Retinal microcirculatory disorder is a key factor in the occurrence and development of diabetic retinopathy （DR）， and also an important link in the prevention and treatment of DR. The theory of "Gaozhuo" holds that the microcirculatory disorder in DR is based on the deficiency of spleen Qi and is characterized by the obstruction caused by "Gaozhuo" and blood stasis. The deficiency of spleen Qi is an essential precondition for the endogenous formation and accumulation of Gaozhuo， while Gaozhuo invasion is the direct cause of microcirculatory disorders in DR. The deficiency of spleen Qi and the endogenous formation of Gaozhuo mean the process in which glucose metabolism dysfunction induces an excessive production of inflammatory factors and lipid metabolites. The obstruction caused by "Gaozhuo" and blood stasis is the direct pathogenesis of microcirculatory disorders in DR， encompassing two stages： Gaozhuo obstruction and turbidity and stasis stagnation. Gaozhuo obstruction and turbidity and stasis stagnation represent the process in which inflammatory factors and lipid metabolites damage the retinal microcirculation and induce thrombosis， thus mediating microcirculatory disorders. Turbidity and stasis stagnation and blood extravasation outside the vessels reveal the progression to microvascular rupture and hemorrhage resulting from the microcirculatory disorders. According to the pathogenesis evolution of the theory of "Gaozhuo"， microcirculatory disorders in DR can be divided into deficiency of spleen Qi with Gaozhuo obstruction， deficiency of spleen Qi with turbidity and stasis stagnation， and turbidity and stasis stagnation with blood extravasation outside the vessels. Clinically， treatment principles should focus on strengthening the spleen and benefiting Qi， resolving turbidity， and dispersing stasis. Different syndrome patterns should be addressed with tailored therapies， such as enhancing the spleen and benefiting Qi while regulating Qi and reducing turbidity， strengthening the spleen and benefiting Qi while resolving turbidity and dispelling stasis， and strengthening the spleen and resolving turbidity while removing stasis and stopping bleeding. Representative prescriptions include modified Wendantang， modified Buyang Huanwutang， modified Danggui Buxuetang， Zhuixue Mingmu decoction， Tangmuqing， Shengqing Jiangzhuo Tongluo Mingmu prescription， Danhong Huayu decoction， and Yiqi Yangyin Huoxue Lishui formula.

Objective: To elucidate the potential mechanisms by which Chinese herbal medicine (CHM) regulates gut microbiota (GM) to influence the development of primary open-angle glaucoma (POAG). Methods: Data mining, network pharmacology, and Mendelian randomization (MR) analyses (two-sample design) were conducted in integration to systematically explore the CHM-GM-POAG axis. Literature-based data mining method was applied to identify frequently used herbs and herb pairs for POAG, and the properties and meridian tropism of the herbs were analyzed as well. Target prediction and pathway enrichment analyses were performed to identify shared molecular pathways among CHM components, GM, and POAG. MR analysis was performed to assess the genetically predicted causal associations between specific microbial taxa and POAG risk. Results: Our data mining work indicated that commonly used CHMs were mainly bitter and sweet in flavors and cold in property, with meridian tropism toward the liver, lung, and kidney. The predominant therapeutic effects of the CHMs included soothing the liver and regulating Qi, promoting blood circulation, and reducing fluid retention. Representative herb pairs were Shudihuang (Rehmanniae Radix Praeparata)-Gouqi (Lycii Fructus) with Zexie (Alismatis Rhizoma), Gouqi (Lycii Fructus)-Fuling (Poria) with Shudihuang (Rehmanniae Radix), and Juhua (Chrysanthemi Flos)-Gouqi (Lycii Fructus) with Zexie (Alismatis Rhizoma). Network pharmacology revealed overlapping targets involving antioxidative, anti-inflammatory, and metabolic regulation pathways. MR analysis demonstrated that higher abundances of Ruminiclostridium 6 [odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.58 – 0.92, P = 0.007], Ruminococcaceae UCG-002 (OR = 0.77, 95% CI: 0.63 – 0.96, P = 0.018), Ruminococcus torques group (OR = 0.71, 95% CI: 0.57 – 0.90, P = 0.004), and Victivallis (OR = 0.82, 95% CI: 0.70 – 0.96, P = 0.016) were causally associated with reduced POAG risk, whereas Actinomyces (OR = 1.34, 95% CI: 1.06 – 1.68, P = 0.013) and Blautia (OR = 1.39, 95% CI: 1.01 – 1.90, P = 0.042) showed positive associations. Conclusion This study revealed potential causal links between GM and POAG and provided integrative evidence that CHM may modulate the microbiota to exert neuroprotective effects. These findings offer new integrative insights into the gut-eye axis and a theoretical basis for developing microbiota-targeted CHM strategies in glaucoma management.

