ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Endometriosis （EMT） is a common disease with frequent occurrence and difficult to be cured in modern clinical practice of obstetrics and gynaecology. It is characterized by progressively worsening dysmenorrhoea， pelvic mass， and infertility. The incidence of EMT is growing and increasingly younger patients are diagnosed with this disease， which poses a serious threat to the reproductive and psychological health of women of childbearing age and adolescent females. However， the pathogenesis of EMT is still not completely clear， and the disease has a long course. Therefore， developing new therapies is an urgent clinical problem to be solved. Great progress has been achieved in the treatment of EMT with traditional Chinese medicine （TCM）， while the underlying mechanism remains in exploration. Programmed cell death （PCD） is a cell death mode mediated by a variety of bio-molecules with specific signaling cascades. The known PCD processes include apoptosis， pyroptosis， autophagy， ferroptosis， and cuproptosis， which all play a pivotal role in the development of EMT. Researchers have made achievements in the treatment of EMT with TCM， which regulates PCD via multiple pathways， routes， targets， and mechanisms. However， the progress in the regulation of PCD in the treatment of EMT with TCM remains to be reviewed. This paper reviews the research progress in the treatment of EMT with TCM from five PCD processes （apoptosis， pyroptosis， autophagy， ferroptosis， and cuproptosis）， with the aim of providing a theoretical basis for the clinical prevention and treatment of EMT.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

ObjectiveTo investigate the effect of icariin （ICA） on the phenotype of dendritic cells （DCs） in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group， and male Dahl salt-sensitive rats were divided into a model group， low-， medium-， and high-dose ICA groups （30， 60， 120 mg·kg^-1·d^-1）， and Vitamin D group （3×10^-5 mg·kg^-1·d^-1）. In addition to the normal group， the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored， and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 （Th17）/regulatory T cell （Treg） ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor （VDR）， 1α-hydroxylase （CYP27B1）， 24-hydroxylase （CYP24A1）， forkhead frame protein 3 （FoxP3）， solitaire receptor γt （RORγt）， myocardial type Ⅰ collagen （ColⅠ）， and type collagen （ColⅢ） in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered arrangement and rupture of myocardial cells， nuclear condensation， significant edema of myocardial tissue， significant proliferation of collagen fibers in a network distribution， and a significant increase in tail artery blood pressure， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD） （P<0.05）. The phenotype of cardiac DCs was CD40， CD80， and CD86， and the levels of major histocompatibility complex Ⅱ （MHC-Ⅱ）， Th17 cells， and Th17/Treg were significantly increased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt in the heart， as well as the mRNA expression of ColⅠ and ColⅢ， were significantly increased （P<0.05）. The left ventricular ejection fraction （LVEF）， interventricular septal thickness （IVSD）， and left ventricular posterior wall thickness （LVPWD） were significantly decreased （P<0.05）. The phenotype of cardiac DCs such as CD11， CD11b， and Treg cells， were significantly reduced （P<0.05）， while the mRNA and protein expression of cardiac VDR， CYP27B1， and FoxP3 were significantly decreased （P<0.05）. Compared with the model group， the low-， medium-， and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation， improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure， LVEDD， and LVESD were significantly decreased in the low-， medium-， and high-dose ICA groups and vitamin D group （P<0.05）， and the phenotype of cardiac DCs including CD40， CD80， CD86， MHC-Ⅱ， Th17 cells， and Th17/Treg were significantly decreased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt， and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. The LVEF， IVSD， and LVPWD of myocardial remodeling model rats in the low-， medium-， and high-dose ICA groups and vitamin D group were significantly increased （P<0.05）. The phenotypes of cardiac DCs including CD11， CD11b， and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group （P<0.05）. The mRNA and protein expressions of VDR， CYP27B1， and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. ConclusionICA can regulate tail artery blood pressure， cardiac structural and functional damage， and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR， CYP24A1， and CYP27B1， achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue.

OBJECTIVE To investigate the effects of imperatorin （IMP-SD） on malignant biological behavior of gastric cancer （GC） cells by regulating zinc finger and BTB domain 7B （ThPOK）. METHODS Human GC cells MKN-7 were used as the research object and then divided into control group （no treatment）， IMP-SD low-， medium- and high-concentration groups （40， 80 and 160 μmol/L IMP-SD）， si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small interfering RNA （si-ThPOK） or its negative control （si-NC）]. After treatment， cell clone formation， migration and invasion abilities and apoptosis of MKN-7 cells were detected； the killing activity of NK cells， T cells classification， the protein expressions of ThPOK， programmed death-1 （PD-1） and programmed death-ligand 1 （PD-L1） were all determined. RESULTS Compared with the control group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， the ratio of CD4+ T proportion and CD8+ T proportion （CD4+ T/CD8+ T）， and the protein expression of ThPOK were increased or up-regulated significantly， in a concentration-dependent manner （P＜0.05）. Compared with IMP-SD high-concentration group and si-NC group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， CD4+ T/CD8+ T， and the protein expression of ThPOK were decreased or down-regulated significantly （P＜0.05）. CONCLUSIONS IMP-SD may reduce the clonal formation， migration and invasion abilities of GC cells， promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.

