Background Protein tyrosine phosphatase non-receptor type II (PTPN2) is essential for the regulation of inflammation and immunity, but the specific mechanism of action of Ptpn2 in silicosis is unknown. Objective To investigate the regulatory role of overexpression of Ptpn2 in SiO₂-mediated inflammatory response in alveolar type II epithelial cells based on transcriptome sequencing. Methods This study was an in vitro study. A negative control group (vector transferred) and an overexpression of Ptpn2 group of mouse lung epithelial cell line MLE-12 cells were firstly constructed. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs), differentially expressed mRNAs, and differentially expressed ncRNAs in the two groups of MLE-12 cells, and then the DEGs were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Constructed MLE-12 cells and A549 cells were stimulated using SiO₂ suspension, and divided into a negative control group (vector transferred), an overexpression of Ptpn2 group, a negative control + SiO₂ group, and an overexpression of Ptpn2 + SiO₂ group, respectively. Protein expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-17A, IL-2, IL-1β were detected by Western blot. Positive TNF-α expression was detected by immunofluorescence staining. Results The results of Western blot showed that the protein expression level of PTPN2 was up-regulated in the overexpressed Ptpn2 group compared with the negative control group (P < 0.05). The volcano plot and clustering heat map showed that there were 1122 DEGs, 3681 differentially expressed mRNAs, and 474 differentially expressed ncRNAs in the overexpressed Ptpn2 group compared with the negative control group. The results of GO enrichment showed that, in terms of the biological process, the DEGs were mainly related to the regulation of metal ion transport, extracellular matrix organization, and extracellular structural organization; in terms of cellular composition, the DEGs were mainly related to collagen-containing extracellular matrix, receptor complexes, and basement membranes; in terms of molecular function, the DEGs were mainly related to the extracellular matrix structural constituents, glycosaminoglycan binding, and semaphorin receptor binding. The results of KEGG enrichment showed that the DEGs were closely related to cytokin-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, and chemokine signaling pathway. In MLE-12 and A549 cells, the results of Western blot showed that the protein expression levels of TNF-α , IL-17A, IL-2, and IL-1β were up-regulated in the negative control + SiO₂ group compared with the negative control group (P < 0.05), and the protein expression levels of TNF-α, IL-17A, IL-2, and IL-1β were down-regulated in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group (P < 0.05). The immunofluorescence staining showed that the expression of TNF-α was increased in the negative control + SiO₂ group compared with the negative control group, and decreased in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group. Conclusion Overexpression of Ptpn2 inhibits SiO₂-mediated inflammatory response in MLE-12 cells and A549 cells.

Thrombospondin 4 (THBS4; TSP4), a crucial component of the extracellular matrix (ECM), serves as an important regulator of tissue homeostasis and various pathophysiological processes. As a member of the evolutionarily conserved thrombospondin family, THBS4 is a multidomain adhesive glycoprotein characterized by six distinct structural domains that mediate its diverse biological functions. Through dynamic interactions with various ECM components, THBS4 plays pivotal roles in cell adhesion, proliferation, inflammation regulation, and tissue remodeling, establishing it as a key modulator of microenvironmental organization. The transcription and translation of THBS4 gene, as well as the activity of the THBS4 protein, are tightly regulated by multiple signaling pathways and extracellular cues. Positive regulators of THBS4 include transforming growth factor-β (TGF-β), interferon-γ (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), bone morphogenetic proteins (BMP12/13), and other regulatory factors (such as B4GALNT1, ITGA2/ITGB1, PDGFRβ, etc.), which upregulate THBS4 at the mRNA and/or protein level. Conversely, oxidized low-density lipoprotein (OXLDL) acts as a potent negative regulator of THBS4. This intricate regulatory network ensures precise spatial and temporal control of THBS4 expression in response to diverse physiological and pathological stimuli. Functionally, THBS4 acts as a critical signaling hub, influencing multiple downstream pathways essential for cellular behavior and tissue homeostasis. The best-characterized pathways include: (1) the PI3K/AKT/mTOR axis, which THBS4 modulates through both direct