ObjectiveTo investigate the possible mechanism of action of Xibining Formula （膝痹宁） for cartilage damage in knee osteoarthritis （KOA） through the cyclic guanosine-adenosine monophosphate synthase （cGAS）- stimulator of interferon genes （STING） signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups （10 per group）， sham operation group， KOA model group， low-dose Xibining Formula group， high-dose Xibining Formula group， and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus （DMM） method in all groups but the sham surgery group. Two weeks after surgery， the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/（kg·d） and 14.32 g/（kg·d） respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/（kg·d） of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan （DMXAA） at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/（kg·d） via gavage， once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were measured by ELISA； pathological changes in cartilage tissue were observed using hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system； the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 （MMP3）， matrix metalloproteinase 13 （MMP13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS）， type-Ⅱ collagen （CⅡ） and aggregated proteoglycan （Aggrecan）， and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group， the KOA model group showed severe cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with the control group， serum level of IL-6， IL-1β， TNF-α in all the intervented groups decreased （P＜0.01）， while compared with high-dose Xibining Formula group， level of IL-6， IL-1β， and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased （P＜0.01）. Compared with the KOA model group， all the intervention groups exhibited alleviated cartilage pathological changes， signi-ficantly reduced Mankin scores， significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly decreased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with high-dose Xibining Formula group， high-dose Xibining Formula + agonist group showed cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway， decreasing matrix degradation-related proteins， and elevating matrix composition-related proteins.

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent environmental pollutants that are detected globally not only in the natural environment such as air, water, and soil, but also in animal and humans, posing a potential threat to human health. Epidemiological studies showed that PFAS exposure is closely associated with adverse pregnancy outcomes such as miscarriage, preterm birth, low birth weight and length. Studies showed that women of childbearing age have a higher risk of miscarriage and preterm birth after PFAS exposure before and during pregnancy, but the results of many studies at home and abroad are inconsistent, and it is certain that PFAS exposure is negatively correlated with birth weight and length. The mechanism of action of PFAS exposure inducing adverse pregnancy outcomes may include multiple pathways, involving oxidative stress, changes in endocrine hormone levels, abnormal glucose and lipid metabolism, and gene expression. However, the specific mechanism is still unclear. This article reviewed recent epidemiological studies on the relationships between PFAS exposure and adverse pregnancy outcomes, focusing on the effects of PFAS exposure on pregnancy outcomes, and summarized the potential mechanisms of action. This article aimed to clarify the reproductive toxicity of such chemicals, arouse the concern of women of childbearing age and pregnant women, and provide scientific basis for relevant prevention and intervention measures.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

Objective:To discuss and analyze the current situation of the application and approval of new Chinese medicine in China; To provide a reference for the research and development of new Chinese medicines in the future.Methods:The drug registration data were retrieved from Xanda database from January 1, 2016 to December 31, 2022, and the information of new approval and application of new Chinese medicines during this periods was systematically organized from the aspects of the number of registered varieties, registration categories, therapeutic areas, prescription sources, dosage form distribution, development cycle, clinical research and control drugs.Results:From 2016 to 2022, the total number of application for new Chinese medicines was 265. The number of registration classification 1.1 of new compound drugs was the largest. The dosage forms of new drugs were mainly granules, capsules, and tablets. Indications mainly focused on respiratory, neuropsychiatric, digestion and cardio-cerebrovascular diseases, etc. From 2016 to 2022, the total number of approval for new Chinese medicines was 29, of these, 19 from 2021 to 2022. The number of registration classification 1.1 of new Chinese medicines was the largest. The treatment fields are mainly respiratory system, gynecology and neuropsychiatric diseases, etc. The dosage forms of new drugs were mainly granules, capsules, and tablets. The number of drugs in prescriptions was 6-15. High-frequency drugs included Glycyrrhizae Radix et Rhizoma, Ephedrae Herba, Scutellariae Radix, Pinelliae Rhizoma, Poria and Gypsum Fibrosum. Phase Ⅱ and phase Ⅲ of the clinical trials had the largest number. The development period was approximately between 10-20 years. The most prescription source of new drugs was clinical experienced prescriptions and hospital pharmaceutics.Conclusion:The results show that China has been gradually building-up a relatively complete ecosystem for research and development of new Chinese medicines, helping to develop more high-quality Chinese medicines.