OBJECTIVE To investigate the effects of imperatorin （IMP-SD） on malignant biological behavior of gastric cancer （GC） cells by regulating zinc finger and BTB domain 7B （ThPOK）. METHODS Human GC cells MKN-7 were used as the research object and then divided into control group （no treatment）， IMP-SD low-， medium- and high-concentration groups （40， 80 and 160 μmol/L IMP-SD）， si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small interfering RNA （si-ThPOK） or its negative control （si-NC）]. After treatment， cell clone formation， migration and invasion abilities and apoptosis of MKN-7 cells were detected； the killing activity of NK cells， T cells classification， the protein expressions of ThPOK， programmed death-1 （PD-1） and programmed death-ligand 1 （PD-L1） were all determined. RESULTS Compared with the control group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， the ratio of CD4+ T proportion and CD8+ T proportion （CD4+ T/CD8+ T）， and the protein expression of ThPOK were increased or up-regulated significantly， in a concentration-dependent manner （P＜0.05）. Compared with IMP-SD high-concentration group and si-NC group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， CD4+ T/CD8+ T， and the protein expression of ThPOK were decreased or down-regulated significantly （P＜0.05）. CONCLUSIONS IMP-SD may reduce the clonal formation， migration and invasion abilities of GC cells， promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.

BACKGROUND:According to existing clinical studies,vertebroplasty treatment with both the external pedicle approach and the pedicle approach can improve the pain and quality of life of patients with spinal compression fractures.Compared with the pedicle approach,the external pedicle approach has a freer puncture angle,and good bone cement dispersion effect can be obtained by adjusting the puncture angle. OBJECTIVE:To compare the impact of vertebroplasty through individualized unilateral external pedicle approach and bilateral pedicle approach on the treatment of spinal compression fractures by quantifying the dispersion effect of bone cement. METHODS:A total of 80 patients with thoracolumbar compression fracture were divided into two groups by random number table method.The bilateral pedicle group(n=40)underwent vertebroplasty through a bilateral pedicle approach,while the unilateral external pedicle group(n=40)underwent individualized vertebroplasty through a unilateral external pedicle approach.Anteroposterior and lateral X-rays of the affected vertebrae from two groups of patients were photographed to assess effect and type of bone cement dispersion within 3 days after surgery.Visual analog scale score,tenderness threshold around fracture,and Oswestry dysfunction index were assessed before,1,7 days,and 1 month after surgery. RESULTS AND CONCLUSION:(1)Dispersion effect of bone cement in unilateral external pedicle group was better than that in bilateral pedicle group(P<0.001),and the amount of bone cement perfusion was higher than that in bilateral pedicle group(P<0.001).In the bilateral pedicle group,the bone cement dispersion types were mainly concentrated in type Ⅰ and type Ⅲ,while in the unilateral external pedicle group,the bone cement dispersion types were mainly concentrated in type I and type Ⅱ,and there was a significant difference in bone cement dispersion types between the two groups(P<0.001).(2)Postoperative visual analog scale scores and Oswestry disability index of both groups were lower than those before surgery(P<0.001),and postoperative tenderness threshold around fracture showed a trend of decreasing first and then increasing.At the same time point after treatment,there were no significant differences in visual analog scale score,Oswestry disability index,and tenderness threshold around fracture between the two groups(P>0.05).(3)The results indicate that individualized vertebroplasty via unilateral external pedicle approach can achieve better bone cement dispersion,and the treatment effect is consistent with the vertebroplasty via classical bilateral pedicle approach.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

BACKGROUND:Intertrochanteric fracture of femur has various fracture types and fixation methods,and the mechanical stability of each fixation system is quite different.It is of scientific clinical significance to use finite element analysis method to carry out biomechanical research on various fixation systems. OBJECTIVE:To compare and analyze the mechanical stability of various internal fixations applied to femoral intertrochanteric fracture A031-A2.1 by finite element method. METHODS:Based on the validated finite element model of femur(Intact),the model was cut and made into A031-A2.1 intertrochanteric fracture of femur.Different internal fixation systems were implanted by simulating clinical operation methods,and fixation models of proximal femoral nail antirotation,dynamic hip screw,percutaneous compression plate and proximal femoral locking plate were established respectively.All nodes under the distal femur of the four groups of models were constrained,and compression loads of 700,1 400 and 2 100 N were applied to the femoral head.Von Mises stress distribution and compression stiffness of each group of models were observed through calculation and analysis,and mechanical stability of each group was compared. RESULTS AND CONCLUSION:(1)Through calculation and analysis,after calculating the compression stiffness by comparing the deformation of each model,the compression stiffness of each model under various loads showed the trend:physiological group>proximal femoral nail antirotation group>proximal femoral locking plate group>percutaneous compression plate group>dynamic hip screw group.The compressive stiffness of the complete physiological group model was significantly higher than that of all surgical group models.(2)The stress index was observed.Due to the stress shielding effect,the stress peak value of each fixed group was higher than that of physiological group,and the maximum peak value was concentrated on each internal fixation.Proximal femoral nail antirotation group had the smallest stress peak,while dynamic hip screw group had the highest stress.The stress distribution trend showed physiological group