ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids （SCFAs） and high mobility group protein B1 （HMGB1）/receptor of advanced glycation end products （RAGE） signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group，model group，low-dose modified Sini San group （7.34 g·kg^-1·d^-1），high-dose modified Sini San group （14.68 g·kg^-1·d^-1），and Fructo-oligosaccharides group （3.15 g·kg^-1·d^-1），with 10 rats in each group. Except for the control group，all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling，each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors，body weight，Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin （HE） staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry （GC-MS）. Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1，Occludin，and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay （ELISA）. ResultsCompared with the model group，the sucrose preference rate，total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased （P<0.05， P<0.01），and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced （P<0.05， P<0.01）. Meanwhile，the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased （P<0.05）. The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased，with a obviously increase in the content of acetic acid，propionic acid，butyric acid，and isovaleric acid （P<0.05， P<0.01） and the expression levels of HMGB1，RAGE，Toll-like receptor 2（TLR2），Toll-like receptor 4（TLR4），tumor necrosis factor-α（TNF-α），and nuclear factor kappa-B p65（NF-κB p65） proteins in cecal tissue were significantly decreased （P<0.05， P<0.01） in low-dose group of modified Sini San. Meanwhile，the contents of ZO-1，Occludin，and Claudin-1 in the cecal tissue were obviously increased （P<0.01） in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.

Objective:To observe the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)in tumor tissue and peripheral blood CD8+T cells in patients with triple-negative breast cancer(TNBC),and to explore the ef-fect of tiragolumab on the function of CD8+T cells in the peripheral blood of these patients.Methods:The expression of TIGIT in tumor tissue of patients with TNBC was analyzed using The Cancer Genome Atlas(TCGA)database and immunohistochemical staining.Flow cytometry was employed to assess the co-expression of TIGIT and programmed death-1(PD-1)in peripheral blood CD8+T cells,as well as their cytokine secretion.A co-culture model of CD8+T cells and TNBC cell lines,HCC-1937 and MDA-MB-231,was estab-lished.The effect of tiragolumab on the anti-tumor activity of CD8+T cells in patients with TNBC was investigated using flow cytometry and confocal fluorescence imaging.Results:The expression of TIGIT in tumor tissue and peripheral blood CD8+T cells of patients with TNBC was significantly increased(P<0.05).Compared with the healthy control group,the TNBC group showed a significantly larger number of TIGIT+PD-1+CD8+T cells in the peripheral blood and significantly reduced secretion of interferon gamma(IFN-γ),tumor necrosis factor-α(TNF-α),and ginkgolide B(GB)by CD8+T cells;specifically,TIGIT+CD8+T cells demonstrated significantly re-duced secretion compared with TIGIT-CD8+T cells(P<0.05).Fol-lowing treatment with tiragolumab,TIGIT+CD8+T cells exhibited increased secretion of IFN-γ and TNF-α(P<0.05).In the co-culture model,tiragolumab restored the apoptosis-inducing ability of CD8+T cells in patients with TNBC,and this ability was further enhanced when it was combined with envafolimab.Conclusion:Ti-ragolumab restores the tumor-killing function of CD8+T cells by im-proving their immunosuppression.The combination of tiragolumab with envafolimab can further enhance its anti-tumor effect.