and indirect interactions with integrins and growth factor receptors; (2) Wnt/β-catenin signaling, where THBS4 functions as either an activator or inhibitor depending on the cellular context; (3) the suppression of DBET/TRIM69, contributing to its diverse regulatory roles. These signaling connections position THBS4 as a master regulator of cellular responses to microenvironmental changes. Substantial evidence links aberrant THBS4 expression to a range of pathological conditions, including neoplastic diseases, cardiovascular disorders, fibrotic conditions, neurodegenerative diseases, musculoskeletal disorders, and atopic dermatitis. In cancer biology, THBS4 exhibits context-dependent roles, functioning either as a tumor suppressor or promoter depending on the tumor type and microenvironment. In the cardiovascular system, THBS4 contributes to both adaptive remodeling and maladaptive fibrotic responses. Its involvement in fibrotic diseases arises from its ability to regulate ECM deposition and turnover. The diagnostic and therapeutic potential of THBS4 is particularly promising in oncology and cardiovascular medicine. As a biomarker, THBS4 expression patterns correlate significantly with disease progression and patient outcomes. Therapeutically, targeting THBS4-mediated pathways offers novel opportunities for precision medicine approaches, including anti-fibrotic therapies, modulation of the tumor microenvironment, and enhancement of tissue repair. This comprehensive review systematically explores three key aspects of THBS4 research(1) the fundamental biological functions of THBS4 in ECM organization; (2) its mechanistic involvement in various disease pathologies; (3) its emerging potential as both a diagnostic biomarker and therapeutic target. By integrating recent insights from molecular studies, animal models, and clinical investigations, this review provides a framework for understanding the multifaceted roles of THBS4 in health and disease. The synthesis of current knowledge highlights critical research gaps and future directions for exploring THBS4-targeted interventions across multiple disease contexts. Given its unique position at the intersection of ECM biology and cellular signaling, THBS4 represents a promising frontier for the development of novel diagnostic tools and therapeutic strategies in precision medicine.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Objective To compare the clinical curative effect of retroauricular and tympanic injection of methylprednisolone sodium succinate combined with hyperbaric oxygen in nerve deafness.Methods A retrospective analysis was performed on the case data with nerve deafness.According to cohort method,they were divided into retroauricular injection group(retroauricular injection of 40 mg methylprednisolone sodium succinate+hyperbaric oxygen therapy)and tympanic injection group(tympanic injection of 40 mg methylprednisolone sodium succinate+hyperbaric oxygen therapy).Both groups were treated for 7 times(once every other day).The curative effect,pure tone hearing threshold,oxidative stress and inflammatory response indexes were compared between the two groups,and adverse reactions were statistically analyzed.Results There were 56 cases in retroauricular injection group and 60 cases in tympanic injection group.There was no significant difference in total response rate between retroauricular injection group and tympanic injection group(92.86％vs 88.33％,P＞0.05).After treatment,average pure tone hearing thresholds in retroauricular injection group and tympanic injection group were(38.49±5.71)and(40.35±6.23)dB;high-frequency hearing thresholds were(61.36±6.52)and(63.42±7.09)dB;low-frequency hearing thresholds were(59.72±6.85)and(60.81±7.26)dB;levels of superoxide dismutase(SOD)were(112.38±10.72)and(110.43±10.29)U·mL-1;levels of lipid peroxide(LPO)were(4.69±1.08)and(5.03±1.12)nmol·mL-1;endothelin(ET)levels were(2.11±0.76)and(2.34±0.81)ng·L-1;interleukin-6(IL-6)levels were(31.79±4.27)and(33.18±4.98)pg·mL-1;levels of C-reactive protein(CRP)were(5.25±1.48)and(5.72±1.62)mg·L-1;levels of tumor necrosis factor-α(TNF-α)were(45.33±4.61)and(46.95±5.24)ng·L-;the difference was not statistically significant(all P＞0.05).During treatment,there were significant differences in total incidence of adverse reactions between retroauricular injection group and tympanic injection group(23.21％vs 51.67％,P＜0.05).There were 11 case times of local pain and 4 case times of vertigo in retroauricular injection group,while there were 30 case times of local pain and 15 case times of vertigo in tympanic injection group.Conclusion Retroauricular injection or tympanic injection of methylprednisolone sodium succinate combined with hyperbaric oxygen therapy has the comparable curative effect in patients with nerve deafness;the two administration modes both can promote hearing recovery,relieve reduce oxidative stress and inflammatory response.However,retroauricular injection has lower incidence of local pain and vertigo.