ObjectiveQi deficiency and phlegm dampness syndrome is a common type of clinical traditional Chinese medicine（TCM） syndrome. However， there is no standard， scientific， and accurate report on the construction of animal models of Qi deficiency and phlegm dampness syndrome. This study aims to construct a mouse model of Qi deficiency and phlegm dampness syndrome by using a multi-factor composite modeling method and to evaluate the model. MethodsTwenty-one C57BL/6 mice were randomly divided into three groups with seven mice in each group， which were the normal group， model group， and Shenling Baizhusan （SLBZ） group. The control group was fed with ordinary diet and kept in a normal environment. The model group and SLBZ group were fed with a high-fat diet in a high-humidity environment. Swimming with heavy weights until exhaustion and gavage with cold water or lard were used to establish the mouse model of Qi deficiency and phlegm dampness syndrome. In order to test the syndrome by prescription， mice in the SLBZ group were treated with SLBZ for 14 days after model construction. The exhaustive swimming time， body weight， serum lipid levels， tongue changes， "Qi deficiency and phlegm dampness" assessment scale score， and cecal index of mice in each group were measured. The feces of each group of mice were sent for metagenomics and metabolome sequencing， and the changes in intestinal flora and metabolites were analyzed. ResultsAfter the modeling of Qi deficiency and phlegm dampness syndrome， the exhaustive swimming time of mice was obviously shortened （P<0.01）. The serum total cholesterol， low density lipoprotein cholesterol， and non-high density lipoprotein cholesterol of mice were significantly increased （all P<0.01）. The tongue of mice was significantly different from that of the normal group， and the score of the assessment scale was significantly higher than that of the control group （P<0.01）. Cecal index decreased significantly （P<0.01）. The serum lipid level， tongue image， assessment scale score， and cecal index were reversed in the SLBZ group. Metagenomic and metabolome sequencing results showed that intestinal flora and fecal metabolites were significantly changed in mice with Qi deficiency and phlegm dampness syndrome. Akkermansia_muciniphila， Faecalibaculum_rodentium， Eubacterium_plexicaudatum， Eubacterium sp 14_2， Candida glabrata， Romboutsia_ilealis， Turicibacter sp TS3， and other bacteria had significant changes， and the expressions of intestinal metabolites such as chenodeoxycholic acid， choline， L-phenylalanine betaine， and 2-phenylbutyric acid were significantly changed. Related metabolic pathways such as linoleic acid metabolism， primary bile acid biosynthesis， lysine degradation， arginine biosynthesis， and alpha-linolenic acid metabolism were affected. ConclusionThe Qi deficiency and phlegm dampness model of mice can be constructed by the multi-factor composite modeling method of high-fat diet feeding， high-humidity environment feeding， exhaustive swimming with heavy weight， and intragastric administration with cold water or lard. The blood lipid level， tongue change， score of "Qi deficiency and phlegm dampness assessment scale"， cecal index， and changes in related intestinal flora and metabolites of mice can be used as key indicators for model evaluation.

ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 （Ptpn2） on the inflammatory response of mouse alveolar macrophages （MH-S） induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups： the negative control group with an empty vector （NC）， the overexpressed Ptpn2 group （P）， the negative control group with an empty vector + SiO₂ induction （NS）， and the overexpressed Ptpn2 + SiO₂ induction group （PS）. Isobaric tags for relative and absolute quantification （iTRAQ） combined with liquid chromatography-tandem mass spectrometry （LC-MS/MS） were used to screen differential proteins， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor （TNF） α， Gasdermin D （GSDMD）， and Transforming growth factor （TGF）-β1. Western blot was used to detect the protein expression levels of PTPN2， Toll-like receptor 4 （TLR4）， tumor necrosis factor-α （TNF-α）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes （BP）， these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB （NF-κB） signaling， cell activation and signal transduction involved in immune responses， and regulation of receptor signaling pathways by signal transducer and activator of transcription （STAT）， etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway， NF-κB signaling pathway， NOD-like receptor signaling pathway， TGF-β signaling pathway， and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group， the expressions of TNF α， GSDMD， and TGF-β1 in the cells of the NS group increased （P < 0.05）； compared to the NS group， the expression of the aforementioned proteins in the PS group decreased in cellular proteins（P < 0.05）. The results of Western blot showed that compared with the NC group， the protein expression levels of PTPN2， p-NF-κB，MyD88，TLR4，NLRP3，GSDMD，Caspase-1，IL-1β， TGF-βR1， TGF-βR，p-Smad2/3 in the NS group were significantly upregulated （P < 0.05）； compared with the NS group， the expression levels of the aforementioned proteins in the PS group were significantly downregulated （P < 0.05）. ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling， NLRP3 signaling， and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

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.

