Based on the theory of "disease of both blood and water" in Essentials from the Golden Cabinet （《金匮要略》）， and in combination with the dynamic syndrome evolution of heart failure with preserved ejection fraction （HFpEF）， this paper systematically clarifies the pathomechanism of HFpEF， characterized by yang deficiency as the root， blood stasis as the pivotal factor and water retention as the manifestation. Accordingly， the therapeutic principles have been proposed， which are warming yang and banking up original qi to consolidate the root， activating blood and unblocking collaterals to smooth the mechanism， and promoting urination and regulating pivot to remove the branch. On this basis， a compound formula structure of "one monarch， one minister and one assistant" is established， forming an integrated intervention strategy that synergistically combines the three methods of warming yang， activating blood， and promoting urination through combined classical formulas. Zhenwu Decoction （真武汤）， which warms yang and dissolves rheum， is used to consolidate the root and directly target the source of yang deficiency， serving as the monarch； Guizhi Fuling Pills （桂枝茯苓丸）， which activates blood， promotes urination and unblocks the pivot， assists in interrupting the binding of blood stasis and water retention， serving as the minister； Tingli Dazao Xiefei Decoction （葶苈大枣泻肺汤）， which regulates qi， disperses retained fluids， and eliminates the manifestation， alleviates acute water-retention symptoms， serving as the assistant. This compound formula is warming without being drying， diuretic without being drastic， and dispels stasis without consuming blood， thereby achieving the therapeutic effects of warming yang， activating blood， and promoting urination.

The rupture of carotid vulnerable plaques is the core pathological basis for major cardiovascular and cerebrovascular events. However， the insufficient alignment between existing animal models and the clinical disease and syndrome characteristics of traditional Chinese and western medicine has limited research progress. In this study， biomedical databases in China and abroad were systematically searched， and the modeling mechanisms and evaluation systems of carotid vulnerable plaque animal models were systematically assessed based on diagnostic criteria of both traditional Chinese and western medicine. Analysis of the clinical correspondence indicated that existing animal models can be categorized into four types： simple high-fat diet， surgical induction combined with high-fat feeding， genetic engineering combined with high-fat feeding， and drug induction combined with high-fat feeding. Among these， the compound strategy of surgical induction combined with high-fat feeding has become the current mainstream approach， showing good concordance with western medicine. The study found that the double balloon injury rabbit model and the ApoE^-/- mouse carotid artery tandem constriction combined with high-fat feeding model demonstrated a high degree of clinical correspondence with both traditional Chinese and western medicine in terms of vulnerable plaque imaging and pathological features. Nevertheless， existing models still face significant technical limitations in faithfully simulating plaque pathology and in translating findings to clinical applications. To address these challenges， integrating complex comorbidity mechanism construction， multimodal dynamic mechanism monitoring， and collaborative evaluation systems of traditional Chinese and western medicine could enable the development of highly concordant carotid vulnerable plaque disease-syndrome combination animal models. Such models would provide a reproducible experimental platform for targeted drug development to regulate plaque stability and for individualized precision treatment， as well as a theoretical basis for innovation in clinical diagnostic and therapeutic strategies.

Repeated transcranial magnetic stimulation (rTMS) is one of the commonly used brain stimulation techniques. In order to investigate the effects of rTMS on the excitability of different types of neurons, this study is conducted to investigate the effects of rTMS on the cognitive function of mice and the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons from the perspective of electrophysiology. In this study, mice were randomly divided into glutaminergic control group, glutaminergic magnetic stimulation group, gamma-aminobutyric acid energy control group, and gamma-aminobutyric acid magnetic stimulation group. The four groups of mice were injected with adeno-associated virus to label two types of neurons and were implanted optical fiber. The stimulation groups received 14 days of stimulation and the control groups received 14 days of pseudo-stimulation. The fluorescence intensity of calcium ions in mice was recorded by optical fiber system. Behavioral experiments were conducted to explore the changes of cognitive function in mice. The patch-clamp system was used to detect the changes of neuronal action potential characteristics. The results showed that rTMS significantly improved the cognitive function of mice, increased the amplitude of calcium fluorescence of glutamergic neurons and gamma-aminobutyric neurons in the hippocampus, and enhanced the action potential related indexes of glutamergic neurons and gamma-aminobutyric neurons. The results suggest that rTMS can improve the cognitive ability of mice by enhancing the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons.
Animals ; Mice ; Hippocampus/cytology* ; Transcranial Magnetic Stimulation ; Neurons/physiology* ; Male ; Cognition/physiology* ; gamma-Aminobutyric Acid/metabolism* ; Action Potentials/physiology*

