ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective To compare clinical efficacy of combined external fixator and plate fixation in treating throwing fracture of humerus.Methods Sixty-seven male patients with throwing humerus fracture admitted from February 2018 to February 2021 were retrospectively analyzed and divided into external fixator group and plate group according to different treatment methods.There were 32 patients in external fixator group,aged from 18 to 27 years old with an average of(23.6±2.6)years old;19 patients with type A,13 patients with type B according to AO classification;fixed by combined external fixer.There were 35 patients in plate group,aged from 17 to 28 years old with an average of(23.2±2.9)years old;21 patients with type A,14 patients with type B according to AO classification;fixed with steel plate screws.Operation time,intraoperative blood loss,total incision length,fracture healing time and complications were compared between two groups.Clinical effect was evaluated by Mayo elbow performance score(MEPS)and shoulder Neer score at 12 months after operation.Results Patients in both groups were successfully completed operation and followed up for 15 to 21 months with an average of(18.3±3.4)months.In external fixator group,intraoperative blood loss,incision length,fracture healing time and postoperative MEPS of el-bow joint function at 12 months were(68.5±15.7)ml,(4.9±1.2)cm,(10.5±2.9)weeks,(93.6±5.1)min,respectively;which were superior to ml(149.4±38.9)ml,(12.5±2.4)cm,(12.8±2.7)weeks,(85.6±6.8)in plate group(P＜0.05),and had signif-icant differences;there were no significant difference in operative time and postoperative Neer score of shoulder joint function at 12 months between two groups(P＞0.05).There were 6 patients occurred radial nerve injury in plate group and no patient occurred radial nerve injury in external fixator group,and the difference between two groups was statistically significant(x2=6.025,P＜0.05).There were no significant difference in postoperative MEPS grading and Neer shoulder joint grading at 12 months(P＞0.05).Bone healing was achieved in both groups without failure of internal fixation.Conclusion The combined ex-ternal fixator for the treatment of humerus throwing fracture has characteristics of low incidence of radial nerve injury,less bleeding,less complications,fast fracture healing,which is convenient to remove after fracture healing.

Pancreatic cancer is highly aggressive and often diagnosed at an advanced stage,leaving most patients ineligible for radical resection.This study retrospectively analyzed four patients with locally advanced or advanced pancreatic cancer to evaluate the clinical efficacy and safety of high-intensity focused ultrasound(HIFU)ablation combined with chemotherapy as a neoadjuvant and conversion therapy.All cases were reviewed and individualized treatment plans were formulated through a multidisciplinary team evaluation.All patients received HIFU plus gemcitabine and nab-paclitaxel chemotherapy,with assessments of tumor volume,vascular involvement,surgical conversion,symptom relief,and adverse events.Three patients achieved marked tumor shrinkage and reduction of vascular invasion,enabling successful R0 resection without recurrence during follow-up.The remaining patient achieved disease stability,significant pain relief,and maintained good quality of life under repeated HIFU therapy.All treatments were well tolerated,and no severe adverse reactions occurred.The combination of HIFU and chemotherapy demonstrated synergistic local and systemic effects,effectively achieving tumor downstaging,improving resectability,and alleviating symptoms.As a safe,noninvasive,and repeatable therapeutic approach,this strategy offers a promising option for patients with advanced pancreatic cancer.Further large-scale prospective studies are warranted to validate its long-term efficacy and elucidate underlying mechanisms.

