BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Fuchs endothelial corneal dystrophy(FECD)is a progressive dystrophic disease characterized by gradual damage to the corneal endothelium, ultimately leading to endothelial decompensation. The current standard treatment, corneal transplantation, has several limitations. Recent studies have shown that Rho-associated kinase(ROCK)inhibitors can promote cell proliferation by modulating the cyclin D and p27 signaling pathways. Additionally, ROCK inhibitors activate Rac1, which drives the actin-related protein complex(ARPC2)to enhance cell adhesion, and regulate processes such as membrane blebbing, nuclear disintegration, and apoptotic body formation, thereby inhibiting the apoptosis of corneal endothelial cells. These findings suggest that ROCK inhibitors may be a promising therapeutic approach for FECD. This review provides an overview of the pharmacological effects, basic research, clinical trials, and potential adverse reactions associated with ROCK inhibitors in the treatment of FECD, with the aim of developing compounds with stable efficacy and minimal side effects for the treatment of FECD in the near future.

Objective:To analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Beijing in 2024, to investigate the infection status of reservoir hosts, vector organisms, and baseline human populations, and provide a scientific basis for formulating prevention and control strategies.Methods:Epidemiological surveys were conducted on all confirmed cases. Serum samples from healthy populations and reservoir hosts were collected for SFTSV antibody detection. Questing ticks were monitored using the flagging method. Real-time fluorescent quantitative PCR was employed to detect SFTSV in cases, reservoir hosts, and ticks. Positive samples underwent whole-genome sequencing and genetic evolution analysis.Results:In 2024, Beijing reported 15 locally infected cases with 4 deaths. The age of onset ranged from 50 to 80 years (median: 66 years). Cases showed a certain degree of geographical clustering, with June being the peak month of onset. The affected population was predominantly farmers, with a male-to-female ratio of 3∶2. Animal contact history emerged as a significant risk factor alongside tick bites. Parthenogenetic tick populations were identified in Pinggu district, while SFTSV-carrying ticks were detected in endemic areas (Mentougou, Shijingshan, and Fengtai Districts). Viral presence was also confirmed in ticks or dogs from non-endemic areas. Sequencing and phylogenetic analysis revealed stable clustering of strains into two distinct genotypes (A and B). Antibody-positive individuals were identified in healthy populations from non-endemic areas.Conclusions:The incidence of SFTS in Beijing is increasing, with natural viral circulation already established in non-endemic regions. Enhanced surveillance and adjusted prevention strategies are urgently needed.

Objective To investigate the efficacy of plantamajoside(PMS)on diabetic peripheral neuropathy(DPN)and to explore its mechanism of action from mitochondrial autophagy.Methods Mice(C57BL/6J)were randomly divided into 6 groups(n=10):normal group(Control),model group(Model),positive drug group(LA),and low(L-PMS),medium(M-PMS),and high(H-PMS)dosage groups.High-sugar and high-fat diet with intraperitoneal injection of streptozotocin was used to duplicate the DPN model.After successful model duplication,the intervention was administered by gavage for 4 weeks.Sciatic nerve was taken,and pathological changes were observed by HE and Nissl staining;oxidative stress indexes SOD,MDA,GSH-Px and inflammatory factors such as IL-1β,IL-6,TNF-αin sciatic nerve tissues were detected by kits,and the expression of VDAC1,TOM20,COX IV,PINK1,Parkin,and autophagy proteins of Beclin1,LC3,P62 in mouse sciatic nerves was detected by Western blotting.Results PMS dose-dependently improved the behavioral indexes of DPN mice,reduced the pathological damage of sciatic nerve,and resulted in tightly arranged sciatic nerve fibers,clearly visible myelin structure,uniform coloration,and increased number of Schwann cells as well as Nissl bodies.Compared with the model group,both the M-PMS group and the H-PMS group increased the expression levels of SOD and GSH-Px(P<0.05),while decreased the expression of MDA(P<0.05);the M-PMS group and the H-PMS groups reduced the expression of IL-1β,IL-6,and TNF-α(P<0.05);the L-PMS group,M-PMS group,and H-PMS group reduced the expression levels of VDAC1,TOM20,and COX IV proteins(P<0.05);the L-PMS group,M-PMS group,and H-PMS group could differentially increase the expression of PINK1,Beclin1,Parkin,and LC3 proteins(P<0.05),and decrease the expression of P62 proteins(P<0.05).Conclusion PMS can play a role in ameliorating neurological injury in DPN mice by promoting PINK1/Parkin pathway-mediated mitochondrial autophagy and alleviating oxidative stress-related inflammatory injury.