Objective:To conduct bioinformatics analysis by detecting and screening differentially expressed miRNAs in urine exosomes of subjects with damp heat IgA nephropathy, non damp heat IgA nephropathy, and healthy individuals; To explore the role of miRNAs in renal tubulointerstitial fibrosis.Methods:A cross-sectional study was conducted to select 40 subjects with primary IgA nephropathy diagnosed by renal biopsy in the Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University from November 2021 to February 2023, who were divided into damp-heat group and non-damp-heat group according to TCM constitution, with 20 cases in each group; 10 healthy subjects were also recruited for control observation.High-speed centrifugation and Illumina high-throughput sequencing technology were used to isolate and detect the expression of miRNA in urine exosomes from three groups of people, and their differential expression profiles were constructed. Bioinformatics analysis was performed on differentially expressed genes to determine the main biological functions of differentially expressed miRNAs and the signaling pathways they may participate in.Results:Compared with the non-damp heat group, there were 231 miRNAs with abnormal expression in the urine exosomes of the damp heat group, including 119 up-regulated and 112 down-regulated. Through GO enrichment and KEGG analysis, differentially expressed miRNAs may participate in the occurrence and development of renal tubulointerstitial fibrosis through MAPK signaling pathway, PI3K Akt signaling pathway, Hippo signaling pathway, Ras signaling pathway, Wnt signaling pathway, mTOR signaling pathway, etc., involving biological processes such as cell proliferation, apoptosis, cell deformation (EMT), migration and invasion, and tissue and organ fibrosis. MiR-29c-3p expression levels in the urinary exosome miRNA expression profiles of subjects in the three groups were lower in the damp-heat group, but higher in the non-damp-heat group versus the healthy control group, of which, the damp-heat group was lower than the non-damp-heat group versus the healthy control group ( P<0.01); there was no significant difference between the healthy control group and the non-damp-heat group ( P>0.05）. Conclusion:The expression profile of miRNAs in the urine exosomes of subjects with damp heat IgA nephropathy showed significant changes,that the significant down-regulation of miR-29c-3p may be a key factor in exacerbating tubulointerstitial fibrosis in IgA nephropathy.

Acceptance commitment therapy is accepted as a new psychological therapy to provide psychological treatment and rehabilitation for soldiers,to ensure their health level and maintain the combat effectiveness of the army.In this paper,the applications of acceptance commitment therapy in military personnel are reviewed,including improving post-traumatic stress disorders,relieving postoperative or chronic pain,mitigating anxiety and depression,controlling weight,quitting smoking,and controlling alcohol use disorders.Acceptance commitment therapy is highly applicable among soldiers,especially veterans,exceedingly effective among female soldiers with post-traumatic stress disorders and better than other traditional therapies in treating post-traumatic stress disorders combined with substance use disorders or combined with chronic pain.However,traditional therapy is more effective than acceptance commitment therapy in improving sleep.Unfortunately,the number of current studies is small,research is not widely-distributed geographically,and domestic studies are lacking.Multi-center randomized controlled studies with large samples on the basis of foreign studies are needed to verify the applicability of acceptance commitment therapy in Chinese military.

Objective: To construct a Family with sequence similarity 50 member A(FAM50A) gene knockout mouse insulinoma pancreatic β-cell line Beta-TC-6 using CRISPR/Cas9 gene editing technology and to prepare polyclonal antibodies specifically recognizing FAM50A. Methods: Two guide RNAs(sgRNAs) targeting the FAM50A gene were designed,and a recombinant plasmid expressing blue fluorescent protein(BFP) was constructed for gene knockout.The successfully constructed plasmid was transfected into Beta-TC-6 cells,and BFP-positive single cells were isolated for clonal expansion.The expanded monoclonal cell lines were genotyped by Sanger sequencing,and FAM50A protein expression was assessed by Western blot.Purified human recombinant FAM50A protein was used to immunize New Zealand rabbits for the preparation of a polyclonal antibody.The specificity of the prepared antibody was then validated using the successfully established FAM50A knockout cell line. Results: A monoclonal cell line with a successful knockout of the FAM50A gene was identified.Sanger sequencing confirmed base deletions at the target site.Western blot analysis showed a complete absence of FAM50A protein expression in this cell line.The prepared polyclonal antibody successfully recognized endogenous murine FAM50A protein in wild-type Beta-TC-6 cells and in hTERT-RPE1 cells overexpressing human FAM50A-GFP fusion protein,while no signal was detected in the FAM50A knockout cells. Conclusion This study successfully established a FAM50A gene knockout Beta-TC-6 cell model and generated a FAM50A polyclonal antibody,providing powerful tools for future research.