Objective:To investigate the value of multi-parameter MRI habitat imaging in differentiating human epidermal growth factor receptor 2 (HER2) expression in breast cancer.Methods:This study was cross-sectional. A retrospective analysis was conducted on the clinical and imaging data of 86 cases of primary invasive breast cancer confirmed by pathology at the Second Affiliated Hospital of Shantou University from August 2018 to July 2023. All patients were female, aged 33 to 74 (51±10) years. All patients underwent breast MRI examinations, including T 1WI, T 2WI, diffusion-weighted imaging and dynamic contrast-enhanced MRI. The fuzzy C-means clustering algorithm was applied to cluster analysis of the volume ratio of the extracellular extravascular space (V e), the rate constant (K ep), the volume transfer constant (K trans), and the apparent diffusion coefficient (ADC) for all lesions. Different habitat subregions were segmented based on breast cancer. Blood perfusion of the lesion was quantified through mean values of K trans and K ep, and cell proliferation was evaluated by the mean values of ADC and V e in each subregion. Additionally, the percentage of each subregion′s volume in relation to the total lesion volume was calculated. The Mann-Whitney U test was used to compare the differences in the volume percentages of various habitat subregions between different HER2 expression status. The diagnostic performance of statistically significant parameters in determining HER2 status was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:Among the 86 patients with invasive breast cancer, 27 were HER2 positive and 59 were HER2 negative. Among the HER2 negative patients, 37 had low and 22 had zero HER2 expression. The volume percentages of habitat subregions 1, 2, and 3 showed statistically significant differences between HER2 positive and HER2 negative patients ( Z=2.90, P=0.004; Z=-2.04, P=0.042; Z=-2.19, P=0.029), with AUC values of 0.696, 0.638, and 0.648, respectively, for predicting HER2 positive expression. The volume percentage of habitat subregion 2 showed a statistically significant difference between low and zero HER2 expression patients ( Z=2.85, P=0.004), with an AUC value of 0.724 for predicting low versus zero HER2 expression. Conclusions:The volume percentage of habitat subregion 1 effectively distinguishes HER2 status, and the volume percentage of habitat subregion 2 effectively distinguishes between low and zero HER2 expression patients. It has significant clinical implications for identifying potential candidates for HER2-targeted therapy.

