Retinopathy of prematurity (ROP) is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia. Here, we investigated the potential effects of alamandine, a novel heptapeptide in the renin-angiotensin system (RAS), on hypoxia-induced retinal neovascularization and its underlying mechanisms. In vivo, the C57BL/6J mice with oxygen-induced retinopathy (OIR) were injected intravitreally with alamandine (1.0 μmol/kg per eye). In vitro, human retinal microvascular endothelial cells (HRMECs) were utilized to investigate the effects of alamandine (10 μg/mL) on proliferation, apoptosis, migration, and tubular formation under vascular endothelial growth factor (VEGF) stimulation. Single-cell RNA sequencing (scRNA-seq) matrix data from the Gene Expression Omnibus (GEO) database and RAS-related genes from the Molecular Signatures Database (MSigDB) were sourced for subsequent analyses. By integrating scRNA-seq data across multiple species, we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group. Next, alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice. In vitro, alamandine effectively mitigated VEGF-induced proliferation, scratch wound healing, and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α (HIF-1α)/VEGF pathway. Further, coincubation with D-Pro⁷ (Mas-related G protein-coupled receptor D (MrgD) antagonist) hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro. Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway, providing a potential therapeutic agent for OIR prevention and treatment.
Animals ; Retinal Neovascularization/prevention & control* ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A/metabolism* ; Humans ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Oligopeptides/therapeutic use* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Endothelial Cells/drug effects* ; Retinopathy of Prematurity/drug therapy* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Renin-Angiotensin System/drug effects* ; Cells, Cultured

Traditional Chinese medicine(TCM)has rich experience in the diagnosis and treatment of epidemics,but the basic con-cepts and diagnosis and treatment strategies of TCM for epidemics have not yet formed a common understanding.This paper preliminar-ily constructs a diagnosis and treatment system of TCM epidemics from the perspective of"type differentiation-stage differentiation-syndrome differentiation"by combing the basic concepts of the etiology,pathogenesis,and identification of epidemics,taking state-target differentiation and treatment as the general principle.First,the epidemics are divided into five types:cold epidemics,warm epi-demics,cold-damp epidemics,damp epidemics,and miscellaneous epidemics;then,according to the overall course of the epidemics,they are divided into four stages:"initial stage-peak stage-extreme stage-relapse stage",the initial stage is the stage of exterior syn-dromes,the peak stage is the stage of heat peak,the extreme stage is the stage of internal closure and external loss,and the relapse stage is the stage of recovery of the healthy qi and retreat of the evil qi;finally,on the basis of staging,combined with the syndrome char-acteristics of various epidemics(five types of background diseases)at different stages,the syndromes are divided demonstratively.Through the construction of a modern diagnosis and treatment system of TCM epidemics,the basic theoretical concepts and basic diag-nosis and treatment strategies of epidemics can be clarified,various new and emerging infectious diseases can be actively responded to,and a diagnosis and treatment plan for a new and emerging infectious disease can be quickly constructed.