AIM:To observe the anti-scarring effects and safety of triamcinolone acetonide(TA)-loaded hydrogel sustained-release sheeting on stab incision glaucoma surgery(SIGS)with “one-step tunnel method” in rabbit eyes.METHODS:A total of 48 healthy New Zealand white rabbits were randomly selected and divided into 4 groups(12 rabbits in each group), trabeculectomy(Trab)group, SIGS group, polyvinyl alcohol hydrogel(PVAH)sheeting was implanted under the conjunctiva flap during SIGS(PVAH group), and hydrogel sustained-release sheeting loaded with TA was implanted under the conjunctiva flap during SIGS(TA/PVAH group). On the 1, 2, 3, and 4 wk after surgery, the intraocular pressure, filtering bubble morphology, anterior chamber reaction, and other complications were observed and recorded in each group. Then animals were euthanized, and the surgery area tissues of right eye were taken for pathological tissue paraffin section. Masson staining, picric acid-Sirius rose red staining, as well as α-smooth muscle actin(α-SMA)and fibroblast growth factor 2(FGF2)immunohistochemistry staining was performed on every section. The infiltration of inflammatory cells, proliferation of fibroblasts and synthesis of type I and type III collagen fibers in local tissues were observed. The average positive area ratio of α-SMA and FGF2 antibody immunohistochemical staining in each group was calculated and compared.RESULTS: The TA/PVAH group maintained diffuse and elevated functional filtering blebs, while flat filtering blebs appeared in Trab, SIGS and PVAH groups at 2 wk after surgery. Functional filtering blebs were present in 1 eye(33%), 2 eyes(67%)in the PVAH and TA/PVAH group at 4 wk after surgery, respectively, while the other filtering blebs were flattened. Masson staining showed that the hydrogels in PVAH and TA/PVAH groups did not degrade at 4 wk after surgery. Compared with the Trab and SIGS groups, the filtration passages were more obvious, with less collagen fiber proliferation. Sirius red staining showed that the expression of type I collagen and type III collagen in the TA/PVAH group was less than that in the Trab group, SIGS group and PVAH group at 4 wk after surgery. Immunohistochemical staining showed that the α-SMA expression in the TA/PVAH group was significantly lower than that in the Trab and SIGS groups at 1 wk after surgery(P<0.01). The α-SMA expression was the highest in the Trab and SIGS groups at 2 wk after surgery, while the α-SMA expression in the PHAP and TA/PVAH groups was significantly lower than that in the first two groups(P<0.01). Compared with the Trab group, the expression of FGF2 in the PVAH and TA/PVAH group was significantly increased at 1, 2, 3 and 4 wk after surgery(P<0.05). Compared with the SIGS group, FGF2 expression in the TA/PVAH group was significantly increased at 4 wk after surgery(P<0.05).CONCLUSION:In SIGS surgery of rabbit eyes, implanting hydrogel sustained-release sheeting loaded with TA under conjunctival flap can effectively inhibit the scarring of the filtering bleb, which may be the interaction of the anti-scar effect of TA and the stent function of hydrogel.

Objective To investigate the expression level and clinical application value of serum resistin in patients with systemic lu-pus erythematosus(SLE).Methods Forty-five SLE patients visited Nanjing Drum Tower Hospital,Clinical College of Nanjing Uni-versity of Chinese Medicine from January to August 2023 were enrolled in the study.The patients were scored and grouped according to the SLE disease activity index(SLEDAI),with SLEDAI＜9 score in the inactive group(n=32)and SLEDAI≥9 score in the active group(n=13).Thirty-four healthy individuals who underwent physical examination in our hospital were recruited as healthy controls.The clinical data and laboratory related indicators such as urine protein and serum complement C3 levels were collected from SLE pa-tients and healthy controls.Serum resistin levels were detected by enzyme-linked immunosorbent assay(ELISA).The clinical screening value of serum resistin for SLE was evaluated with the receiver operating characteristic(ROC)curve.The correlations of serum resistin levels with different laboratory indicators were determined by Pearson correlation analysis.Results The serum resistin levels in SLE patients([7.64±0.64]ng/mL)were significantly higher than that in healthy controls([2.56±0.43]ng/mL),and the difference was statistically significant(t=6.195,P＜0.01).The serum resistin levels in active SLE patients([10.10±1.45]ng/mL)were significant-ly higher than that in inactive SLE patients([6.64±0.60]ng/mL),and the difference was statistically significant(t=2.632,P＜0.05).The area under the ROC curve(AUCROC)of serum resistin for screening SLE was 0.897.When the cut-off value was 5.893 ng/mL,the sensitivity was 86.67%and the specificity was 82.35%.The serum resistin level in SLE patients was positively correlated with urine protein(r=0.692,P＜0.01),while negatively correlated with serum complement C3(r=-0.354,P＜0.05).Conclusion The expression levels of serum resistin in SLE patients are significantly increased and positively correlated with SLE disease activity and urine protein.Serum resistin may become a novel biomarker for the diagnosis and therapeutic effect assessment of SLE.

