ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Dampness-heat syndrome of the spleen and stomach refers to the evil dampness-heat invading the spleen and stomach,the abnormal rise and fall of the middle jiaoqi machinery,dampness-heat depression and steaming,the physiological dysfunction of the spleen and stomach,with abdominal distention and distention,nausea and lethargy of the limbs,poor loose stool,red tongue and yellow greasy fur,and slippery pulse as the main symptoms of the syndrome,most common in digestive system diseases,among which chronic gastritis is the first.This paper summarized the research results in the past decade and related fields.In the mode of combination of disease and syndrome,based on the principle of corresponding prescription and syndrome,combined with the etiology and pathogenesis evolution of spleen and stomach damp-heat syndrome,the biological connotation of spleen and stomach damp-heat syndrome was explained from various aspects such as inflammation and immune disorders,gastrointestinal motivity disorders,water and humidity loss,endoplasmic reticulum function,and micro-ecological disorders.Enrich the research of the essence of syndrome.

AIM To study the chemical constituents from Gymnema tingens Spreng.and their in vitro hypoglycemic activity.METHODS The 70％ethanol extract was isolated and purified by macroporous resin,silica gel,sephadex LH-20,and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical propeties and spectral data.The in vitro hypoglycemic activity was evaluated by glucose uptake test in L6 cells.RESULTS Seventeen compounds were isolated and identified as 7-desoxyneocynapanogenin A(1),glaucogenin(2),cynatratoside A(3),atratcynoside F(4),(+)-lyoniresinol(5),(+)-lyoniresinol 3-O-α-D-rhamnopyranoside-(1→6)-β-D-glucopyranoside(6),fernandoside(7),3,4-dimethoxy-phenyl-1-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside(8),khaephuoside A(9),khaephuoside B(10),3,4,5-trimethoxy-phenyl-O-β-D-glucopyranoside(11),liquiritigenin(12),7,3'-dihydroxy-flavanone-4'-O-β-D-glucopyranoside(13),pinoresinol(14),syringaldehyde(15),(+)-1-hydroxy-pinoresinol-1-β-D-glucopyranoside(16),β-amyrin(17).Compounds 2-5、7、9、10、12、17 could promote the glucose uptake in L6 cells.CONCLUSION Compound 1 is a new compound,and 2-9、11-13、15-17 are isolated from this plant for the first time.Compounds 2-5、7、9、10、12、17 have good hypoglycemic activity.

OBJECTIVE To explore the molecular mechanism of Xijiao Dihuang Decoction(XJDHT)in inhibiting inflammatory response in sepsis based on network pharmacology,molecular docking and in vitro and in vivo experiments.METHODS Active com-ponents of XJDHT were screened using the TCMSP and HERB databases.Sepsis-related targets and histone H3K36 trimethylation(H3K36me3)-associated targets were retrieved from GeneCard,OMIM,and DisGeNet databases.A protein-protein interaction(PPI)network was constructed using the STRING database,and core targets were identified via Cytoscape 3.9.1.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to predict potential mechanisms.Mo-lecular docking validated ligand-receptor binding affinity.A cecal ligation and puncture(CLP)model was established in mice to evalu-ate 24-hour sepsis scores(MSS)and survival rates.Blood routine parameters were analyzed using an automated hematology analyzer.Serum IL-1β and TNF-α levels were measured by ELISA.Liver histopathology was assessed via HE staining,and H3K36me3 expression in Kupffer cells was detected by immunofluorescence.In vitro,LPS-induced THP-1 cells were used as an in-flammatory model.ChIP-qPCR evaluated H3K36me3 enrichment at IL-1β and TNF-α gene loci.Western blot analyzed HIF-1α,EGFR,and AKT1 pathway proteins.RESULTS A total of 28 active components of XJDHT were identified,corresponding to 987 gene targets,with 189 overlapping sepsis-related targets.Core targets included TNF,IL1B,and GAPDH.Enriched pathways includ-ed EGFR tyrosine kinase inhibitor resistance.Molecular docking confirmed strong binding between core components and key targets.In vivo,compared to the sham group,the CLP group exhibited significantly reduced 24-hour survival(P<0.01),elevated MSS(P<0.01),immune imbalance,and increased serum IL-1β and TNF-α levels(P<0.01).High-and low-dose XJDHT intervention im-proved survival(P<0.01),reduced MSS(P<0.01),restored immune homeostasis,and dose-dependently suppressed IL-1β and TNF-α(P<0.01).CLP mice showed elevated H3K36me3 in Kupffer cells and severe hepatic inflammation,while XJDHT dose-de-pendently reduced H3K36me3(P<0.05)and attenuated liver injury.In peritoneal macrophages,CLP upregulated H3K36me3,IL-1β,TNF-α,HIF-1α,p-AKT1/AKT1,and EGFR(P<0.01),which were reversed by XJDHT(P<0.05,P<0.01).In vitro,LPS increased H3K36me3 and IL-1β and TNF-α expression(P<0.01),with ChIP-qPCR confirming H3K36me3 enrichment at IL-1β lo-ci(P<0.01).Treatment with 15%XJDHT-containing serum for 24 h reduced H3K36me3(P<0.01),diminished its recruitment to IL-1β loci(P<0.01),and inhibited LPS-induced activation of EGFR,HIF-1α,and p-AKT1/AKT1(P<0.05,P<0.01).HIF-1α agonist Dimethyloxallyl Glycine(DMOG)further validated that XJDHT suppressed H3K36me3-mediated epigenetic remodeling via HIF-1α-related pathways.CONCLUSION XJDHT inhibits inflammatory responses,regulates immune homeostasis,and improves sepsis prognosis,potentially by modulating H3K36me3 epigenetic modifications at IL-1β loci.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