Objective The aim of this study is to discuss the causal relationship between periodontal disease(PD)and prostate cancer(PCa).Methods A two-sample bidirectional Mendelian randomization(MR)analysis based on publicly statistical data from genome-wide association studies(GWAS)was conducted.MR Egger,weighted medium,simple mode and weighted mode were supplemented,while inverse variance weighted analysis(IVW)was the main method of analysis.Heterogeneity testing,pleiotropy testing and leave-one-out testing were used to assess the sensitivity and stabili-ty.Results The results of MR analysis showed that PD had no significant impact on the occurrence of PCa:East Asian(IVW,PD:OR=1.07,P=0.48);European(IVW,PD:OR=1.00,P=0.37,periodontitis:OR=1.03,P=0.14,chronic gingivitis:OR=0.99,P=0.37,chronic periodontitis:OR=1.03,P=0.22).The reverse MR analysis also did not show a causal relationship between PCa and PD:East Asian(IVW,PD:OR=0.97,P=0.22);European(IVW,PD:OR=0.84,P=0.44,periodontitis:OR=1.01,P=0.75,chronic gingivitis:OR=0.93,P=0.23,chronic periodontitis:OR=0.99,P=0.80).The results of other analysis were consistent with those of IVW analysis.Conclusions The results of our two-sample bidirectional MR analysis do not support a causal relationship between PD and PCa.

Objectiv To investigate an autosomal dominant non-syndromic hearing loss family pedigree com-prehensively,aiming to precisely define its clinical phenotypes and uncover the underlying molecular genetic etiolo-gy.Methods A detailed interrogation of the proband's medical history and family history was conducted.Physical examinations,audiological assessments and temporal bone CT scans were performed.Genomic DNA was extracted from the peripheral blood of the proband(Ⅳ-8)for whole-exome sequencing(WES).Subsequently,candidate vari-ants identified through WES were validated among family members using Sanger sequencing.Results There were 36 individuals in 4 generations in this family pedigree,showing autosomal dominant inheritance.Among them,16 individuals presented with progressive hearing loss.Audiological examinations were completed for 13 of them,re-vealing normal hearing in three individuals(Ⅲ-1,Ⅲ-1 1,Ⅳ-4)and bilateral symmetric hearing loss of varying se-verity in the remaining ten(Ⅱ-2,Ⅱ-4,Ⅱ-10,Ⅲ-4,Ⅲ-10,Ⅲ-13,Ⅲ-14,Ⅳ-1,Ⅳ-7,Ⅳ-8),and the degree of hearing loss was related to age.WES of Ⅳ-8 revealed that she carried the variant NM_199330.2(HOMER2):c.1064 A＞G(p.Ter354Trpext10),and Sanger sequencing verified the variation at this site.Peripheral blood samples of 18 individuals in this family were collected in total.All affected individuals(Ⅱ-2,Ⅱ-4,Ⅱ-10,Ⅲ-4,Ⅲ-9,Ⅲ-10,Ⅲ-13,Ⅲ-14,Ⅳ-1,Ⅳ-7,Ⅳ-8)carried the HOMER2 c.1064 A＞G variant,except for one young member(Ⅳ-6)who had not yet developed hearing loss.Unaffected individuals(Ⅱ-5,Ⅲ-1,Ⅲ-5,Ⅲ-11,Ⅳ-2,Ⅳ-4)lacked the variant,demonstrating complete cosegregation of genotype and phenotype.According to ACMG guide-lines,this variant was classified as likely pathogenic(PM2+PP1+PM4).Conclusion The c.1064 A＞G(p.Ter354Trpext10)variant of the HOMER2 gene is the molecular genetic etiology of this hereditary deafness family pedigree.

Early cervical cancer can be cured through surgery,but about half of patients are already locally advanced at the time of initial diagnosis.Cisplatin-based concurrent chemoradiotherapy is the standard treatment for locally advanced cervical cancer.However,the prognosis of these patients remains poor after completing simultaneous radiotherapy and chemotherapy.The emergence of immunotherapy has dramatically improved the prognosis of patients with advanced and recurrent cervical cancer,and is gradually being combined with conventional treatments such as chemotherapy,radiotherapy and targeted therapy.Recent studies have shown that the combination of pembrolizumab and concurrent radiotherapy significantly improves the progression-free survival rate of patients with lo-cally advanced cervical cancer,without significantly increasing the incidence of toxic side effects;The combination of neoadjuvant chemotherapy with immune checkpoint inhibitors and surgery is expected to become a new treatment option for locally advanced cervi-cal cancer;The use of nabumolizumab immunomaintenance therapy after synchronous radiotherapy and chemotherapy may improve the survival rate and treatment efficacy of patients with locally advanced cervical cancer.This article provides a review of the progress in immunotherapy for locally advanced cervical cancer.

