contraction time were measured at before treatment, at the end of 1 course, 1 month and 1 year after treatment.Ten healthy children of the same age were selected as the healthy control group.The Strengths and Difficulties Questionnaire was used for psychological evaluation at before treatment and 1 year after treatment.Paired sample t test and independent sample t test were used to compare and analyze the results of this study. Results:Before treatment, at the end of 1 course, 1 month and 1 year after treatment, the anal canal current intensity of children with fecal incontinence were(11.32±1.92) mA, (10.22±1.28) mA, (8.45±1.09) mA, and(7.80±1.23) mA, respectively; the anal canal basic motion myoelectric value were(235.58±55.03) μV, (185.65±34.30) μV, (124.81±36.56) μV, and(93.99±28.29) μV, respectively; the anal canal contractile myoelectric difference were(45.64±20.38) μV, (64.20±16.59) μV, (93.63±25.53) μV, and(109.83±26.95) μV, respectively; the continuous anal contraction time were(1.27±0.43) s, (1.58±0.40) s, (2.04±0.39) s, and(2.47±0.38) s, respectively.These parameters before treatment, at the end of 1 course and 1 month after treatment were significantly different from those in the healthy control group[(7.20±1.09) mA, (88.65±21.76) μV, (120.73±27.57) μV, (2.68±0.29) s](all P<0.05).These parameters at 1 year after treatment were significantly different from those before treatment and 1 month after treatment(all P<0.05).However, there were no significant differences in these parameters between the healthy control group and the treatment group at 1 year after treatment(all P>0.05).There were statistically significant differences in emotional symptoms, hyperactivity symptoms, peer interaction, prosocial behavior and difficulty scores before and after treatment[(3.46±1.88) points vs.(2.59±1.32) points, (5.78±2.12) points vs.(3.70±1.78) points, (3.05±1.72) points vs.(2.49±1.30) points, (7.30±1.54) points vs.(8.27±1.39) points, (21.57±4.57) points vs.(18.54±3.14) points](all P<0.05). Conclusions:Biofeedback pelvic floor muscle training is a reliable and non-invasive method for the treatment of postoperative fecal incontinence after anorectal surgery in children and can effectively relieve the psychological and behavioral problems caused by fecal incontinence in children.

Astrocytes are important nerve cells in the central nervous system （CNS）， which mainly play a key role in nutrition and support. Astrocytes and neurons undergo close energy coupling and substance coupling， which are closely related and interact with each other. In recent years， many studies have shown that the astrocyte-neuron coupling imbalance plays a central role in the occurrence and progression of Alzheimer's disease （AD） and serves as an important therapeutic target receiving increasing attention. According to traditional Chinese medicine （TCM） theory， the main pathogenesis of AD is kidney deficiency and marrow inadequacy， and in clinical medication， kidney-tonifying and marrow-filling TCM prescriptions are often employed with satisfactory results achieved. As reported， many kidney-tonifying and marrow-filling prescriptions exhibit regulatory and protective effects on the imbalance of astrocyte-neuron coupling， suggesting that the effect of kidney-tonifying and marrow-filling prescriptions in treating AD may have some internal relationship with its regulation of the imbalance of astrocyte-neuron coupling. This article reviewed the underlying internal relationship between the imbalance of astrocyte-neuron coupling and the pathogenesis of kidney deficiency and marrow inadequacy in AD and the research progress in the intervention mechanism of TCM for tonifying the kidney and filling the marrow.