Objective·To investigate the safety and feasibility of early goal-directed mobilization in the recovery of gastrointestinal function after pancreaticoduodenectomy.Methods·The non-contemporaneous controlled studies were conducted.Subjects who underwent pancreaticoduodenectomy were included.From Sep 2022 to May 2023,forty patients were selected as the control group,and forty patients were selected from June 2023 to February 2024 as the experimental group.The general clinical data of the two groups were collected.The control group was treated with the nursing routine after pancreaticoduodenectomy,and there were no specific requirements for the time and goal of early activity.The experimental group had daily activity goals established for early mobilization,which were performed by the patients and their families,while the rest of their care was identical to that of the control group.The main index of effectiveness evaluation was the time of first flatus and first defecation,and the secondary indexes included the time of first getting out of bed,the time of oral drinking,the time of the gastric tube removal,and the postoperative levels of K+,Na+,and Cl-on the 3rd day of the postoperative period.Safety evaluations included chyle leak,postoperative pancreatic fistula,biliary leak and delayed gastric emptying,postoperative hemorrhage,unplanned reoperation,unplanned extubation,falls and death.Results·There was no statistically significant difference in the general clinical data of the patients in the 2 groups.After the implementation of early goal-directed mobilization,the time of first flatus was advanced from(3.95±1.68)d to(2.88±0.91)d(t=-3.560,P=0.001),and the time of first defecation was advanced from(4.90±1.61)d to(3.80±1.30)d(t=-3.352,P=0.001).The time of first getting out of bed was advanced from(5.18±1.77)d to(2.30±0.88)d(t=-9.205,P＜0.001),and the time of oral drinking was advanced from(4.10±1.89)d to(2.73±1.20)d(t=-3.883,P＜0.001).Significant differences were also observed in postoperative day 3 Na+(t=-2.745,P=0.008)and Cl-(t=-2.033,P=0.045)levels.Conclusion·Early goal-directed activity programs are safe and effective in promoting the recovery of gastrointestinal function after pancreaticoduodenectomy.

Objective To explore the effects of electroacupuncture on motor function in Parkinson's disease(PD)model mice and NLRP3 inflammasome-related proteins in the midbrain substantia nigra(SN).Methods C57BL/6 mice were assigned to three groups according to the random number table method:control group,model group,and electroacupuncture(EA)group,12 mice per group.The PD model was reproduced by intragastric administration of rotenone solution 10 mg/(kg·d).EA group was administered at the three selected points,"Fengfu"(GV16),"Taichong"(LR3),and"Zusanli"(ST36),with a treatment cycle of 2 weeks.The control and model groups took the same time synchronous fixation operation for the control variable.Behavioral scores and open field tests were used to detect the exercise ability of mice in each group.Tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the midbrain SN of mice in all groups were measured with an immunohistochemistry test.NLRP3 and cysteinyl aspartate specific proteinase-1(Caspase-1)protein expression levels in the midbrain SN of mice in the three groups were measured using Western blotting,and interleukin-1β(IL-1β)content was determined with an enzyme-linked immunosorbent assay.Results Compared to the control group,the behavioral scores of the mice in the model group were higher(P<0.01).Compared to the model group,the behavioral scores of the mice in the EA group were lower(P<0.01).Compared to the control group,the time ratio of the relative rest state of the mice in the model group(<100 mm/s)increased significantly(P<0.01),while the time ratio of the slow motion(100～200 mm/s)and time ratio of the fast motion(>200 mm/s)state decreased significantly(P<0.01).Compared to the model group,the time ratio spent in the relative rest state of mice in the EA group decreased significantly(P<0.01),while the time ratio of the slow motion state and time ratio of the fast motion state and movement rate increased significantly(P<0.01).Compared to the control group,the TH expression level decreased in the SN in the model group(P<0.01),while α-syn increased(P<0.01).Compared to the model group,the TH expression level in the EA group increased(P<0.05),while α-syn decreased(P<0.05).Compared to the control group,the protein expressions of NLRP3 and Caspase-1 in the SN of the model group increased(P<0.01);compared to the model group,the expressions of NLRP3 and Caspase-1 in the SN of the midbrain of mice decreased after EA treatment(P<0.01).Compared to the control group,IL-1β in the SN of the mouse midbrain increased in the model group(P<0.01).Compared to the model group,IL-1β decreased in the EA group(P<0.05).Conclusion This experiment shows that stimulation of EA in"Fengfu","Taichong",and"Zusanli"can effectively reduce abnormal aggregation of the PD marker α-syn,increase TH expression,and enhance the motor dysfunction of PD model mice.The molecular mechanism is related to the regulation of the expression of NLRP3,Caspase-1,and IL-1β of inflammasome-related pathways.