Objective:To explore the clinical application value of spiral computed tomography(CT)three-dimensional(3D)scanning reconstruction combined with 3D printing technique in surgery for acetabular fracture.Methods:A total of 71 patients with acetabular fractures admitted to Xinjiang Uiger Municipal People's Hospital from January 2018 to December 2020,who underwent surgical treatment,were selected as the research objects.According to different treatment methods,they were divided into observation group(38 cases)and control group(33 cases).The observation group adopted spiral CT 3D reconstruction,and 3D printing was used to assist the treatment of internal fixation,and the control group adopted conventionally surgical treatment.And then,the surgical effect and recovery situation of the two groups were compared.Results:The quality score(Malta)of fracture reduction and the hip score of sub-item percentile of observation group were significantly higher than those of the control group,and the intraoperative blood loss,the times of intraoperative fluoroscopy,the operation time and hospitalization time of observation group were significantly lower than those of control group(t=23.426,4.216,3.425,17.783,P<0.05),respectively.There was significant difference in the excellent rate of fracture reduction between two groups(x2=4.059,P<0.05).The pain,function and joint activity scores of hip joint function scores of patients in observation group were significantly higher than those of control group(t=-4.873,-5.776,-6.247,P<0.05),respectively.The incidence of complications in observation group was significantly lower than that in control group(x2=4.059,P<0.05).Conclusion:In the perioperative period,the application of spiral CT 3D reconstruction combined with 3D printing of acetabular fractures can further ensure the safety and feasibility of the operation,and improve the quality and efficiency of the surgery,and promote postoperative recovery.

Objective:To investigate the role and underlying mechanisms of inhibiting high mobility group box-1 (HMGB1) in the expression of matrix metalloproteinase-9 (MMP-9) in spinal cord astrocytes (AS) in rats after spinal cord injury (SCI).Methods:After an SCI model was established in Sprague-Dawley (SD) rats using a modified Allen's Weight-Dropping method and ethyl pyruvate (EP) or glycyrrhizin (GL) was used to inhibit the effect of HMGB1, the rats were divided into a sham group, an SCI group, an SCI+EP (50 mg/kg) group, and an SCI+GL (100 mg/kg) group. The expression levels of glial fibrillary acid protein (GFAP) and MMP-9 in spinal cord AS were observed. After the spinal cord AS in SD rats was cultured and incubated by the oxygen-glucose deprivation/reoxygenation (OGD/R) procedure, the expression of MMP-9 protein was detected at 6 h/R 6 h, 12 h, 24 h, and 48 h after OGD. The time point with the highest expression was chosen in the subsequent experiments as an OGD/R group. HMGB1 was inhibited by HMGB1 shRNA or EP to observe the effect of HMGB1 on the expression of MMP-9 protein in AS treated with OGD/R. Then, toll-like receptor 4 (TLR4) inhibitor, TIR-domain-containing adaptor inducing interferon- β (TRIF) inhibitor, and nuclear factor-kappa B (NF- κB) inhibitor were used to investigate the effects of TLR4/TRIF/NF- κB signaling pathway during the regulation of HMGB1 on MMP-9 in vitro. Results:Western blot showed that the expression of MMP-9 protein in the spinal cord was significantly increased in rats at 1 d after SCI, and the expression of MMP-9 protein in the SCI+EP group and the SCI+GL group was significantly lower than that in the SCI group ( P<0.001). Immunofluorescence showed that GFAP and MMP-9 proteins were co-localized in the spinal cord after SCI, and the expression of GFAP and MMP-9 proteins in the SCI+EP and SCI+GL groups was significantly lower than that in the SCI group ( P<0.05). Since the expression of MMP-9 protein in the spinal cord AS cultured in vitro was significantly higher in the OGD 6h/R 12h group than that in the normal group and the OGD 6h/R 6h, 24, and 48 h groups, the OGD 6h/R 12h was taken as the OGD/R group. The MMP-9 protein expression in AS in the OGD/R+HMGB1 shRNA group and the OGD/R+EP group was significantly lower than that in the OGD/R group ( P<0.001). In the cultured AS, moreover, inhibiting TLR4, TRIF, and NF- κB reduced MMP-9 protein expression after OGD 6 h/R 12 h when compared with that in the OGD/R group ( P<0.001). Conclusions:HMGB1 inhibition may result in a reduction in MMP-9 expression both in the spinal cord AS in SCI rats and in AS after OGD/R treatment in vitro. HMGB1 may regulate MMP-9 protein expression in AS after OGD/R treatment via the TLR4/TRIF/NF- κB signal pathway.