ObjectiveUltra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS） coupled with network pharmacology and molecular docking was utilized to explore the efficacy and mechanism of action of Ermiao Situ decoction on rats with damp-heat eczema. MethodsA rat model of damp-heat eczema was established by artificial climate chamber intervention combined with sensitization induction by dinitrochlorobenzene （DNCB）， and it was randomly divided into the normal group， the model group， the medium- and high-dose groups of Ermiao Situ decoction （3.40 g·kg^-1 and 6.80 g·kg^-1）， and the prednisone acetate group （2.51 mg·kg^-1）， with eight rats in each group， totalling 46 rats， of which six rats were tested with the drug-containing serum. The chemical analysis of drug-containing serum from rats was carried out by UPLC-Q-TOF-MS/MS， combined with network pharmacology for the prediction of key components， core targets， and signaling pathways， and molecular docking experiments were performed by CB-Dock2 online website. The pharmacological effects of Ermiao Situ decoction in the treatment of damp-heat eczema were investigated by epitaxial indexes combined with the pathologic tissue staining method. The serum levels of gastrin （GAS）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured by enzyme-linked immunosorbent assay （ELISA）. Interleukin-6 （IL-6）， Janus kinase 1 （JAK1）， phosphorylated （p）-JAK1， signal transduction and activation of transcription factor 3 （STAT3）， and p-STAT3 protein expression level was determined by Western bolt. ResultsA total of 19 active ingredients were detected in drug-containing serum samples of rats， which were predicted to act on 198 targets for the treatment of damp-heat eczema， among which the key ingredients included rhodopsin， huangpai alkaloids， and quercetin， and the main core targets included STAT3， tumor necrosis factor （TNF）， and IL-6， which were mainly involved in the cancer signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase （Akt） signaling pathway， T helper 17 （Th17） cell differentiation signaling pathway， and JAK/STAT signaling pathway. The molecular docking results suggested that the key components had strong binding activities with the core targets IL-6， JAK1， and STAT3 in the JAK/STAT signaling pathway. The results of animal experiments showed that compared with those in the normal group， rats in the model group were depressed. They had loose hair， loose stools， epidermal oozing， vesiculation， and generation of thick scabs in the form of scales， decreased body weight， increased anus temperature and water intake， and increased indexes of the spleen， thymus gland， and stomach （P<0.05， P<0.01）， and the lesion tissue could be seen to be hyperkeratotic， with the aggregation of inflammatory cells and nonsignificant separation of epidermis and dermis. The gastric mucosa was thinned， deficient， and structurally disorganized， and obvious inflammatory cell aggregation was seen. The levels of GAS， IL-4， and IL-13 in serum were significantly reduced （P<0.05， P<0.01）， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the lesion tissue were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， rats in each administration group had stable mental states， formed feces， a clean perianal area， and basically normal epidermis. Only a small amount of scaly scabs existed， and the rats had body weight increased， with decreased anal temperature and water intake， as well as decreased spleen， thymus， and gastric indexes （P<0.05， P<0.01）. Epidermal thickness was decreased， and epidermal and dermal separation boundaries were obvious， but hyperkeratotic and accumulation of inflammatory cells could still be seen. The thickness of gastric mucosa increased， and the structure was restored to varying degrees. The levels of GAS， IL-4， and IL-13 content in the serum of rats were increased to varying degrees， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the dermal lesion tissue were significantly decreased （P<0.05， P<0.01）. ConclusionErmiao Situ decoction may exert therapeutic effects on rats with damp-heat eczema by modulating the JAK/STAT signaling pathway.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

Objective: To establish and validate a whole blood (WB) supply model, thereby providing practical experience for the clinical application of WB in domestic trauma emergency care and informing the development of a wartime blood supply system for the military. Methods: A “10×24” WB supply model was established by formulating blood collection protocols, storage standards, and transfusion criteria. Multiple WB samples were tested under specific storage conditions to assess key indicators at different time points, including red blood cell (RBC), white blood cell (WBC), and platelet counts, hemoglobin concentration, coagulation parameters (PT, APTT, TT, FIB), coagulation factor activity, thromboelastography (TEG) parameters, and electrolyte levels. Additionally, clinical data from hemorrhagic patients who met the criteria for WB transfusion and were admitted between March and July 2024 were analyzed to evaluate WB transfusion volume. Results: RBC counts and hemoglobin levels remained stable in WB stored at 4℃ for up to 10 days. However, platelet counts and coagulation function (PT, APTT) significantly declined with prolonged storage, while potassium levels increased. From March to July 2024, the model was successfully applied to 23 patients with acute hemorrhage, with a median WB transfusion volume of 543 mL. A detailed case study of a severe traumatic hemorrhagic shock patient was reported, who was successfully treated with 5.5 units of refrigerated WB combined with component blood. Conclusion: The “10×24” WB supply model demonstrated acceptable changes in critical quality parameters under strict management and a 10-day rotation cycle. This model effectively supports the treatment of acute hemorrhage and holds promise for integration into the future wartime blood supply system of the military.

