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

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

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.

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.

Objective To explore imaging characteristics of myxofibrosarcoma(MFS)and their correlations with prognosis.Methods Totally 32 patients with pathologically confirmed MFS were retrospectively enrolled and divided into poor prognosis(recurrence/metastasis)group(n=13)and good prognosis group(n=19).Preoperative imaging characteristics of lesions were analyzed and compared between groups,including the location,shape,size,margins,density/signal features of lesions,adjacent bone destruction,peritumoral edema,fascial tail sign,enhancement patterns and tumor vasculature.Results MFS predominantly involved the extremities,especially the lower limbs,and the lesions commonly appeared as iso-to hypodensity masses with internal isodensity fibrous septations on non-enhanced CT.On non-enhanced MRI,MFS commonly demonstrated iso-to hypointense signals on T1WI,markedly hyperintense signals on T2WI,low signal fibrous septa,high signals on diffusion weighted imaging(DWI),as well as tail signs and surrounding soft tissue edema.After administration of contrast agents,solid components of MFS demonstrated marked enhancement.No statistical difference of tumor vascularity was detected between groups(P=0.141,1-β=0.269).Poor prognosis group showed significantly higher rates of diffuse peritumoral edema and fascial tail signs than good prognosis group(both P＜0.05).Conclusion Imaging features of MFS had certain characteristics,and the tail sign and surrounding soft tissue edema were correlated with poor prognosis.

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

Objective To explore imaging characteristics of myxofibrosarcoma(MFS)and their correlations with prognosis.Methods Totally 32 patients with pathologically confirmed MFS were retrospectively enrolled and divided into poor prognosis(recurrence/metastasis)group(n=13)and good prognosis group(n=19).Preoperative imaging characteristics of lesions were analyzed and compared between groups,including the location,shape,size,margins,density/signal features of lesions,adjacent bone destruction,peritumoral edema,fascial tail sign,enhancement patterns and tumor vasculature.Results MFS predominantly involved the extremities,especially the lower limbs,and the lesions commonly appeared as iso-to hypodensity masses with internal isodensity fibrous septations on non-enhanced CT.On non-enhanced MRI,MFS commonly demonstrated iso-to hypointense signals on T1WI,markedly hyperintense signals on T2WI,low signal fibrous septa,high signals on diffusion weighted imaging(DWI),as well as tail signs and surrounding soft tissue edema.After administration of contrast agents,solid components of MFS demonstrated marked enhancement.No statistical difference of tumor vascularity was detected between groups(P=0.141,1-β=0.269).Poor prognosis group showed significantly higher rates of diffuse peritumoral edema and fascial tail signs than good prognosis group(both P＜0.05).Conclusion Imaging features of MFS had certain characteristics,and the tail sign and surrounding soft tissue edema were correlated with poor prognosis.

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.

This article highlighted the invaluable expertise of Academician TONG Xiaolin in managing severe cases of COVID-19， thereby providing ideas for the treatment of severe and critically ill patients with SARS-CoV-2 infection by integrating traditional Chinese and western medicine. It is believed that COVID-19 belongs to the “cold dampness epidemic” in traditional Chinese medicine， which is caused by pathogenic qi of cold and dampness. The course of the disease can be divided into four stages： constraint， block， collapse， and deficiency， and the severe cases are mainly in the block and collapse stages. The pathogenesis at the block stage is described as epidemic toxins blocking the lung， which should be treated by diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals. The primary formula used is Zilong Xuanbai Chengqi Decoction （子龙宣白承气汤） with modifications based on individual condition. The pathogenesis at the collapse stage is described as internal block and external collapse， which should be treated by restoring yang to save from collapse， boosting qi to relieve collapse， diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals， usually with the formula Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications.

Epidemic cerebrospinal meningitis shows a high degree of consistency with the law of transmission among wei （卫）-qi-ying （营）-blood， in terms of the onset of the season， contagiousness， symptoms， pathogenesis， as well as characteristics of the transmission. It is proposed to use epidemic cerebrospinal meningitis as an example to explore the underlying disease of wei-qi-ying-blood syndrome differentiation system. Epidemic meningitis invades the brain from the upper respiratory tract along the nervous system， and its overall pathogenesis follows from entering the lung system （prodromal period） to entering the blood （bacteremia period， sepsis period） and then entering the brain （shock period）. According to the four-dimensional qualitative principle of epidemic pathogen tropism， it corresponds to disease of both wei and qi syndrome， then blazing of both qi and ying syndrome， and then heat blocking pericardium， exuberant heat stirring wind， and internal block and external collapse syndrome. This article explored the laws of transmission among wei-qi-ying-blood and its underlying diseases described in On Warm Heat （《温热论》）， and revealed the original appearance of the disease model under the laws of transmission among wei-qi-ying-blood to guide the clinical practice.