ObjectiveTo explore the mechanism of Dihuang Yinzi in improving astrocyte injury and glycolysis in Alzheimer's disease （AD） mice via regulating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， thereby improving the cognitive function of AD mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. The mice in the control + Dihuang Yinzi group and the model + Dihuang Yinzi group were administered with Dihuang Yinzi by gavage， and those in the control group and the model group received an equal volume of sterilized normal saline， once a day for 150 days. Morris water maze test was performed to test the ability of navigation and space exploration of mice. The protein expression of p-PI3K， PI3K， p-Akt， Akt， phosphofructokinase-1 （PFK-1）， and aldehyde dehydrogenase 3 family member B2 （ALDH3B2） in mouse brain tissues was measured by Western blot. An immunofluorescence assay was performed to detect astrocyte morphology and the expression level of ALDH3B2. ResultAs compared with the control group， the model group showed prolonged escape latency during the 2^nd to 5^th days of the location-based navigation （P<0.05， P<0.01）， reduced number of times crossing the target area of the platform， shortened residence time in the target quadrant （P<0.05， P<0.01）， prolonged residence time in the opposite quadrant （P<0.05）， increased surface area of the cell body and total length of cell protrusions of astrocytes （P<0.05， P<0.01）， and down-regulated protein expression of p-PI3K， p-Akt， ALDH3B2， and PFK-1 （P<0.01）， while the above experimental indexes were not significantly different in the control + Dihuang Yinzi group. Compared with the model group， the model + Dihuang Yinzi group showed shortened escape latency of APP/PS1 mice during the 2^nd to 5^th days of the location-based navigation （P<0.05， P<0.01）， increased number of times crossing the platform， prolonged target quadrant residence time （P<0.05， P<0.01）， shortened residence time in the opposite quadrant （P<0.05）， reduced surface area of the cell body and total length of cell protrusions of astrocytes （P<0.05）， and up-regulated protein expression of p-PI3K， p-Akt， ALDH3B2， and PFK-1 （P<0.01）. ConclusionDihuang Yinzi can improve the learning and memory ability of AD mice by activating the PI3K/Akt signaling pathway and up-regulating the protein expression of PFK-1 and ALDH3B2 to protect against astrocyte injury in brain tissues and improve glycolysis.

ObjectiveTo explore the mechanism of Dihuang Yinzi （DHYZ）in improving astrocyte injury in the brain and regulating energy metabolism and autophagy disorder in Alzheimer's disease （AD） model mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + DHYZ group （2.5 g·kg^-1）， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + DHYZ group （2.5 g·kg^-1）， with 20 mice in each group. The mice in the control group and the model group were administered with an equal volume of sterilized normal saline by gavage， once a day for 150 days. Novel object recognition test and step-down test were performed to evaluate the learning and memory ability of mice. The expression of glial fibrillary acidic protein （GFAP） in astrocytes was detected by immunofluorescence and Western blot. High-performance liquid chromatography （HPLC） was used to detect adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in brain tissues of mice， and the data obtained were used to calculate energy charge （EC） levels. The phosphorylation levels of liver kinase B1 （LKB1）， adenosine 5′-monophosphate （AMP）-activated protein kinase （AMPK）， UNC-51-like kinase 1 （ULK1）， and mammalian target of rapamycin （mTOR） and the expression levels of autophagy-related proteins Beclin-1， microtuble-associated protein 1 light chain 3 （LC3）-Ⅱ/LC3-Ⅰ， and p62 in mouse brain were measured by Western blot. ResultCompared with the control group， the model group showed decreased novel object recognition index， shortened retention latency， increased error times in the step-down test， up-regulated protein expression of GFAP， decreased content of ATP， ADP， and EC in brain tissues， elevated AMP ， increased levels of p-AMPK， p-LKB1， and p-mTOR， and protein expression of p62 ， and down-regulated p-ULK1 level and protein expression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰ（P<0.01）， while the above experimental indexes were not significantly different in the control + DHYZ group. Compared with the model group， the model + DHYZ group showed increased novel object recognition index（P<0.05）， prolonged retention latency（P<0.01）， decreased error times（P<0.01） in the step-down test， reduced protein expression of GFAP（P<0.05）， increased content of ATP， ADP， and EC in brain tissues （P<0.05， P<0.01）， decreased AMP content（P<0.05）， reduced p-AMPK， p-LKB1， and p-mTOR levels and protein expression of p62， and up-regulated p-ULK1 level and protein expression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰ（P<0.01）. ConclusionBy protecting astrocytes， DHYZ can improve energy metabolism and autophagy disorder in AD mice to improve the learning and memory ability of model mice.