Objective:To explore the impacts of acupuncture and moxibustion combined with ABCLOVE voice training on voice function and the levels of inflammatory factors in patients who were diagnosed with vocal cord polyp and received operation. Methods:A total of 96 cases who received operation on vocal cord polyp were randomly assigned into two groups. The control group was given ABCLOVE voice training for rehabilitation after the operation. The study group was given acupuncture and moxibustion combined with ABCLOVE voice training. The voice function and the levels of inflammatory factors of the two groups were compared. Results:The effective rate of the study group was higher than that of the control group（P<0.05）. The scores of main symptoms such as hoarseness, dry mouth, and thirst in the study group were lower than those in the control group（P<0.05）. After 4 weeks of treatment, the voice fundamental frequency（F0） of the study group was higher than that of the control group（P<0.05）, the maximum phonation time（MPT） was longer than that of the control group（P<0.05）, and the voice fundamental frequency perturbation value（Jitter） and voice amplitude perturbation value（Shimmer） were lower than those of the control group（P<0.05）. The levels of serum interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） were lower than those of the control group（P<0.05）. Conclusion:Acupuncture and moxibustion combined with ABCLOVE voice training can obviously alleviate hoarseness and other symptoms, improve voice function and reduce the level of inflammatory factors, thus is an effective treatment for patients who received operation on vocal cord polyp.
Humans ; Moxibustion ; Polyps/therapy* ; Vocal Cords ; Acupuncture Therapy ; Voice Training ; Female ; Male ; Adult ; Middle Aged ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Young Adult ; Laryngeal Diseases/therapy*

Through studying Chen Yiren's works,this paper summarizes Chen Yiren's academic thought of diligently seeking and learning,thinking about the purpose of the classics,exploring the essence of the theory,and studying the prescriptions and techniques,and expounds Chen Yiren's experience of"learning,studying,distinguishing,and applying"Treatise on Cold Damage.Professor Chen Yiren advocates the combined theory of external and internal injuries,the"six meridians regulating all diseases"theory,and"bad dis-eases being difficult and complicated diseases"theory.His thought on studying is reflected in the following four aspects:learn,dili-gently seeking and learning,and teaching people the law,citing evidence from various schools,distinguishing syndromes and seeking causes,connecting with clinical practice,and summarizing the three methods of selecting prescriptions;research,thinking about the purpose of the classics and explaining the key points,summarizing the five major characteristics of Treatise on Cold Damage of"differ-entiation,change,strictness,flexibility,and simplicity",explaining that Yangming disease has no distinction between meridians and viscera,and emphasizing the combination of pulse and syndromes;distinguish,exploring the principles,distinguishing doubts and re-solving confusion,revealing the rules of diagnosis and treatment of bad diseases,showing people the"living"method,discussing the prescriptions and syndromes of Jueyin disease,and focusing on applying the ancient to the present;apply,studying the prescriptions and techniques carefully and differentiating flexibly,explaining that the six meridians regulates hundreds of diseases,distinguishing complex and difficult diseases and syndromes,clarifying the complications and suspected syndromes,using the differentiation method flexibly,and opening up ideas for the use of classic prescriptions.In addition,Chen Yiren emphasizes the important position of the Treatise on Cold Damage course in TCM education and talent training,which should be strengthened during education and teaching as well as curriculum construction,making great contributions to the inheritance and development of Treatise on Cold Damage.

AIM:This study aimed to utilize network pharmacology and an anxiety rat model to investigate the intervention targets and underlying mechanisms of Baixiangdan capsule(BXD)in the treatment of anxiety-like behavior.METHODS:We screened the action targets of BXD on the anxiety model using network pharmacology,followed by Gene Ontology(GO)enrichment and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the identified targets.Additionally,we evaluated the effects of BXD on rat anxiety behaviors induced by foot shock,with measurement of serum level of c-Jun N-terminal kinase inhibitor(JIK),and the protein levels of c-Jun N-terminal kinase(JNK),phos-phorylated JNK(p-JNK)and JIK in the left hippocampus and hypothalamus.RESULTS:A total of 97 targets,including the dopamine D1/D3 receptors,were identified as intersection targets.GO enrichment analysis indicated that target pro-teins were significantly involved in molecular functions such as catecholamine binding,receptor activation,and signal transduction.KEGG pathway analysis revealed that neural receptor-ligand pathways,including dopaminergic synapses(15%)and neuroactive ligand-receptor interaction(18%),were notably represented.In behavioral experiments,BXD and diazepam treatments significantly reduced total path in the open-field test(P＜0.01),while the number of entries into the central region increased(P＜0.05).Additionally,the percentage of entry times of the open arm and the percentage of time spent in the open arm were also increased(P＜0.01).Furthermore,BXD treatment led to decreased ratio of p-JNK/JNK and increased level of JIK(P＜0.05).CONCLUSION:The traditional Chinese medicine BXD demonstrates a promising efficacy in alleviating anxiety-like behaviors in model rats.It operates through a multi-component,multi-target,and multi-pathway approach,primarily by modulating the JIK/JNK signaling pathway.

