Objective　To analyze the epidemiological characteristics and infection sources of six human Streptococcus suis infection outbreaks in Shenzhen in 2023, and to provide a reference for effective prevention and control of the epidemic. Methods　Field epidemiological methods were used to investigate the disease onset and medical consultation process, exposure history of household and farmer market pork stalls, and other relevant factors. Data on patient demographics, clinical profiles, epidemiological characteristics, and common exposure cases were collected. Blood, cerebrospinal fluid, and environmental samples were collected for pathogen detection and genotyping. Spatial-geographical analysis of infection characteristics was performed using the professional mapping software ArcMap. Results　In 2023, a total of six cases were reported in Shenzhen, all of which were severe hospitalized cases with no deaths. Among them, five cases were of the meningitis type, and one was of the common type. All patients improved and were discharged after treatment. All six cases were male, with a median age of 47.5 years, and all had a history of direct exposure to raw pork through hand-skin wounds. Two cases were engaged in raw pork sales, while four were non-occupationally exposed individuals. Of the six cases, four were identified as Streptococcus suis serotype 2, and two were serotype 14. The positive rate of raw pork and environmental samples was 8.45% (6/71). Field epidemiological investigation found these six outbreaks were mainly directed toward three slaughterhouses in Guangming District, Bao'an District, and Longgang District. However, different genetic typing results suggested sporadic cases. Conclusions　These six outbreaks in Shenzhen in 2023 were all sporadic individual cases, showing characteristics such as multiple-point sporadic occurrences, diversified case composition, and primarily meningitis-type clinical manifestations. Although the genetic typing of the samples varied, the epidemiological investigation indicated three slaughterhouses as potential sources, providing a scientific basis for source control. In infectious disease epidemic source tracing, gene sequencing combined with field epidemiological surveys is more conducive to determining the source of infection and the relationship between transmission.

To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective To explore the effect of saururus chinensis tannin on proliferation and mi-gration of non-small cell lung cancer(NSCLC)cells by regulating Hippo/YAP signaling pathway.Methods Human NSCLC cell line A549 was treated with different concentrations of saururus chinen-sis tannin.Cell viability was detected by CCK-8 assay to screen appropriate drug concentrations.NSCLC cells were randomly divided into control group,low-concentration saururus chinensis tannin group,medium-concentration saururus chinensis tannin group,high-concentration saururus chinensis tannin group and high-concentration saururus chinensis tannin+YAP activator(XMU-MP-1)group.Cell viability,colony formation capacity,migration ability and invasion ability were evaluated using the CCK-8 assay,plate colony formation assay,wound healing assay and transwell assay,respective-ly.Expression levels of proteins associated with migration and invasion[E-cadherin,N-cadherin and snail]and proteins related to the Hippo/YAP signaling pathway[Yes-associated protein(YAP),phosphorylated Yes-associated protein(p-YAP),connective tissue growth factor(CTGF)and cys-teine-rich angiogenic inducer 61(CYR61)]were detected by western blot analysis.Results Com-pared with the control group,the cell viability,the number of colony cells,migration and invasion abilities,as well as the expression levels of N-cadherin,snail,YAP,CTGF and CYR61 proteins in the low-concentration saururus chinensis tannin group,medium-concentration saururus chinensis tannin group and high-concentration saururus chinensis tannin group were significantly decreased or reduced,and the expression levels of E-cadherin and p-YAP proteins were significantly increased(P＜0.05),with the most pronounced effects observed in the high-concentration saururus chinensis tannin group.Compared with the high-concentration saururus chinensis tannin group,the cell viabil-ity,the number of colony cells,migration and invasion abilities,as well as the expression levels of N-cadherin,snail,YAP,CTGF and CYR61 in the high-concentration saururus chinensis tannin+YAP activator group were significantly increased or enhanced,while the expression levels of E-cad-herin and p-YAP were significantly decreased(P＜0.05).Conclusion Saururus chinensis tannin may reduce the survival rate of NSCLC cells and inhibit their proliferation,migration and invasion a-bilities by regulating the Hippo/YAP signaling pathway.

Multiple myeloma(MM),a common malignancy of plasma cells,remains an incurable disease de-spite significant therapeutic advancements.A defining characteristic of MM is the recurrent occurrence of cytogenetic ab-normalities,particularly the gains of chromosome 1q21(1q21+),which are among the most frequently observed anoma-lies in this condition,affecting approximately 40%of patients with newly diagnosed MM.While numerous studies have identified 1q21+as an independent prognostic marker linked to poor outcomes in MM,its prognostic significance continues to be debated.An increasing number of national and international prognostic stratification systems classify 1q21+as a high-risk factor;however,its predictive value remains contentious.Variations in 1q21 copy numbers significantly impact genomic instability,drug resistance,and the likelihood of early disease progression,highlighting its growing importance in clinical management strategies.Despite the availability of various therapeutic approaches,such as autologous hemato-poietic stem cell transplantation,immunomodulatory drugs,and proteasome inhibitors,the adverse prognostic implica-tions of 1q21+persist unresolved.This review will explore the latest advancements in understanding the 1q21+in MM,fo-cusing on its pathogenesis,prognostic relevance,and implications for clinical management.