ObjectiveTo investigate the mechanism of Dihuang Yinzi in improving astrocyte injury and protecting synaptic structure and function in the brain of Alzheimer's disease （AD） mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. The mice in the control + Dihuang Yinzi group and the model + Dihuang Yinzi group were administered with Dihuang Yinzi by gavage， and those in the control group and the model group received an equal volume of sterilized normal saline， once a day for 150 days. The learning and memory ability of mice was tested by the light-dark box test and Y-maze spontaneous alternation test. The content of glutamate （Glu） and glutamine （Gln） was measured by liquid chromatography-tandem mass spectrometry （LC-MS）. Long-term potentiation （LTP） assay was used to detect synaptic plasticity in brain tissues. The protein expression levels of excitatory amino acid transporter 2 （EAAT2）， postsynaptic density protein95 （PSD95）， and synaptophysin （SYN） in brain tissues were measured by Western blot. Immunofluorescence was used to assess the localization and expression of EAAT2. Colorimetry was performed to detect Na⁺-K⁺ ATPase activity in mouse brain tissues. ResultAs compared with the control group， the model group showed shortened residence latency （P<0.01）， increased number of errors （P<0.01） in the light-dark box test， reduced spontaneous alternation behaviors （P<0.01）， no significant difference in the total number of arm entries in the Y-maze spontaneous alternation test， down-regulated expression of EAAT2， PSD95， and SYN （P<0.01）， blunted activity of Na⁺-K⁺ ATPase （P<0.01）， up-regulated Glu level （P<0.01）， down-regulated Gln level （P<0.01）， and reduced relative population spike （PS） amplitude and the slope of excitatory postsynaptic potential （EPSP） （P<0.05， P<0.01）， while the above experimental indexes were not significantly different in the control + Dihuang Yinzi group. Compared with the model group， the model + Dihuang Yinzi group displayed prolonged residence latency （P<0.05）， decreased number of errors （P<0.01） in the light-dark box test， increased spontaneous alternation behaviors （P<0.01）， no significant difference in the total number of arm entries in the Y-maze spontaneous alternation test， up-regulated expression of EAAT2， PSD95， and SYN （P<0.01）， potentiated activity of Na⁺-K⁺ ATPase （P<0.01）， reduced Glu level （P<0.01）， up-regulated Gln level （P<0.01）， and increased PS amplitude and EPSP slope （P<0.01）. ConclusionDihuang Yinzi can improve cognitive dysfunction in AD mice by protecting astrocytes， increasing Glu uptake to reduce its abnormal accumulation， and protecting synaptic structure and function.

Background The human body is usually exposed to a variety of heavy metals at the same time, and different types and concentrations of heavy metals may have complex interactions during their absorption and metabolism in the human body. Seminal fructose is an important energy source for sperm movement. A large number of studies have shown that metal exposure may impair semen quality, and seminal fructose is an important factor affecting male reproduction, so it is necessary to investigate the relationship between mixed heavy metal exposure and seminal fructose to explore the mechanism of semen quality damage caused by metal exposure. Objective To understand the status of common heavy metal exposure in men of childbearing age in Puyang City, Henan Province, and to study the relationship between mixed exposure to heavy metals and seminal fructose, as well as potential interactions among heavy metals. Methods Volunteers were recruited from the Puyang Maternal and Child Health Hospital Reproductive Center for a cross-sectional survey on general demographic characteristics, smoking, alcohol consumption, and other information. Semen samples were collected to detect 12 metals such as vanadium (V), manganese (Mn), cobalt (Co), nickel (Ni), zinc (Zn), selenium (Se), silver (Ag), cadmium (Cd), barium (Ba), thallium (Tl), iron (Fe), and lead (Pb) in seminal plasma and seminal fructose. After correcting for selected confounding factors, a Bayesian kernel machine regression (BKMR) model was used to evaluate the impact of seminal plasma heavy metal mixed exposure and its interactions on seminal fructose. Results A total of 825 adult males were enrolled. The