BACKGROUND:Chinese herbal prescription with head acupuncture exercise therapy has significant clinical efficacy in the treatment of limb spasticity after ischemic stroke;however,the exact mechanism is not clear.OBJECTIVE:To explore the possible mechanism of the combination of Chinese herbal prescription with head acupuncture exercise therapy in improving limb spasticity after stroke.METHODS:Seventy Sprague-Dawley rats were divided into blank,model,exercise therapy,head-acupuncture,Chinese herbal prescription,Chinese herbal prescription with head acupuncture exercise therapy,and sham-operation groups using the random number method,with 10 rats in each group.Except for the blank group and the sham-operation group,a rat model of cerebral ischemia/reperfusion injury was made by using the middle cerebral artery cable embolism method in the rest of the groups.Interventions in each group started on the 3rd day after modeling.In the Chinese herbal prescription group,rats were given 1.5 g/kg Yi'nao Fujian herbal prescription by gavage;in the head acupuncture group,acupuncture was applied to Baihui and 2 mm on the left and right sides of Baihui,and was left in place for 30 minutes;in the exercise therapy group,rats were exercised on a treadmill for 30 minutes;in the Chinese herbal prescription with head acupuncture exercise therapy group,1.5 g/kg Yi'nao Fujian herbal prescription was given by gavage followed by acupuncture treatment(identical to that in the head acupuncture group,and then the animals were exercised for 30 minutes on the treadmill while the acupuncture needles remained in place.Rats in the model and sham-operation groups were subjected to grasping under the same environmental conditions and placed on a rat immobilizer for 30 minutes,and the blank group did not have any intervention.The frequency of intervention in each group was once a day for 7 consecutive days.The neurological deficit score and muscle tone were evaluated in each group before and after treatment.Pathological changes in rat brain tissue were observed.Protein and mRNA expressions of glutamic acid decarboxylase 67,succinate semialdehyde dehydrogenase,and γ-aminobutyric acid transaminase in the cerebral cortex of the rats were detected.RESULTS AND CONCLUSION:(1)Compared with the model group,the Chinese herbal prescription with head acupuncture exercise therapy group had lower neurological deficit scores and modified Ashworth spasticity scale(MAS)muscle tone scores(P＜0.01),decreased expression of succinate semialdehyde dehydrogenase andγ-aminobutyric acid transaminase at protein and mRNA levels,and increased expression of expression of glutamic acid decarboxylase 67 at protein and mRNA levels(P＜0.01);the neuronal cell structure was relatively intact,with only some irregular cavities visible and reduced nuclear consolidation.(2)Compared with the Chinese herbal prescription with head acupuncture exercise therapy group,the neurological deficit scores and MAS muscle tone scores were higher in the exercise therapy group(P＜0.05),and the MAS muscle tone scores were higher in the head-acupuncture group and the Chinese herbal prescription group(P＜0.05,P＜0.01),while the expressions of glutamic acid decarboxylase 67 protein and succinate semialdehyde dehydrogenase andγ-aminobutyric acid transaminase mRNAs were increased in all the other intervention groups(P＜0.05,P＜0.01).Neuronal cells in the Chinese herbal prescription with head acupuncture exercise therapy group were more orderly arranged and clearly outlined,with less nuclear consolidation and shape irregularity compared with the other intervention groups.(3)The neurological deficit score and MAS muscle tone score in the Chinese herbal prescription with head acupuncture exercise therapy group were significantly lower after treatment(P＜0.01).To conclude,Yi'nao Fujian herbal prescription combined with head-acupuncture exercise therapy can improve post-stroke spasticity by affecting the expression of γ-aminobutyric acid transaminase in rats,which is more effective than Chinese herbal prescription alone,exercise therapy alone,and head-acupuncture alone.

Traditional Chinese medicine(TCM)has rich experience in the diagnosis and treatment of epidemics,but the basic con-cepts and diagnosis and treatment strategies of TCM for epidemics have not yet formed a common understanding.This paper preliminar-ily constructs a diagnosis and treatment system of TCM epidemics from the perspective of"type differentiation-stage differentiation-syndrome differentiation"by combing the basic concepts of the etiology,pathogenesis,and identification of epidemics,taking state-target differentiation and treatment as the general principle.First,the epidemics are divided into five types:cold epidemics,warm epi-demics,cold-damp epidemics,damp epidemics,and miscellaneous epidemics;then,according to the overall course of the epidemics,they are divided into four stages:"initial stage-peak stage-extreme stage-relapse stage",the initial stage is the stage of exterior syn-dromes,the peak stage is the stage of heat peak,the extreme stage is the stage of internal closure and external loss,and the relapse stage is the stage of recovery of the healthy qi and retreat of the evil qi;finally,on the basis of staging,combined with the syndrome char-acteristics of various epidemics(five types of background diseases)at different stages,the syndromes are divided demonstratively.Through the construction of a modern diagnosis and treatment system of TCM epidemics,the basic theoretical concepts and basic diag-nosis and treatment strategies of epidemics can be clarified,various new and emerging infectious diseases can be actively responded to,and a diagnosis and treatment plan for a new and emerging infectious disease can be quickly constructed.