OBJECTIVE: Prunella vulgaris L. has long been used for liver protection according to traditional Chinese medicine theory and has been proven by modern pharmacological research to have multiple potential liver-protective effects. However, its effects on non-alcoholic steatohepatitis (NASH) are currently uncertain. Our study explores the effects of P. vulgaris polysaccharides on NASH and intestinal homeostasis. METHODS: An aqueous extract of the dried fruit spikes of P. vulgaris was precipitated in an 85% ethanol solution (PVE85) to extract crude polysaccharides from the herb. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was administrated to male C57BL/6 mice to establish a NASH animal model. After 4 weeks, the PVE85 group was orally administered PVE85 (200 mg/[kg·d]), while the control group and CDAHFD group were orally administered vehicle for 6 weeks. Quantitative real-time polymerase chain reaction analysis, Western blotting, immunohistochemistry and other methods were used to assess the impact of PVE85 on the liver in mice with NASH. 16S rRNA gene amplicon analysis was employed to evaluate the gut microbiota abundance and diversity in each group to examine alterations at various taxonomic levels. RESULTS: PVE85 significantly reversed the course of NASH in mice. mRNA levels of inflammatory mediators associated with NASH and protein expression of hepatic nucleotide-binding leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) were significantly reduced after PVE85 treatment. Moreover, PVE85 attenuated the thickening and cross-linking of collagen fibres and inhibited the expression of fibrosis-related mRNAs in the livers of NASH mice. Intriguingly, PVE85 restored changes in the gut microbiota and improved intestinal barrier dysfunction induced by NASH by increasing the abundance of Actinobacteria and reducing the abundance of Proteobacteria at the phylum level. PVE85 had significant activity in reducing the relative abundance of Clostridiaceae at the family levels. PVE85 markedly enhanced the abundance of some beneficial micro-organisms at various taxonomic levels as well. Additionally, the physicochemical environment of the intestine was effectively improved, involving an increase in the density of intestinal villi, normalization of the intestinal pH, and improvement of intestinal permeability. CONCLUSION PVE85 can reduce hepatic lipid overaccumulation, inflammation, and fibrosis in an animal model of CDAHFD-induced NASH and improve the intestinal microbial composition and intestinal structure. Please cite this article as: Zhu MJ, Song YJ, Rao PL, Gu WY, Xu Y, Xu HX. Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis. J Integr Med. 2025; 2025; 23(3): 297-308.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Male ; Dysbiosis/drug therapy* ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects* ; Polysaccharides/therapeutic use* ; Prunella/chemistry* ; Mice ; Liver/metabolism* ; Plant Extracts/therapeutic use* ; Disease Models, Animal ; Diet, High-Fat

Protein tyrosine phosphatases (PTPs, EC 3.1.3.48) are key regulators of cellular processes, with the catalytic activity attributed to the conserved motif (H/V)CX₅R(S/T), where cysteine and arginine residues are critical. Previous studies revealed that alternative splicing of extracellular phosphatase mRNA precursors in Metarhizium anisopliae generated two distinct transcripts, with the longer sequence containing a novel HCPTPMLS motif resembling PTP signatures but lacking the arginine residue. To identify the novel signature motif and characterize its enzymatic properties, we heterologously expressed and purified both proteins in Pichia pastoris and comprehensively characterized their enzymatic properties. The protein containing the HCPTPMLS motif (designated as L-protein) exhibited the highest activity at pH 5.5 and a strong preference for pTyr substrates. Its phosphatase activity was inhibited by Ag⁺, Zn²⁺, Cu²⁺, molybdate, and tungstate, but enhanced by Ca²⁺ and EDTA. AcP101 (lacking HCPTPMLS) showed the maximal activity at pH 6.5 and a strong preference toward pNPP (P < 0.05), with the activity inhibited by NaF and tartrate, but enhanced by Mg²⁺ and Mn²⁺. Functional analysis confirmed that the L-protein retained the PTP activity despite the absence of arginine in its signature motif, while AcP101 functioned as an acid phosphatase. This study provides the first functional validation of an arginine-deficient PTP motif, expanding the definition of PTP signature motifs and offering new insights for phosphatase classification.
Metarhizium/genetics* ; Protein Tyrosine Phosphatases/chemistry* ; Amino Acid Motifs ; Recombinant Proteins/biosynthesis* ; Amino Acid Sequence ; Pichia/metabolism* ; Fungal Proteins/chemistry* ; Substrate Specificity ; Saccharomycetales

