ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63^-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63^-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

Objective To perform laboratory detection and molecular traceability analysis on a case of imported kala-azar in Shenzhen to determine the infection strain. Methods Bone marrow puncture fluid and blood samples from a case of kala-azar in Shenzhen were collected for laboratory tests. The patient's bone marrow puncture fluid smears were stained with Giemsa and examined under a microscope. Blood samples were examined for antibodies using the rk39 visceral leishmania rapid diagnostic reagent. Whole blood DNA was extracted, and the ITS-1 sequence was amplified by PCR, sequenced and aligned, and a phylogenetic tree was constructed based on the ITS-1 sequence. Results Microscopic examination of the patient's bone marrow smears revealed a large number of Leishmania amastigotes without flagella, confirming the diagnosis of kala-azar. The patient's blood was tested positive with the rk39 rapid diagnostic reagent, and PCR amplification yielded an ITS-1 gene product sequence that matched the expected size. Sequence alignment with the NCBI database showed 100% sequence similarity with the ITS-1 gene sequence of Leishmania infantum, confirming the infecting strain as Leishmania infantum. Phylogenetic tree construction of the amplified ITS-1 sequence revealed clustering into a clade with Leishmania infantum , and close to KC347299, one of the reference sequence selected. Conclusions The case of kala-azar in Shenzhen was caused by Leishmania infantum. Kala-azar still occurs in China, so the diagnostic technology of medical personnel in non-epidemic areas should be strengthened so that they can actively use new diagnostic technologies to assist in diagnosis, thus improving their prevention and control ability of Leishmania parasites.

Objective To explore the feasibility of tracing the source of human biological samples by microbiome,and provide new ideas for case investigation.Methods Biological samples from buccal mucosa,foot arch,armpit and other parts of 10 volunteers were collected for three consecutive months.The microbial community structure of the samples was confirmed by using the 16SrRNA gene sequence information.And the microbial community diversity analysis and random forest classification prediction model were carried out.Results There were significant differences in the microbial community structure of the three parts of human body.In this study,a prediction model of random forest classification with an accuracy of more than 90%was successfully constructed.Conclusion In this study,a classification and prediction model based on the microbiome information of human biological samples was constructed to judge the source location,which broadened the forensic application scenarios of human microorganisms.

Glutamine,as the most abundant free amino acid in the human body,plays a crucial role in various physiological processes.These functions include providing energy to cells,supporting immune system function,maintaining intestinal health,and playing a key role in nitrogen transport.Under normal physiological conditions,muscle tissue is the primary site for the synthesis and release of glutamine.After glutamine is released into the bloodstream,it will be transported to the intestines,immune organs or other tissues and play related roles.However,in a state of illness,especially in the presence of tumors,there are significant changes in the metabolism and function of glutamine.The glutamine metabolism can serve as signaling molecules and participates in regulating various signaling pathways within tumor cells,including key pathways that affect cell growth,survival,and metabolism,such as the mTOR and AMPK pathways.This paper reviews the metabolic steps involving glutamine in tumor cells and the role of glutamine blockade in the tumor microenvironment.

Objective:To investigate the protective effect of quercetin(QUE)on acute lung injury(ALI)rats with sepsis.Methods:Sixty male SD rats were randomly divided into 6 groups(n=10):Sham operation group(Sham),model group(CLP),QUE 25 mg/kg group,QUE 50 mg/kg group,QUE 100 mg/kg group and positive drug dexamethasone(DEX)group.Rats in each group were continuously treated for 7 days,and the survival rate was calculated;HE staining and lung wet-to-dry weight ratio(W/D)were used to evaluate the severity of lung injury;TUNEL staining was used to detect lung tissue apoptosis;levels of inflammatory factors,SOD and MDA were detected by the kits;Western blot was used to detect expressions of apoptosis-related proteins and phosphoryla-tion levels of PTEN,β-catenin,protein kinase B(AKT)and glycogen synthase kinase-3β(GSK-3β)in rat lung tissue.Results:Com-pared with CLP group,after QUE 50 mg/kg and 100 mg/kg treatment,survival rate of rats was significantly increased(P<0.05),the degree of inflammatory cell infiltration in lung tissue was reduced,lung injury score and W/D were reduced(P<0.05),apoptosis rate of lung tissue cells and expressions of apoptosis-related proteins were significantly decreased(P<0.05),levels of inflammatory factors were decreased(P<0.05),while the antioxidant capacity was enhanced(P<0.05),phosphorylation levels of PTEN and β-catenin were decreased,while phosphorylation levels of AKT and GSK-3β were increased(P<0.05).Conclusion:QUE protects rats from ALI with sepsis by inhibiting apoptosis,reducing inflammation and antioxidance,which mechanism may be related to PTEN/β-catenin and AKT/GSK-3β pathways.

Epidemiological data and clinical characteristics of patients with tick-borne diseases were analyzed to improve diagnosis and treatment outcomes.The data of 32 patients(epidemiology and clinical characteristics)treated for tick-borne diseases at Beijing Ditan Hospital from January 2013 to June 2023 were retrospectively reviewed.Of the 32 patients,17 were diagnosed with severe fever with thrombocytopenia syndrome(SFTS),5 with Lyme disease,and 10 with rick-ettsial disease.Disease was concentrated from May to Octo-ber each year.There were 14 local cases in Beijing(43.8％),with Pinggu District accounting for the highest proportion(4 cases,28.6％),16 imported cases from other provinces(50.0％),and 2 cases(6.3％)from people living abroad.The median time from disease onset to hospitalization was 8 days and the median length of hospitalization was 10 days.The mean age of patients with tick-borne diseases was 50.16±14.61(range,21-80)years.By occupation,farmers were at the greatest risk of tick-borne diseases(14 cases,43.8％).Erythema migrans(EM)was a typical skin lesion characteristic of Lyme disease,and fever was seen in all three groups,but mainly in patients with SFTS and rickettsial disease,who mainly presented with moderate fever.Decreased WBC and NEUT counts were most commonly seen in SFTS,whereas no WBC ab-normality was seen in patients with Lyme disease.Decreased EOS counts were seen in both SFTS and rickettsial disease,whereas no abnormality was seen in Lyme disease.Decreased PLT counts were typical of SFTS.Patients with rickettsial disease and SFTS showed significant liver damage with markedly elevated ALT and AST levels.Significant myocardial damage with ele-vated CK and CK-MB levels was seen in SFTS.Elevated CRP was mainly seen in rickettsial disease.Elevated PCT counts were mostly seen in rickettsial infections,followed by SFTS.The incidence of tick-borne diseases in Beijing continues to increase an-nually.Since diagnosis is often delayed,vigilant surveillance is key to improve diagnosis.Therefore,detailed epidemiological in-formation of each tick-borne disease based on clinical characteristics is needed to ensure early diagnosis and treatment.