BACKGROUND:Chinese herbal prescription with head acupuncture exercise therapy has significant clinical efficacy in the treatment of limb spasticity after ischemic stroke;however,the exact mechanism is not clear.OBJECTIVE:To explore the possible mechanism of the combination of Chinese herbal prescription with head acupuncture exercise therapy in improving limb spasticity after stroke.METHODS:Seventy Sprague-Dawley rats were divided into blank,model,exercise therapy,head-acupuncture,Chinese herbal prescription,Chinese herbal prescription with head acupuncture exercise therapy,and sham-operation groups using the random number method,with 10 rats in each group.Except for the blank group and the sham-operation group,a rat model of cerebral ischemia/reperfusion injury was made by using the middle cerebral artery cable embolism method in the rest of the groups.Interventions in each group started on the 3rd day after modeling.In the Chinese herbal prescription group,rats were given 1.5 g/kg Yi'nao Fujian herbal prescription by gavage;in the head acupuncture group,acupuncture was applied to Baihui and 2 mm on the left and right sides of Baihui,and was left in place for 30 minutes;in the exercise therapy group,rats were exercised on a treadmill for 30 minutes;in the Chinese herbal prescription with head acupuncture exercise therapy group,1.5 g/kg Yi'nao Fujian herbal prescription was given by gavage followed by acupuncture treatment(identical to that in the head acupuncture group,and then the animals were exercised for 30 minutes on the treadmill while the acupuncture needles remained in place.Rats in the model and sham-operation groups were subjected to grasping under the same environmental conditions and placed on a rat immobilizer for 30 minutes,and the blank group did not have any intervention.The frequency of intervention in each group was once a day for 7 consecutive days.The neurological deficit score and muscle tone were evaluated in each group before and after treatment.Pathological changes in rat brain tissue were observed.Protein and mRNA expressions of glutamic acid decarboxylase 67,succinate semialdehyde dehydrogenase,and γ-aminobutyric acid transaminase in the cerebral cortex of the rats were detected.RESULTS AND CONCLUSION:(1)Compared with the model group,the Chinese herbal prescription with head acupuncture exercise therapy group had lower neurological deficit scores and modified Ashworth spasticity scale(MAS)muscle tone scores(P＜0.01),decreased expression of succinate semialdehyde dehydrogenase andγ-aminobutyric acid transaminase at protein and mRNA levels,and increased expression of expression of glutamic acid decarboxylase 67 at protein and mRNA levels(P＜0.01);the neuronal cell structure was relatively intact,with only some irregular cavities visible and reduced nuclear consolidation.(2)Compared with the Chinese herbal prescription with head acupuncture exercise therapy group,the neurological deficit scores and MAS muscle tone scores were higher in the exercise therapy group(P＜0.05),and the MAS muscle tone scores were higher in the head-acupuncture group and the Chinese herbal prescription group(P＜0.05,P＜0.01),while the expressions of glutamic acid decarboxylase 67 protein and succinate semialdehyde dehydrogenase andγ-aminobutyric acid transaminase mRNAs were increased in all the other intervention groups(P＜0.05,P＜0.01).Neuronal cells in the Chinese herbal prescription with head acupuncture exercise therapy group were more orderly arranged and clearly outlined,with less nuclear consolidation and shape irregularity compared with the other intervention groups.(3)The neurological deficit score and MAS muscle tone score in the Chinese herbal prescription with head acupuncture exercise therapy group were significantly lower after treatment(P＜0.01).To conclude,Yi'nao Fujian herbal prescription combined with head-acupuncture exercise therapy can improve post-stroke spasticity by affecting the expression of γ-aminobutyric acid transaminase in rats,which is more effective than Chinese herbal prescription alone,exercise therapy alone,and head-acupuncture alone.

Objective:To investigate the levels of interleukin-7 (IL-7), T helper cell 9 (Th9), and cytotoxic T cell 9 (Tc9), and to assess the regulation of exogenous IL-7 to Th9 in septic cardiomypathy patients.Methods:A cross-sectional study was conducted. Septic cardiomypathy patients, septic patients, and controls were enrolled in the 7th People’s Hospital of Zhengzhou between June 2018 and January 2022. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. PBMCs were stimulated with recombinant IL-7. Plasma IL-7, IL-9, and soluble CD127 levels were measured by enzyme-linked immunosorbent assay. CD127 expression on T cells and Th9/Tc9 percentageswere measured by flow cytometry. mRNAexpressions of purine-rich nucleic acid binding protein 1 (PU.1) and forkhead box protein O1 (Foxo1) were semi-quantified by real-time PCR. IL-7-stimulated Th9 cells from septic cardiomypathy patients were co-cultured with autologous CD8 + T cells and human umbilical vein endothelial cells. Target cell death, cytotoxic molecules and cytokines secretions were investigated. Kruskal-Wallis test was used for comparison among groups, while Dunns multiple test was used for comparison between the two groups. Paired t test or Wilcoxon paired test was used for comparison before and after stimulation. Results:A total of 21 septic cardiomypathy patients, 56 septic patients, and 31 controls were enrolled. IL-7 level was lower in septic cardiomypathy patients compared with in septic patients and controls [75.71(42.28, 135.59) pg/mL vs. 118.47(60.18, 171.73) pg/mL vs. 168.42(105.41, 232.30) pg/mL, P<0.05]. Soluble CD127 level was higher in septic cardiomypathy patients and septic patients compared with in controls [96.70(56.76, 147.04) pg/mL vs. 69.75(43.19, 111.28) pg/mL vs. 29.13(19.33, 42.11) pg/mL, P<0.001]. There was no significant difference of CD127 +CD8 + percentage among three groups ( P=0.477). Th9 percentage and Foxo1 mRNA expression was lower in septic cardiomypathy patients compared with in septic patients and controls ( P<0.001). Tc9 percentage, PU.1 mRNA expression and IL-9 level was lower in septic cardiomypathy patients and septic patients compared with in controls ( P<0.001). Th9 percentage, PU.1/Foxo1 mRNA expression, and IL-9 secretion was up-regulated in response to IL-7 stimulation in PBMCs from septic cardiomypathy patients ( P<0.05). IL-7 stimulated Th9 cells from septic cardiomypathy patients promoted CD8 + T cell-mediated target cell death ( P<0.05). Perforin, granzyme B, and interferon-γ levels were also increased in the supernatants ( P<0.05). Conclusion:IL-7 could enhance Th9 cell activity in septic cardiomypathy patients.