Objective:This study aimed to analyze the genetic subtypes and drug resistance transmission characteristics of HIV-1 among the preoperative population in Ningxia from 2018 to 2023, to provide a scientific basis for the prevention and control of the AIDS epidemic.Methods:Plasma samples and demographic information of HIV/AIDS patients receiving antiviral treatment in Ningxia from 2018 to 2023 were collected. Blood samples with a viral loads >200 copies/ml from preoperative testing were amplified, sequenced, and subjected to genotypic resistance testing to analyze their genetic subtypes and drug resistance characteristics. The TN93 model in MEGA11 software was used to calculate the genetic distance between each pair of all sequences, and a molecular transmission network was constructed in Cytoscape 3.10.0 with 1.9% as the genetic threshold.Results:Among 101 preoperative HIV/AIDS patients, CRF07_BC and CRF01_AE were the predominant subtypes. The majority were male (85.15%, 86/101), aged 41-60 years (45.54%, 46/101), residing in Yinchuan city (61.39%, 62/101), and infected via heterosexual transmission (71.29%, 72/101), with most cases being late-detected. Of 39 drug-resistant sequences, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) alone (18.81%, 19/101) and dual resistance to nucleoside reverse transcriptase inhibitors (NRTIs)-NNRTIs (13.86%, 14/101) were most common. Among 44 sequences forming 13 transmission clusters, nine clusters harbored drug-resistant mutations. Four subtypes entered the molecular network, primarily involving heterosexual transmission, individuals with junior high school education or below, and men aged≥50 years.Conclusions:From 2018 to 2023, the preoperative HIV/AIDS patients had diversified genetic subtypes, with higher rates of overall drug resistance and late detection, stronger drug resistance and higher mortality rate. Strengthening molecular epidemiological research and developing targeted screening strategies are critical to improve early detection and reduce transmission risks.

Objective To compare clinical efficacy of combined external fixator and plate fixation in treating throwing fracture of humerus.Methods Sixty-seven male patients with throwing humerus fracture admitted from February 2018 to February 2021 were retrospectively analyzed and divided into external fixator group and plate group according to different treatment methods.There were 32 patients in external fixator group,aged from 18 to 27 years old with an average of(23.6±2.6)years old;19 patients with type A,13 patients with type B according to AO classification;fixed by combined external fixer.There were 35 patients in plate group,aged from 17 to 28 years old with an average of(23.2±2.9)years old;21 patients with type A,14 patients with type B according to AO classification;fixed with steel plate screws.Operation time,intraoperative blood loss,total incision length,fracture healing time and complications were compared between two groups.Clinical effect was evaluated by Mayo elbow performance score(MEPS)and shoulder Neer score at 12 months after operation.Results Patients in both groups were successfully completed operation and followed up for 15 to 21 months with an average of(18.3±3.4)months.In external fixator group,intraoperative blood loss,incision length,fracture healing time and postoperative MEPS of el-bow joint function at 12 months were(68.5±15.7)ml,(4.9±1.2)cm,(10.5±2.9)weeks,(93.6±5.1)min,respectively;which were superior to ml(149.4±38.9)ml,(12.5±2.4)cm,(12.8±2.7)weeks,(85.6±6.8)in plate group(P＜0.05),and had signif-icant differences;there were no significant difference in operative time and postoperative Neer score of shoulder joint function at 12 months between two groups(P＞0.05).There were 6 patients occurred radial nerve injury in plate group and no patient occurred radial nerve injury in external fixator group,and the difference between two groups was statistically significant(x2=6.025,P＜0.05).There were no significant difference in postoperative MEPS grading and Neer shoulder joint grading at 12 months(P＞0.05).Bone healing was achieved in both groups without failure of internal fixation.Conclusion The combined ex-ternal fixator for the treatment of humerus throwing fracture has characteristics of low incidence of radial nerve injury,less bleeding,less complications,fast fracture healing,which is convenient to remove after fracture healing.

