Objective : To investigate the diagnostic value of plasma calprotectin in childern with refractory mycoplasma pneumoniae pneumonia(RMPP). Methods : A multicenter, prospective cohort study was conducted, enrolling 228 children with mycoplasma pneumoniae pneumonia(MPP). Among these, 177 cases were diagnosed with general mycoplasma pneumoniae pneumonia(GMPP), while the remaining 51 cases were RMPP. Plasma was collected at the time of admission of the children in both groups, and calprotectin levels were measured. A one-way difference analysis was performed on the blood test indexes of the children in the two groups, and the difference variables withP<0.05 between the two groups were included in a multifactorial logistic regression to analyze the risk factors for the progression of GMPP to RMPP. The differential diagnostic value of plasma calprotectin for GMPP and RMPP was analyzed by the receiver operating characteristic(ROC) curves. Results : Univariate analysis showed that plasma calprotectin levels were significantly higher in the RMPP group than those in the GMPP group, and the difference was statistically significant(P<0.05). Logistic regression analysis showed that plasma calprotectin was an independent risk factor for RMPP(OR=1.323,P<0.001), ROC curve analysis showed that plasma calprotectin had a higher diagnostic value for the differential diagnosis of GMPP and RMPP(AUC =0.839), and its combination with C-reactive protein and albumin could significantly improve the diagnostic efficiency. Conclusion Plasma calprotectin has good clinical value for the diagnosis of RMPP.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.

Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Objective:To analyze pancreatic cancer incidence and mortality data in China and worldwide and to provide data for pancreatic cancer prevention and control efforts.Methods:Data of pancreatic cancer incidence and mortality rates, along with historical and predictive data, were obtained from the GLOBOCAN 2022 database. Epidemiological characteristics of pancreatic cancer was analyzed by region, sex, age and Human Development Index (HDI). Spearman's correlation coefficient test was used to assess the relationship between HDI and age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR).Results:In 2022, the global number of new cases and deaths of pancreatic cancer will be 511 thousand and 467 thousand, respectively, with an ASIR and ASMR of 4.7/10 5 and 4.2/10 5, respectively. North America and Europe had the highest pancreatic cancer incidence and mortality rates of 8.5/10 5 and 7.3/10 5, respectively. Global ASIR and ASMR in men were both 1.4 times higher than those in women. HDI levels were positively correlated with ASIR ( r=0.79, P＜0.001) and ASMR ( r=0.78, P＜0.001) of pancreatic cancer in all regions. The number of pancreatic cancer cases and deaths in China were 119 thousand and 106 thousand, respectively, while the ASIR and ASMR of pancreatic cancer were 4.4/10 5 and 3.9/10 5, respectively. Both ASIR and ASMR in men were both 1.5 times higher than those in women in China. The number of pancreatic cancer incidence and death cases in China in 2050 is predicted to be 216 thousand and 204 thousand cases, with an increase of 81.5% and 92.5% compared with 2022, respectively. Conclusions:The disease burden of pancreatic cancer varies significantly among different regions, genders and ages. Pancreatic cancer incidence and mortality are positively correlated with HDI. The incidence and mortality rates of pancreatic cancer in China are close to the global average, but the number of new cases and deaths is high. Prevention and control should be strengthened to improve the survival of pancreatic cancer patients.

Objective To investigate the multi-target mechanisms of quercetin in treating endometriosis(EMT)through integrative network pharmacology analysis.Methods Active targets of quercetin were collected from the TCMSP database,while EMT-related differentially expressed genes(DEGs)were identified through the Gene Expression Omnibus(GEO)dataset.A comparative analysis was conducted to pinpoint potential therapeutic targets of quercetin for EMT treatment.Functional enrichment analyses were employed to investigate the biological functions associated with these targets,and a protein-protein interaction(PPI)network was conducted to identify core targets.Molecular docking and dynamics simulations were performed to validate the binding characteristics between quercetin and the core targets.The top 2 target protein pairs,HSP90AB1 and AR,exhibiting the lowest binding energy,were selected for subsequent cellular experimental validation.Human EMT-immortalized ectopic endometrial epithelial cell line 12Z(n=6,independent replicates)was subjected,and CCK-8 assay was used to determine ehe effects of quercetin on cell viability and proliferation,and the half-maximal inhibitory concentration(IC50)was calculated at 48 h after treatment.Then the 12Z cells were treated with quercetin at a concentration gradient of 0,30,60 and 90 μmol/L,the migration and invasion abilities were assessed with cell scratch and cell invasion assays.Western blotting was conducted to detect the changes in the expression of HSP90AB1 and AR proteins after different doses of treatment.Results There were 49 potential EMT-related therapeutic targets and 10 core targets identified.Functional enrichment analyses revealed that these targets were significant enriched in inflammation-related signaling pathways,including AGE-RAGE,ErbB and TNF;immune-related pathways,such as Th17 cell differentiation,T/B cell receptor signaling;angiogenesis-related pathways like VEGF;and hormonal regulatory pathways involving estrogen and GnRH.Molecular docking demonstrated that quercetin exhibited favorable binding activity(binding energy<-5 kcal/mol)with all core target proteins,with particularly strong binding energies(<-7 kcal/mol)observed for AR,EGFR,FOS,ERBB2,and HSP90AB1.Molecular dynamics simulations revealed that quercetin forms sustained hydrogen bond interactions with AR and HSP90AB1,facilitating the formation of stable complexes.CCK-8 assay,cell scratch assay,and transwell invasion assay indicated that quercetin inhibited the proliferative activity,and migrative and invasive abilities of 12Z cells in a concentration-dependent manner,with more pronounced inhibitory effects observed at 60 and 90 μmol/L quercetin(P<0.001);Western blotting revealed that treatment of 12Z cells with varying quercetin concentrations for 48 h up-regulated the expression of HSP90AB1 and AR,with the most significant increase observed at 90 μmol/L quercetin(HSP90AB1,P<0.05;AR,P<0.001).The restored expression levels of HSP90AB1 and AR showed positive correlations with the proliferative activity,migrative and invasive abilities of ectopic endometrial cells.Conclusion Quercetin effectively addresses endometriosis through multiple molecular targets and signaling pathways,and stabilization of the HSP90AB1/AR complex and subsequent protein upregulation represents a key therapeutic mechanism.