BACKGROUND:Some patients still have unsatisfactory improvement of operative limb fatigue and pain after total knee arthroplasty.Clinical findings show that Jianpi Yiqi Huoxue Formula can promote recovery after total knee arthroplasty,but the specific efficacy remains to be studied. OBJECTIVE:To observe the effect of Jianpi Yiqi Huoxue Formula on the muscle strength and pain of the operated limb after the primary unilateral total knee arthroplasty. METHODS:A total of 74 patients undergoing primary unilateral total knee arthroplasty were randomly divided into a trial group and a control group with 37 patients in each group.All patients received the same prostheses and surgical methods during the operation.Patients in the control group were treated with routine analgesics,anticoagulant drugs and functional exercise after the operation.The trial group received Jianpi Yiqi Huoxue Formula after the treatment in the control group.Both groups were treated continuously and followed up for 1 month.The changes in isokinetic muscle strength(peak torque and total work amount of extensor and flexor),visual analog scale score and the hospital for special surgery score of the two groups were analyzed. RESULTS AND CONCLUSION:(1)The trial group had better improvement in peak torque and total work amount of extensor and flexor and the hospital for special surgery score than the control group 14 days and 1 month after surgery(P<0.05).(2)In contrast to the control group,the visual analog scale score of the trial group improved better at 7 and 14 days and 1 month after surgery(P<0.05).(3)It is indicated that Jianpi Yiqi Huoxue Formula can effectively improve the muscle strength of the operated limb,enhance the degree of postoperative joint pain,and promote functional rehabilitation after total knee arthroplasty.

The Menghe Medical School is a highly influential academic school of Chinese medicine in China.Its academic features are mainly learning from others'strengths,openness and tolerance;integrity as the foundation,communication as the strength;harmo-ny as the way,and agility as the technique.The Menghe Medical School originated in Menghe,developed in Shanghai,spread all over the country,and spread around the world.The reasons for the prosperity and development of the Menghe Medical School are analyzed.Among them,imperial doctors being rewarded and supported,the stars having their roots in Menghe,inheritance from teach-ers by blood,help from in-laws,and the establishment of education and leadership in development are the main factors.On the basis of inheriting the scholarship of Menghe Medical School,Professor Tong Xiaolin innovatively proposed academic ideas such as the train-ing path of Xiang thinking,state-target differentiation and treatment,and dosage and effectiveness of prescriptions and medicines,pushing the academic thought of Menghe Medical School to a new theoretical peak in the new era.Based on the majestic development path of the Menghe Medical School,the implications for the inheritance,innovation and development of modern Chinese medicine are analyzed.

Traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of Coronavirus disease 2019 (COVID-19) epidemic in China. The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment. According to a series of evidence-based studies, TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups. For patients with mild and moderate forms of COVID-19, TCM can relieve the related signs and symptoms, shorten the period of nucleic-acid negative conversion, and reduce conversion rate to the severe form of the disease. For COVID-19 patients with severe and critical illnesses, TCM can improve inflammatory indicators and blood oxygen saturation, shorten the hospital stay, and reduce the mortality rate. During recovery, TCM can improve patients' symptoms, promote organ function recovery, boost the quality of patients' life, and reduce the nucleic-acid repositive conversion rate. A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects, immune regulation, and protection of organ function via a multicomponent, multitarget, and multipathway approach.
Humans ; COVID-19 ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; SARS-CoV-2 ; Epidemics

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.