Objective:To explore the effect of autologous vascular graft bridging of the popliteal artery defect to reconstruct the blood supply of leg on survival of lower extremity.Methods:From May 2021 to May 2024, 10 patients with traumatic popliteal artery injury with defect were treated in the Department of Hand and Foot Surgery, Nanhua Hospital Affiliated to University of South China. A retrospective analysis was conducted on clinical data of the patients. Injury sites were: 6 in left lower extremity and 4 in right lower extremity. Causes of injury were: 4 of traffic accident, 2 of heavy object compression, 2 of electric saw, and 2 of falling from heights. Sixe patients had large vessel injury combined with fracture and (or) knee dislocation, and 4 had simple large vessel injury. Six patients had open vascular injury and 4 had closed vascular injury. There were 6 popliteal artery defect and 4 femoral artery defect, with the defects ranging from 5.0 to 10.0 cm in length. Based on the condition of the arterial defect, autologous great saphenous vein (9 patient) and small saphenous vein (1 patient) were taken and prepared to different forms of vascular bridging graft, such as "single crotch-shape" (6 patient), "double crotch-shape" (3 patient) and "triple crotch-shaped" (1 patient) vascular bridging grafts, to have the defects of popliteal artery reconstructed. Scheduled postoperative follow-up was conducted at outpatient clinic and via telephone interviews. Detailed outcomes including the peripheral blood flow, presence of necrosis or ulcer as well as patient satisfaction were recorded.Results:All of the blood vessel anastomoses in 10 patients were successful and the distal blood supply of the affected legs was restored. All of the affective legs survived. Postoperative follow-ups at 3 to 12 months showed good blood flow in the legs without necrosis nor ulcer as well as a high patient satisfaction.Conclusion:The "crotch-shaped" autologous blood vessel graft can timely and effectively reconstruct defected main artery in popliteal fossa, reduce ischemia time of the affected leg, promote extremity survival and restore its function.

Objective:To investigate the impacts of different surgical fixation sequences on the post-operative functional outcomes in patients with ankle fracture combined with Lisfranc injury.Methods:A retrospective study was conducted to analyze the 20 patients with ankle fracture and concomitant Lisfranc injury who had been treated between January 2014 and December 2023 at Department of Orthopedics, The 82nd Group Army Hospital of PLA. The cohort included 16 males and 4 females, with an age of (41.3±12.3) years. Patients were divided into 2 groups based on their surgical sequence: an ankle-first group ( n=12) treated first by open reduction and internal fixation of the ankle fracture and then by additional incision reduction and fixation of the Lisfranc injury, and a foot-first group ( n=8) treated first by open reduction and fixation of the Lisfranc injury and then by another incision for open reduction and internal fixation of the ankle fracture. The surgical time, intraoperative fluoroscopy frequency, postoperative Lisfranc articular step-off, postoperative arch height index (AHI), and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and incidence of traumatic arthritis at 1 year after surgery were compared between the 2 groups. Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (18.3±3.2) months after surgery. There was no statistically significant difference in surgical time or incidence of traumatic arthritis between the 2 groups ( P>0.05). In the ankle-first group, the intra-operative fluoroscopy frequency [(16.6±2.6) times] was significantly higher than that in the foot-first group [(13.6±2.5) times], and the postoperative Lisfranc articular step-off [0.0 (0.0, 0.8) mm], postoperative AHI [0.31 (0.29, 0.32)], and AOFAS ankle-hindfoot score at 1 year after surgery [(85.2±2.2) points] were all significantly better than those in the foot-first group [(1.3±1.3) mm, 0.29±0.01, and (81.0±4.1) points] (all P<0.05). Conclusion:In the treatment of ankle fracture combined with Lisfranc injury, prioritizing ankle fixation provides a stable biomechanical foundation for subsequent midfoot reduction, leading to improved functional recovery and radiographic outcomes, but requires increased intraoperative fluoroscopy.