Objective To analyze the risk factors for postoperative intra-abdominal infection in gastric cancer pa-tients,as well as construct and validate a nomogram prediction model.Methods 588 gastric cancer surgery pa-tients who admitted to the Department of General Surgery of the First Affiliated Hospital of Soochow University from April 2021 to March 2024 were selected as the study subjects.Clinical data of patients were collected and ran-domly divided into the training set and the validation set according to the ratio of 3∶1.Clinical data between two groups of patients were compared.Patients were divided into the infection group and non-infection group according to whether they had intra-abdominal infection after surgery.Univariate and multivariate analyses were conducted,and a nomogram prediction model was constructed and validated based on the results of multivariate analysis.Results Among the 588 patients,52(8.84％)had postoperative intra-abdominal infection.A total of 65 strains of patho-gens were detected from 52 peritoneal fluid specimens,out of which 47(72.31％)were Gram-negative bacteria,15(23.07％)were Gram-positive bacteria,and 3(4.62％)were fungi.Multivariate logistic regression analysis showed that the degree of eradication(microscopic residue),combined organ resection,hypertension,history of ab-dominal surgery,and duration of surgery were all independent risk factors for postoperative intra-abdominal infec-tion in gastric cancer patients(all P＜0.05).Based on multivariate analysis results,a nomogram prediction model for postoperative intra-abdominal infection in gastric cancer patients was constructed.The receiver operating charac-teristic(ROC)curve result showed that the areas under the ROC curve(AUCs)of the training set and validation set were 0.764(95％CI:0.677-0.852)and 0.712(95％CI:0.565-0.860,respectively,indicating that the model had good discriminability for postoperative intra-abdominal infection in gastric cancer patients.Hosmer-Lemeshow test showed a x2 value of 8.491 and a P value of 0.387,suggesting goodness fit of the model.The decision curve analysis(DCA)result showed that within the risk threshold ranges of the training set(0.05-0.4)and validation set(0.1-1.0,positive benefits may be obtained by using the model to intervene in patients with high risk of post-operative intra-abdominal infection.Clinical impact curve(CIC)analysis result showed that within the risk thresh-old ranges of the training set(0-0.4)and validation set(0-0.5),the number of infected cases predicted by the model was higher than the actual number,indicating good clinical practicality of the model.Conclusion Construc-tion of a nomogram prediction model based on independent risk factors for postoperative intra-abdominal infection in gastric cancer can provide a quantitative and intuitive reference for the early clinical assessment of postoperative in-tra-abdominal infection in gastric cancer.

Objective To investigate the impacts of ultrasound-guided stellate ganglion block(SGB)on hemodynamics and postoperative cognitive function in patients undergoing shoulder arthroscopic surgery.Methods From January 2024 to June 2024,120 patients undergoing shoulder arthroscopic surgery in our hospital were randomly assigned into general anesthesia group(n=60,implementing general anesthesia)and assisted SGB group(n=60,implementing ultrasound-guided SGB combined with general anesthesia).The intraoperative hemodynamics,postoperative stress status[serum cortisol(Cor)and interleukin-6(IL-6)],postoperative pain level[evaluated by visual analogue scale(VAS)score],postoperative biomarkers[serum matrix metalloproteinase-9(MMP-9)and neurospecific protein S-100β(S-100β)],and postoperative cognitive function[evaluated using the mini-mental state examination(MMSE)]were compared between the two groups.Results There was no statistically significant difference in intraoperative blood loss and surgical time between the two groups of patients(P>0.05).After induction of anesthesia(T1),the mean arterial pressure(MAP)and heart rate(HR)of the two groups of patients were significantly lower than when they entered the operating room(T0),the differences were statistically significant(P<0.05).The MAP and HR during the beginning of the surgery(T2),30 min after the start of the surgery(T3),and at the end of the surgery(T4)were higher than those at T0,the differences were statistically significant(P<0.05).While the MAP and HR in the assisted SGB group during T1,T2,T3 and T4 time points were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The VAS scores of the assisted SGB group were significantly lower than those of the general anesthesia group at 12 and 24 h after surgery,and the differences were statistically significant(P<0.05).The levels of serum Cor and IL-6 in the two groups at 12 and 24 h after surgery were higher than those at 1 d before surgery,but the levels of serum Cor and IL-6 in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The levels of serum MMP-9 and S-100β in the two groups at 24 and 72 h after surgery were higher than those at 1 d before surgery(P<0.05),but the levels of serum MMP-9 and S-100β in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The MMSE score of the two groups at 3 and 5 d after surgery were lower than those at 1 d before surgery,but the MMSE score of the assisted SGB group was higher than that of the general anesthesia group,the difference was statistically significant(P<0.05).Conclusion The implementation of ultrasound-guided SGB during shoulder arthroscopic surgery can maintain intraoperative hemodynamic stability,obviously alleviate postoperative stress and pain,obviously reduce serum MMP-9 and serum S-100β levels,and help alleviate postoperative cognitive dysfunction.It is worthy clinical application.