During the 14th Five-Year Plan period, the population of China has turned into a stage of negative growth, the fertility rate gradually declined, and the infertility rate gradually increased. The most effective treatment for infertility is assisted reproductive technology (ART), which has brought hope for fertility to many patients. However, the current promotion of the utilization of ART is still fraught with many obstacles. In this context, focusing on the realistic challenges of ART on its development in China, we will take a problem-oriented approach, utilize the relevant policies of ART in foreign countries as references, and put forward policy recommendations for the further implementation of ART, such as coordinating the balanced distribution of ART resources in the region, strengthening policy safeguards for ART, enhancing the institutional functioning of professional associations in medical ethics, and standardizing the application of ART treatments.

BACKGROUND:Previous studies found that the proliferative scar-specific long non-coding RNA lncRNA HSFAS is a novel biomarker that can be used in the diagnosis of hypertrophic scar,but how it functions in hypertrophic scar is not clear. OBJECTIVE:To investigate the role and mechanism of lncRNA HSFAS in hypertrophic scar.METHODS:Fresh scar tissue and surrounding normal skin tissue samples from three patients with hypertrophic scar were collected,and tissue immunofluorescence was used to detect the expression of lncRNA HSFAS in frozen sections of two skin tissues. Primary fibroblasts were isolated from proliferative scarred skin tissue and normal skin tissue and cultured by enzyme digestion method. Quantitative real-time PCR was used to detect the mRNA expression of lncRNA HSFAS in cells. The proteins bound to lncRNA HSFAS were detected by RNA pull-down combined mass spectrometry. GO and KEGG were used to analyze the main functions and pathways of lncRNA HSFAS involved in hypertrophic scar progression. The targeted binding of lncRNA HSFAS to proteins was determined by catRAPID and RPISeq website analysis. RESULTS AND CONCLUSION:Compared with normal skin tissue and fibroblasts from normal skin tissue,the expression of lncRNA HSFAS in human hypertrophic scar tissue and primary fibroblasts from hypertrophic scar tissue was significantly increased (P<0.05). There were 510 proteins clearly bound to lncRNA HSFAS by RNA pull-down combined mass spectrometry. The results of GO and KEGG analyses showed that these proteins were mainly involved in RNA splicing and processing,chromosome synthesis and separation,and cell cycle. Among them,the proteins involved in RNA splicing and processing included scaffold attachment factor B2 and DICER1,and the binding fraction with lncRNA HSFAS was higher. The results of bioinformatics analysis showed that lncRNA HSFAS was bound to scaffold attachment factor B2 and DICER1 proteins. To conclude,lncRNA HSFAS may affect gene expression by interacting with scaffold attachment factor B2 and DICER1 proteins to regulate RNA splicing and processing modification,thus promoting the occurrence and development of hypertrophic scar.

During the 14th Five-Year Plan period, the population of China has turned into a stage of negative growth, the fertility rate gradually declined, and the infertility rate gradually increased. The most effective treatment for infertility is assisted reproductive technology (ART), which has brought hope for fertility to many patients. However, the current promotion of the utilization of ART is still fraught with many obstacles. In this context, focusing on the realistic challenges of ART on its development in China, we will take a problem-oriented approach, utilize the relevant policies of ART in foreign countries as references, and put forward policy recommendations for the further implementation of ART, such as coordinating the balanced distribution of ART resources in the region, strengthening policy safeguards for ART, enhancing the institutional functioning of professional associations in medical ethics, and standardizing the application of ART treatments.