Objectiv To investigate an autosomal dominant non-syndromic hearing loss family pedigree com-prehensively,aiming to precisely define its clinical phenotypes and uncover the underlying molecular genetic etiolo-gy.Methods A detailed interrogation of the proband's medical history and family history was conducted.Physical examinations,audiological assessments and temporal bone CT scans were performed.Genomic DNA was extracted from the peripheral blood of the proband(Ⅳ-8)for whole-exome sequencing(WES).Subsequently,candidate vari-ants identified through WES were validated among family members using Sanger sequencing.Results There were 36 individuals in 4 generations in this family pedigree,showing autosomal dominant inheritance.Among them,16 individuals presented with progressive hearing loss.Audiological examinations were completed for 13 of them,re-vealing normal hearing in three individuals(Ⅲ-1,Ⅲ-1 1,Ⅳ-4)and bilateral symmetric hearing loss of varying se-verity in the remaining ten(Ⅱ-2,Ⅱ-4,Ⅱ-10,Ⅲ-4,Ⅲ-10,Ⅲ-13,Ⅲ-14,Ⅳ-1,Ⅳ-7,Ⅳ-8),and the degree of hearing loss was related to age.WES of Ⅳ-8 revealed that she carried the variant NM_199330.2(HOMER2):c.1064 A＞G(p.Ter354Trpext10),and Sanger sequencing verified the variation at this site.Peripheral blood samples of 18 individuals in this family were collected in total.All affected individuals(Ⅱ-2,Ⅱ-4,Ⅱ-10,Ⅲ-4,Ⅲ-9,Ⅲ-10,Ⅲ-13,Ⅲ-14,Ⅳ-1,Ⅳ-7,Ⅳ-8)carried the HOMER2 c.1064 A＞G variant,except for one young member(Ⅳ-6)who had not yet developed hearing loss.Unaffected individuals(Ⅱ-5,Ⅲ-1,Ⅲ-5,Ⅲ-11,Ⅳ-2,Ⅳ-4)lacked the variant,demonstrating complete cosegregation of genotype and phenotype.According to ACMG guide-lines,this variant was classified as likely pathogenic(PM2+PP1+PM4).Conclusion The c.1064 A＞G(p.Ter354Trpext10)variant of the HOMER2 gene is the molecular genetic etiology of this hereditary deafness family pedigree.

Early cervical cancer can be cured through surgery,but about half of patients are already locally advanced at the time of initial diagnosis.Cisplatin-based concurrent chemoradiotherapy is the standard treatment for locally advanced cervical cancer.However,the prognosis of these patients remains poor after completing simultaneous radiotherapy and chemotherapy.The emergence of immunotherapy has dramatically improved the prognosis of patients with advanced and recurrent cervical cancer,and is gradually being combined with conventional treatments such as chemotherapy,radiotherapy and targeted therapy.Recent studies have shown that the combination of pembrolizumab and concurrent radiotherapy significantly improves the progression-free survival rate of patients with lo-cally advanced cervical cancer,without significantly increasing the incidence of toxic side effects;The combination of neoadjuvant chemotherapy with immune checkpoint inhibitors and surgery is expected to become a new treatment option for locally advanced cervi-cal cancer;The use of nabumolizumab immunomaintenance therapy after synchronous radiotherapy and chemotherapy may improve the survival rate and treatment efficacy of patients with locally advanced cervical cancer.This article provides a review of the progress in immunotherapy for locally advanced cervical cancer.

Objective The aim of this study is to discuss the causal relationship between periodontal disease(PD)and prostate cancer(PCa).Methods A two-sample bidirectional Mendelian randomization(MR)analysis based on publicly statistical data from genome-wide association studies(GWAS)was conducted.MR Egger,weighted medium,simple mode and weighted mode were supplemented,while inverse variance weighted analysis(IVW)was the main method of analysis.Heterogeneity testing,pleiotropy testing and leave-one-out testing were used to assess the sensitivity and stabili-ty.Results The results of MR analysis showed that PD had no significant impact on the occurrence of PCa:East Asian(IVW,PD:OR=1.07,P=0.48);European(IVW,PD:OR=1.00,P=0.37,periodontitis:OR=1.03,P=0.14,chronic gingivitis:OR=0.99,P=0.37,chronic periodontitis:OR=1.03,P=0.22).The reverse MR analysis also did not show a causal relationship between PCa and PD:East Asian(IVW,PD:OR=0.97,P=0.22);European(IVW,PD:OR=0.84,P=0.44,periodontitis:OR=1.01,P=0.75,chronic gingivitis:OR=0.93,P=0.23,chronic periodontitis:OR=0.99,P=0.80).The results of other analysis were consistent with those of IVW analysis.Conclusions The results of our two-sample bidirectional MR analysis do not support a causal relationship between PD and PCa.