Objective:To investigate the influences of Pinocembrin on inflammatory injury in rats with acute myocardial in-farction(AMI)by regulating TLR4/NF-κB/NLRP3 signaling pathway.Methods:The AMI model was established by coronary liga-tion,and the rats were grouped into Sham group,AMI group,Pinocembrin group(5 mg/kg tail vein injection),TLR4 inhibitor group(TAK-242 group,2.0 mg/kg tail vein injection),the levels of cardiac function indexes(LVEF,LVEDD,LVESD,FS)and serum LDH,cTnⅠ,IL-6,IL-β and TNF-α were detected in rats,TTC staining,HE staining and Masson staining were applied to observe myocardial infarction and myocardial histopathological changes in rats,cardiomyocyte apoptosis was detected by TUNEL method,im-munohistochemistry and Western blot were applied to detect TLR4/NF-κB/NLRP3 pathway-related proteins in rat myocardial tissue.Results:Compared with Sham group,the myocardial infarction area increased,the number of myocardial cells decreased,some myo-cardial fibers were broken,inflammatory cells infiltrated,collagen fibers increased,and the apoptosis rate was obviously increased in AMI group(P<0.05),LVEDD,LVESD,serum LDH,cTnⅠ,IL-6,IL-β,TNF-α levels,myocardial tissue TLR4,MyD88,p-NF-κB p65,NLRP3,Caspase-1 expression levels were obviously increased(P<0.05),while LVEF and FS were obviously decreased(P<0.05);compared with AMI group,the myocardial infarction area of the Pinocembrin group and the TAK-242 group were reduced,the cell damage and inflammatory infiltration were reduced,the necrotic cells were obviously reduced,and the apoptosis rate was obvious-ly reduced(P<0.05),LVEDD,LVESD,serum LDH,cTnⅠ,IL-6,IL-β,TNF-α levels,myocardial tissue TLR4,MyD88,p-NF-κB p65,NLRP3,Caspase-1 expression levels were decreased(P<0.05),LVEF and FS were obviously increased(P<0.05);there was no obvious difference in each index between Pinocembrin group and TAK-242 group(P>0.05).Conclusion:Pinocembrin may at-tenuate myocardial inflammatory injury caused by AMI by inhibiting TLR4/NF-κB/NLRP3 signaling pathway.

Objective To investigate whether the mechanism of action of electro-acupuncture in MPTP-induced Parkinson's disease(PD)model mice is related to neuroinflammation mediated by the forkhead box protein O1(FoXO1)/NOD-like receptor heat protein structural domain-related protein 3(NLRP3)signaling pathway.Methods Thirty mice were randomly divided into control(Ctrl),model(MPTP),and electro-acupuncture(EA)groups,with 10 mice in each group.PD mouse model was prepared by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)30 mg/(kg·d)for 7 d consecutively.Behavioral changes of mice were observed by open field and pole-climbing experiments;α-synuclein(α-syn)expression in the substantia nigra of the midbrain was observed by immunohistochemistry;FoXO1,NLRP3,ASC,and Caspase-1 were deter-mined by Western blot;and the expression of inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)was detected by ELISA in the substantia nigra of the midbrain.Results Mice in the MPTP group showed significant behavioral deficits,with a significant increase in midbrain substantia nigra α-syn(P＜0.01),elevated levels of Iba-1,FoXO1,NLRP3,ASC,and Caspase-1 proteins(P＜0.05 and P＜0.01,respectively),and a significant increase in the levels of TNF-α,and IL-1β(P＜0.01).The treatment of EA was effective in improve the dyskinesia of PD mice,improve motor balance and coordination(P＜0.01),reduce the abnormal aggregation of α-syn(P＜0.01),reduce the abnormal activation of microglia,and alleviate neuroinflammation(P＜0.05).Conclusion Electro-acupuncture may play a protective role in PD by modulating FoXO1/NLRP3 pathway-mediated neuroinflammation.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.