Multiple myeloma(MM),a common malignancy of plasma cells,remains an incurable disease de-spite significant therapeutic advancements.A defining characteristic of MM is the recurrent occurrence of cytogenetic ab-normalities,particularly the gains of chromosome 1q21(1q21+),which are among the most frequently observed anoma-lies in this condition,affecting approximately 40%of patients with newly diagnosed MM.While numerous studies have identified 1q21+as an independent prognostic marker linked to poor outcomes in MM,its prognostic significance continues to be debated.An increasing number of national and international prognostic stratification systems classify 1q21+as a high-risk factor;however,its predictive value remains contentious.Variations in 1q21 copy numbers significantly impact genomic instability,drug resistance,and the likelihood of early disease progression,highlighting its growing importance in clinical management strategies.Despite the availability of various therapeutic approaches,such as autologous hemato-poietic stem cell transplantation,immunomodulatory drugs,and proteasome inhibitors,the adverse prognostic implica-tions of 1q21+persist unresolved.This review will explore the latest advancements in understanding the 1q21+in MM,fo-cusing on its pathogenesis,prognostic relevance,and implications for clinical management.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:Hepatocellular carcinoma(HCC)is the most common primary malignant tumor of the liver.The diagnosis rate of early HCC is low,and most patients are diagnosed at the late stage and have a very poor prognosis.Therefore,it is urgent to explore effective early diagnosis markers and intervention targets for HCC.Cancer/testicular antigen 1A(CTAG1A)is abnormally expressed and highly immunogenic in a variety of tumors,but its expression characteristics and immunogenicity in HCC remain unclear.The aim of this study is to identify the expression and immunogenicity of CTAG1A in HCC tissues and cells,providing a new biomarker for the early diagnosis of HCC and a new potential target for clinical immunotherapy.Methods:This study screened the differentially expressed gene profiles between 10 pairs of very early HCC(BCLC stage 0 HCC)tumors and paracancerous tissues using a transcriptome microarray.The expression of CTAG1A was verified by RT-qPCR in an independent large sample(BCLC stage 0,A,B,C HCC tissues and adjacent non-tumor tissues,n=149)and various hepatocellular carcinoma cell lines.Bioinformatics tools(TepiTool of IEDB database and Swiss Model)were used to predict the MHC-Ⅰ and MHC-Ⅱ epitopes of CTAG1A.The candidate peptides were synthesized by solid-phase polypeptide synthesis method.After purification by HPLC and verification by mass spectrometry assay,the specific T cell responses of peripheral blood mononuclear cells(PBMC)of 9 HCC patients to all peptides were detected by IFN-γ enzyme-linked immunospot assay(ELISpot).The clinical samples were collected from HCC patients admitted to the Third Affiliated Hospital of Naval Medical University(Eastern Hepatobiliary Surgery Hospital)from 2015 to 2022.The collection and usage of all samples were carried out with the consent of the patients,and with the approval of the Ethics Committee of Eastern Hepatobiliary Surgery Hospital(EHBHKY2015-01-017)and in strict accordance with relevant requirements and ethical regulations.Statistical analysis was performed using SPSS 30.0 software,and the diagnostic efficiency was evaluated by ROC curve.Results:Transcriptome chip screening results showed that CTAG1A expression was significantly up-regulated in the very early-stage HCC(BCLC stage 0 HCC)(|FC|=99.16,P<0.0001).The verification using the clinical independent samples showed its high expression in all stages of HCC and better diagnostic efficacy in early-stage HCC(BCLC stage 0 HCC AUC=0.6893,sensitivity=85.71%;BCLC stage A HCC AUC=0.8229,sensitivity=83.33%).Furthermore,the expression of CTAG1A was significantly higher in multiple liver cancer cell lines than in relatively normal liver cell lines(P<0.001).Compared with alpha-fetoprotein(AFP),CTAG1A showed better diagnostic efficacy in BCLC stage 0 and stage A HCC(ROC curve analysis of AFP showed no significant difference in early HCC,P>0.05).Bioinformatics tools predicted that CTAG1A contained 8 MHC-type I and 4 MHC-type II epitopes.The IFN-γ ELISpot assay showed that 12 synthetic peptides could induce PBMC specific T cell response in HCC patients to varying degrees.Conclusion:CTAG1A is significantly overexpressed in early-stage HCC and has multi-epitope immunogenicity,which may activate CD8? and CD4? T cells,suggesting its potential as a target for HCC immunotherapy.It may provide a new direction for developing combined immunotherapy strategies based on mRNA vaccines or adoptive cell therapy.Compared with AFP,CTAG1A exhibits better diagnostic efficacy in early-stage HCC,suggesting its potential as a marker for early diagnosis of HCC.

To summarize the experience of Professor WANG Qingguo in diagnosing and treating wind-cold-dampness arthralgia based on the principle that "the nutrient-defense qi does not merge with wind-cold-dampness qi， so it did not result to arthralgia". By analyzing the relationship between nutrient-defense qi and wind-cold-dampness arthralgia， it is believed that the occurrence of wind-cold-dampness arthralgia is closely related to the movement of nutrient qi and defense qi， and the key to the treatment of this disease is to regulate nutrient qi and defense qi and remove the combination of nutrient-defense qi and wind-cold-dampness qi. The core pathogenesis of wind-cold-dampness arthralgia in the early stage is the initial combination of nutrient-defense qi and wind-cold-dampness qi， and the treatment should harmonize nutrient-defense qi and eliminate the pathogen and release pathogenesis， with Chaihu Guizhi Decoction （柴胡桂枝汤） as the main prescription； the core pathogenesis of the middle stage is nutrient-defense qi and wind-cold-dampness qi cemented together， and the treatment should harmonize and tonify nutrient qi and defense qi and separate the pathogen to alleviate disease， with self-prescribed Chuanteng Tongbi Decoction （穿藤通痹汤） as the main prescription； the core pathogenesis of the late stage is deficiency and stagnation of nutrient-defense qi， wind-cold-dampness qi still exist， and the treatment should tonify and free nutrient qi and defense qi to eliminate pathogen and arthralgia， with self-prescribed Chuanqing Haijia Decoction （穿青海甲汤） plus Duhuo Jisheng Decoction （独活寄生汤） as the main prescription.