BACKGROUND:Previous studies found that the proliferative scar-specific long non-coding RNA lncRNA HSFAS is a novel biomarker that can be used in the diagnosis of hypertrophic scar,but how it functions in hypertrophic scar is not clear. OBJECTIVE:To investigate the role and mechanism of lncRNA HSFAS in hypertrophic scar.METHODS:Fresh scar tissue and surrounding normal skin tissue samples from three patients with hypertrophic scar were collected,and tissue immunofluorescence was used to detect the expression of lncRNA HSFAS in frozen sections of two skin tissues. Primary fibroblasts were isolated from proliferative scarred skin tissue and normal skin tissue and cultured by enzyme digestion method. Quantitative real-time PCR was used to detect the mRNA expression of lncRNA HSFAS in cells. The proteins bound to lncRNA HSFAS were detected by RNA pull-down combined mass spectrometry. GO and KEGG were used to analyze the main functions and pathways of lncRNA HSFAS involved in hypertrophic scar progression. The targeted binding of lncRNA HSFAS to proteins was determined by catRAPID and RPISeq website analysis. RESULTS AND CONCLUSION:Compared with normal skin tissue and fibroblasts from normal skin tissue,the expression of lncRNA HSFAS in human hypertrophic scar tissue and primary fibroblasts from hypertrophic scar tissue was significantly increased (P<0.05). There were 510 proteins clearly bound to lncRNA HSFAS by RNA pull-down combined mass spectrometry. The results of GO and KEGG analyses showed that these proteins were mainly involved in RNA splicing and processing,chromosome synthesis and separation,and cell cycle. Among them,the proteins involved in RNA splicing and processing included scaffold attachment factor B2 and DICER1,and the binding fraction with lncRNA HSFAS was higher. The results of bioinformatics analysis showed that lncRNA HSFAS was bound to scaffold attachment factor B2 and DICER1 proteins. To conclude,lncRNA HSFAS may affect gene expression by interacting with scaffold attachment factor B2 and DICER1 proteins to regulate RNA splicing and processing modification,thus promoting the occurrence and development of hypertrophic scar.

Objective:To analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Beijing in 2024, to investigate the infection status of reservoir hosts, vector organisms, and baseline human populations, and provide a scientific basis for formulating prevention and control strategies.Methods:Epidemiological surveys were conducted on all confirmed cases. Serum samples from healthy populations and reservoir hosts were collected for SFTSV antibody detection. Questing ticks were monitored using the flagging method. Real-time fluorescent quantitative PCR was employed to detect SFTSV in cases, reservoir hosts, and ticks. Positive samples underwent whole-genome sequencing and genetic evolution analysis.Results:In 2024, Beijing reported 15 locally infected cases with 4 deaths. The age of onset ranged from 50 to 80 years (median: 66 years). Cases showed a certain degree of geographical clustering, with June being the peak month of onset. The affected population was predominantly farmers, with a male-to-female ratio of 3∶2. Animal contact history emerged as a significant risk factor alongside tick bites. Parthenogenetic tick populations were identified in Pinggu district, while SFTSV-carrying ticks were detected in endemic areas (Mentougou, Shijingshan, and Fengtai Districts). Viral presence was also confirmed in ticks or dogs from non-endemic areas. Sequencing and phylogenetic analysis revealed stable clustering of strains into two distinct genotypes (A and B). Antibody-positive individuals were identified in healthy populations from non-endemic areas.Conclusions:The incidence of SFTS in Beijing is increasing, with natural viral circulation already established in non-endemic regions. Enhanced surveillance and adjusted prevention strategies are urgently needed.

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.