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To establish an ultra high performance liquid chromatography-tandem mass spectrometry method for the determination of lacidipine in plasma of beagle dogs was established.Methods It was pretreated by protein precipitation method and the internal standard was nimodipine.Chromatographic column:ACQUITYUPLC? BEH C8(2.1 mm x50.0 mm,1.7 μm),mobile phase:100％water containing 5 mmol·L-1 ammonium acetate-100％acetonitrile,flow rate:0.7 mL·min-1,column temperature:40 ℃,automatic injector temperature:4 ℃,injection volume:20 μL.Electrospray ionization source,positive ion mode,multi-reaction monitoring.The specificity,residual effect,standard curve and quantitative lower limit,precision and recovery,matrix effect and stability of the method were investigated.Results Lacidipine has a good linear relationship in the range of 0.10-50.0 ng·mL-1,r=0.996 6,the lower limit of quantification was 0.10 ng·mL-1.The specificity was good.The intra-and inter-relative standard deviation was less than 12％.The extraction recovery was higher than 80％,and the stability was good.Conclusion The method has the advantages of high sensitivity,simple operation and short analysis time,and was suitable for the pharmacokinetic study of lacidipine in Beagle dog plasma.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Polygoni multiflori radix praeparata is a processed product of Polygoni multiflori radix(Polygonum multiflorum Thunb.),and its main components include stilbene glycosides,anthraquinones,flavonoids,alkaloids,phenolic acids,etc.It has antioxidant,antianemic,anti-tumor,hypoglycemic,anti-inflammatory effects,etc,and is widely used in clinical practice.The processing technology is mainly stewinging with black bean juice,steaming,processing for 9 times and braising and simmering.After processing,the color deepens and the content of composition changes.By consulting domestic and foreign literature,the research on Polygoni multiflori radix praeparata is not comprehensive enough compared with Polygoni multiflori radix.Therefore,this paper mainly summarizes the processing technology,chemical composition and pharmacological activity of Polygoni multiflori radix preparata reported in the past 20 years,and provides a reference for further development of Polygoni multiflori radix preparata.

Objective To investigate the effects of calorie-restricted diet(CRD)combined with intesti-nal micro-ecological preparation on the clinical outcomes of overweight/obese infertile patients undergoing fresh embryo transfer cycle.Methods A total of 197 cases of fresh embryo transfer assisted by in vitro fertili-zation(IVF)/intracytoplasmic sperm injection(ICSI)-embryo transfer(ET)in the hospital from January,2019 to December,2021 were selected as the research objects,and were divided into the overweight interven-tion group(n=46),the overweight control group(n=85)and the obesity intervention group(n=85)accord-ing to the body mass index(BMI)and whether they accepted CRD intervention or not.Results Compared to before the intervention,the overweight intervention group had significantly lower body mass[(63.59±4.90)kg vs.(67.47±5.10)kg],BMI[(25.74±1.26)kg/m2 vs.(26.58±0.75)kg/m2],body fat percentage[(36.51±3.76)％vs.(39.21±4.26)％],waist to hip ratio(0.88±0.04 vs.0.91±0.04),visceral fat grade(10.80±2.45 vs.12.63±2.60),and basal metabolic rate[(1 235.98±74.32)kcal vs.(1 254.63±77.23)kcal],P＜0.05;The body mass[(71.79±9.78)kg vs.(77.18±9.62)kg],BMI[(29.04±2.96)kg/m2 vs.(31.21±2.64)kg/m2],body fat percentage[(40.47±4.77)％vs.(43.97±3.81)％],waist to hip ratio(0.92±0.05 vs.0.96±0.06),and visceral fat grade(14.00±3.74 vs.16.59±3.15)of the obesity interven-tion group were significantly reduced(P＜0.05).Compared with the overweight control group,the number of transplanted embryos(1.85±0.36 vs.1.96±0.19)in the overweight intervention group was less(P＜0.05),while the number of live births(0.61±0.37 vs.0.56±0.36)was more,the live birth rate(43.48％vs.40.00％)was higher,but there was no statistically significant difference(P＞0.05).The clinical preg-nancy rate and live birth rate in the obesity intervention group were higher than those in the control group(72.41％vs.51.35％and 58.62％vs.35.14％),with no statistical significance,but with a strong statistical significance(P＞0.05).Conclusion CRD combined with intestinal micro-ecological preparation can signifi-cantly reduce the body mass and body fat of overweight/obese infertile patients,may help improve the success rate of assisted reproduction in obese infertile patients.