Objective:To analyze pancreatic cancer incidence and mortality data in China and worldwide and to provide data for pancreatic cancer prevention and control efforts.Methods:Data of pancreatic cancer incidence and mortality rates, along with historical and predictive data, were obtained from the GLOBOCAN 2022 database. Epidemiological characteristics of pancreatic cancer was analyzed by region, sex, age and Human Development Index (HDI). Spearman's correlation coefficient test was used to assess the relationship between HDI and age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR).Results:In 2022, the global number of new cases and deaths of pancreatic cancer will be 511 thousand and 467 thousand, respectively, with an ASIR and ASMR of 4.7/10 5 and 4.2/10 5, respectively. North America and Europe had the highest pancreatic cancer incidence and mortality rates of 8.5/10 5 and 7.3/10 5, respectively. Global ASIR and ASMR in men were both 1.4 times higher than those in women. HDI levels were positively correlated with ASIR ( r=0.79, P＜0.001) and ASMR ( r=0.78, P＜0.001) of pancreatic cancer in all regions. The number of pancreatic cancer cases and deaths in China were 119 thousand and 106 thousand, respectively, while the ASIR and ASMR of pancreatic cancer were 4.4/10 5 and 3.9/10 5, respectively. Both ASIR and ASMR in men were both 1.5 times higher than those in women in China. The number of pancreatic cancer incidence and death cases in China in 2050 is predicted to be 216 thousand and 204 thousand cases, with an increase of 81.5% and 92.5% compared with 2022, respectively. Conclusions:The disease burden of pancreatic cancer varies significantly among different regions, genders and ages. Pancreatic cancer incidence and mortality are positively correlated with HDI. The incidence and mortality rates of pancreatic cancer in China are close to the global average, but the number of new cases and deaths is high. Prevention and control should be strengthened to improve the survival of pancreatic cancer patients.

Objective:To investigate the etiology of hand, foot and mouth disease (HFMD) in Mianyang city in 2022, and to analyze the genetic characteristics of coxsackievirus A6.Methods:Pharyngeal swabs were collected from patients with HFMD in Mianyang city in 2022. Real-time fluorescence quantitative PCR was used to detect enteroviruses in the samples. Part of the VP1 gene in enterovirus-positive samples was amplified by nested PCR using enterovirus typing primers to further identify the viral types. The VP1 coding region of all CVA6-positive samples and the whole genome of some samples were amplified and sequenced by PCR. The endemic strain in Mianyang city was analyzed for phylogeny, gene homology, amino acid variation and genetic recombination.Results:A total of 151 pharyngeal swabs were collected, and 104 enterovirus-positive samples were detected by real-time fluorescence quantitative PCR, with an overall detection rate of 68.88% (104/151). The typing results showed that there were 77 cases of CVA6 infection, with a positive rate of 50.99% (77/151). The full-length VP1 genes of 77 CVA6 strains were amplified, sequenced, and successfully spliced, and phylogenetic analysis showed that all 77 strains were of the D3 genotype. There were multiple amino acid variant sites in the prevalent strains in Mianyang city compared with the reference strain. Twenty whole genome sequences were amplified, sequenced, and successfully spliced, and homology analysis showed that the nucleotide homology between the 20 positive sequences ranged from 97.0% to 99.9%. Phylogenetic tree and recombination analysis showed that no recombination occurred in the coding regions of the epidemic strains in this study.Conclusions:The predominant pathogen causing HFMD in Mianyang city in 2022 is CVA6 D3 subtype, which is consistent with the national epidemic in 2022.

Objective:To understand the prevalence and characteristics of Rhinovirus (HRV) infection in influenza-like Illness (ILIs) patients in Mianyang, Sichuan province, China.Methods:Throat swabs were collected from patients of ILIs in sentinel hospitals in Mianyang during 2021—2022. Real-time fluorescence quantitative PCR was used to detect 16 common pathogens. The VP4/VP2 coding region genes of HRV positive samples were amplified by nest PCR. The phylogeny, consistency and amino acid variation of different serotypes were analyzed and compared with reference sequences from GenBank database.Results:A total of 332 ILIs′ samples were collected with a virus detection rate of 58.73% (195/332) in Mianyang. Among them, 23 samples (23/332) were HRV-positive, and 18 VP4/VP2 sequences of HRV strains were successfully amplified. It was found that 13 HRV serotypes were detected in ILIs samples in Mianyang, which belonged to three genotypes, namely HRV-A (12 strains), HRV-B (5 strains) and HRV-C (1 strain).Conclusions:HRV was one of the pathogens of ILIs cases in Mianyang during 2021—2022, with HRV-A types as the dominant strains.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.