Objective:To compare and observe the fundus imaging characteristics of eyes with glucocorticoid-related central serous chorioretinopathy (CSC).Methods:A retrospective clinical study. A total of 149 CSC patients with 166 eyes diagnosed at Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University from March 2021 to October 2024 were included in the study. The duration of the disease from the appearance of symptoms to treatment was less than 3 months. All affected eyes underwent best-corrected visual acuity (BCVA), fundus color photography, swept-source optical coherence tomography (SS-OCT), and fundus fluorescein angiography (FFA) examinations. BCVA was tested using an international standard vision chart and converted into logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. The SS-OCT instrument measured subfoveal choroidal thickness (SFCT), central macular thickness (CMT), choroidal vascular volume (CVV), and the width and height of flat irregular pigment epithelial detachment (FIPED). FIPED, subretinal fibrin, and choroidal layer strong reflective spots were identified from SS-OCTA B-scan images; multiple leakages (leak points >3) were identified from FFA images. Based on the presence or absence of a clear history of glucocorticoid administration before the onset, patients were divided into glucocorticoid-related and non-glucocorticoid-related groups, comprising 41 patients with 53 eyes and 108 patients with 113 eyes, respectively. Clinical and fundus imaging characteristics of the two groups were compared. The comparison of quantitative data between the two groups was performed using independent samples t test or non-parametric independent samples Wilcoxon test; the comparison of qualitative data was performed using χ2 test. Results:Compared with the non-glucocorticoid-related group, the glucocorticoid-related group had a smaller male-to-female ratio and a higher bilateral incidence, and the differences were statistically significant ( χ2=4.925, 17.849; P<0.05). The logMAR BCVA for the glucocorticoid-related and non-glucocorticoid-related groups were 0.45±0.33 and 0.21±0.21, respectively; SFCT were (644.43±131.91) and (507.26±121.79) μm; CMT were (389.51±233.45) and (362.59±140.85) μm; CVV were (4.44±1.07) and (3.67±0.82) mm 3; FIPED incidence were 58.49% (31/58) and 20.35% (23/113), respectively; FIPED width and height were (1 122.01±533.98) and (742.90±388.79) μm, and (99.13±92.17) and (33.01±15.99) μm; subretinal fibrin were observed in 24 (45.28%, 24/53) and 15 (13.27%, 15/113) eyes; choroidal strong reflections were found in 38 (71.70%, 38/53) and 45 (39.82%, 45/113) eyes; multiple leak points were identified in 35 (66.03%, 35/53) and 40 (35.40%, 40/113) eyes, respectively. Compared with the non-glucocorticoid-related group, the glucocorticoid-related group had worse BCVA ( Z=-4.984), thicker SFCT ( t=6.586), larger CVV ( t=5.160), higher incidence of FIPED ( χ2=23.908), and greater width and height of FIPED ( t=2.895, Z=-3.703). The glucocorticoid-related group also had a significantly increased incidence of subretinal fibrin, choroidal strong reflections, and multiple leak points, with all differences being statistically significant ( χ2=20.565, 14.663, 13.675; P<0.05); however, the comparison of CMT showed no statistically significant difference ( Z=-0.651, P>0.05). Conclusion:Compared with non-glucocorticoid-related CSC, glucocorticoid-related CSC patients have poorer vision, are more likely to affect both eyes, show no gender bias; choroidal vascular dilation is more significant, and damage to the outer retina and retinal pigment epithelium is more severe.

In this work,near infrared carbon quantum dots(NIR-CDs)were synthesized by hydrothermal method using biomass material Clausena lansium leaves.The synthesized NIR-CDs emitted maximum fluorescence signal at 677 nm,which was independent of excitation wavelength.The characterization results showed that there were abundant groups on the surface of NIR-CDs.Pd2+could form non-fluorescent compounds with the surface groups of NIR-CDs,resulting in fluorescence quenching(Fluorescence signal was denoted as F0).Because chlorpromazine hydrochloride(CPZ)parent nucleus contained unoxidized S atom,CPZ could form stable colored complex with Pd2+under acidic conditions.In the presence of CPZ,Pd2+dissociated from the surface of NIR-CDs and bonded with CPZ,so that the fluorescence signal could be restored(Fluorescence signal was denoted as F).An"on-off-on"fluorescence sensor was thus constructed.The fluorescence signal recovery value of NIR-CDs(△F=F-F0)showed a good linear relationship with the concentration of CPZ in the range of 5.68-28.43 μg/mL,and the detection limit(3σ)was 0.078 μg/mL.The sensor was applied to determination of CPZ in pharmaceutical preparations,and the recoveries were 94％-106％.The developed fluorescence sensor was expected to be used in quality control of actual pharmaceutical preparations.