concentrations in M (P₂₅, P₇₅) of V, Mn, Co, Ni, Zn, Se, Ag, Cd, Ba, Tl, Fe, and Pb in seminal plasma were 0.39 (0.28, 0.54), 12.31 (8.92, 17.52), 0.26 (0.18, 0.38), 5.15 (3.32, 8.64), 182159.80 (121847.80, 199144.50), 13.61 (10.55, 17.68), 0.03 (0.02, 0.04), 0.34 (0.27, 0.46), 8.64 (5.94, 13.43), 0.06 (0.05, 0.08), 168.74 (114.17, 259.45), and 1.69 (1.15, 2.36) μg·L⁻¹ respectively. The Spearman correlation results indicated that there was a negative correlation between V, Mn, Co, Zn, Se, Ba, Tl, or Fe in seminal plasma and seminal fructose (P<0.05), and the values of r (95%CI) were −0.044 (−0.087, −0.001), −0.129 (−0.171, −0.087), −0.055 (−0.099, −0.012), −0.099 (−0.143, −0.056), −0.053 (−0.097, −0.010), −0.068 (−0.111, −0.025), −0.095 (−0.138, −0.052), and −0.082 (−0.125, −0.039), respectively. The results of multiple linear regression indicated that there was a negative correlation between the exposure level of Cd, Mn, Zn, Ag, Ba, Tl, or Fe in seminal plasma and seminal fructose (P<0.05), the values of associated β (95%CI) were −0.551 (−0.956, −0.147), −0.315 (−0.419, −0.212), −0.187 (−0.272, −0.103), −0.161 (−0.301, −0.021), −0.188 (−0.314, −0.062), −1.159 (−2.170, −0.147), and −0.153 (−0.230, −0.076), respectively. The BKMR model analysis showed that seminal fructose level decreased with the increase of plasma metal mixed exposure concentration. Compared with all metal exposure at P₅₀, the seminal fructose level decreased by 0.2374 units when all metal exposure was at P₇₅. Seminal plasma Zn [posterior inclusion probabilities (PIPs)=1.0000] had the strongest effect on seminal fructose, followed by Mn (PIPs=0.5872), Se (PIPs=0.5656), and Ba (PIPs=0.5398). The univariate exposure-response curve showed a negative approximate linear correlations between Ba or Mn and seminal fructose, a positive linear correlation between Se and seminal fructose, and an approximate inverted U-shaped association between Zn and seminal fructose. No significant interaction between studied metals was found. Conclusion Mixed metal exposure may lead to decrease of seminal fructose, in which Zn, Mn, Se, and Ba may play an important role. Mn and Zn exposure may reduce the level of seminal fructose, Se may increase the level of seminal fructose, and there may be a threshold effect between Zn exposure and seminal fructose level. No interaction between different metals on seminal fructose is found.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

Objective:To investigate the value of the 8-channel eye surface phased array coil in improving image quality and demonstrating ocular masses on 3.0 T MR scanner.Methods:From July 2018 to January 2020, the data of orbital MRI in 692 patients with ocular masses on 6 medical centers were prospectively collected. The patients were simple randomly assigned into 8-channel eye surface phased array coil group (413 patients) or 8-channel head phased array coil group (279 patients), with the same MRI sequences. The signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated in orbital anatomy structures and masses (eyelid mass, intraocular mass, lacrimal mass and orbital mass). The image quality scores including motion artifact, mass margin, the relationship between the mass and adjacent structures, and overall image quality were recorded. The differences of image quality between the two groups were compared by two independent sample t-test or Wilcoxon rank test. Results:The SNR and CNR were higher in eye surface coil group than those in head coil group ( P<0.05). The scores of ocular movement artifacts were higher in head coil group than those in surface coil group ( P<0.05). The scores of intraocular mass margin, the relationship between the mass and adjacent structures, and overall image quality were higher in surface coil group than those in head coil group ( P<0.001). There were no significant differences in mass margin, the relationship between the mass and adjacent structures, and overall image quality scores of eyelid, lacrimal gland, and orbital mass between the two groups ( P>0.05). Conclusion:3.0 T MR scanner combined with the 8-channel eye surface phased array coil can improve the SNR and CNR of orbital MR images, the demonstration of the intraocular mass margin and the relationship between the mass and adjacent structures.