OBJECTIVE To explore the effect and mechanism of warming channels and activating blood circulation external treat-ment to alleviate peripheral hyperalgesia in knee osteoarthritis(KOA)based on NGF/TrKA signaling pathway.METHODS 30 SD rats were randomly divided into normal group,KOA group and Yiceng group.KOA model was established by anterior cruciate ligament transection(ACLT).14 days after model establishment,rats in Yiceng group were treated with Yiceng patch.The peripheral pain threshold of rats was measured at different time points.The cartilage sections were stained with HE,Aggrecan and type II collagen.The synovial sections were stained with HE,Sirius red,silver and performed with immunostaining.The protein expression of key molecules NGF and TrKA of NGF/TrKA signaling pathway,inflammatory index IL-1β,pain mediator TRPV1,pan-neural mark-ers PGP9.5 and S100 in synovium and complexes transported to dorsal root ganglia(DRG)tissues via nerve endings was determined by Western Blot.The corresponding gene expression was determined by qPCR.The levels of NGF and SP in peripheral blood of rats were determined by ELISA.RESULTS Compared with the KOA group,the cold allodynia and mechanical allodynia thresholds of the rats in the Yiceng group increased(P<0.05,P<0.01);the protein and gene expression of NGF,TrKA,TRPV1,IL-1β,PGP9.5 in the synovial tissue decreased(P<0.05,P<0.01);the protein and gene expression levels of TRPV1,PGP9.5,S100 in the DRG tissue were downregulated(P<0.05,P<0.01).CONCLUSION The warming channels and activating blood circulation external treatment can inhibit the NGF/TrKA signaling pathway,downregulate the gene and protein expressions of NGF,TrKA,TRPV1,IL-1β,PGP9.5,and may inhibit the sprouting of sensory nerve fibers and improve the peripheral hyperalgesia state of rats with KOA.

In 2024, the American College of Gastroenterology (ACG) and the American Society for Gastrointestinal Endoscopy (ASGE) comprehensively updated the quality indicators for colonoscopy. This update aims to enhance the quality of colonoscopy, thereby more effectively reducing the inci-dence of colorectal cancer. The update contents include optimization of traditional quality control indicators, as well as the introduction of new assessment standards, such as the detection rate of sessile serrated lesions. Key priority indicators, including adenoma detection rate and adequate bowel preparation rate, have been further refined and quantified to ensure their operability in clinical practice. The updated indicator system emphasizes a balanced focus on both outcome evaluation based on long-term clinical data and process quality assessments, further underscoring the scientific nature and standardization of these quality control measures. The authors review the quality control indicators of the updated version and provide a systematic analysis of the clinical significance and specific operational guidelines for priority indicators. Additionally, they explore the critical role of these quality control measures in improving colonoscopy quality and reducing the risk of missed diagnoses. The aim of this review is to promote the further refinement and implementation of quality control standards, thereby providing stronger support for early prevention and treatment of colorectal cancer.

In 2024, the American College of Gastroenterology (ACG) and the American Society for Gastrointestinal Endoscopy (ASGE) comprehensively updated the quality indicators for colonoscopy. This update aims to enhance the quality of colonoscopy, thereby more effectively reducing the inci-dence of colorectal cancer. The update contents include optimization of traditional quality control indicators, as well as the introduction of new assessment standards, such as the detection rate of sessile serrated lesions. Key priority indicators, including adenoma detection rate and adequate bowel preparation rate, have been further refined and quantified to ensure their operability in clinical practice. The updated indicator system emphasizes a balanced focus on both outcome evaluation based on long-term clinical data and process quality assessments, further underscoring the scientific nature and standardization of these quality control measures. The authors review the quality control indicators of the updated version and provide a systematic analysis of the clinical significance and specific operational guidelines for priority indicators. Additionally, they explore the critical role of these quality control measures in improving colonoscopy quality and reducing the risk of missed diagnoses. The aim of this review is to promote the further refinement and implementation of quality control standards, thereby providing stronger support for early prevention and treatment of colorectal cancer.

Objective:To investigate the molecular expression and pathological features of endothelial cell (EC) in a murine model of choroidal neovascularization (CNV) based on single-cell RNA sequencing (scRNA-seq).Methods:Six C57BL/6 mice aged 6-8 weeks were randomly divided into two groups, with 3 mice in each group.Bilateral eyeballs were enucleated.The choroidal tissues from the two groups were isolated by shearing the complex and scraping the choroid, respectively.Single-cell suspension was prepared by continuous digestion with trypsin/type Ⅰ collagenase at 37 ℃, and the cell viability and EC ratio were detected by flow cytometry to determine the preparation method of single-cell suspension.Another 6 mice were randomly assigned into the control group and the CNV group, with 3 mice in each group.The CNV model was induced by laser photocoagulation and single-cell suspensions were prepared 7 days after modeling.Gene expression library construction was performed using the Chromi-um (10x Genomics) instrument.High throughput sequencing was performed using the Illumina Novaseq6000 to obtain the expression matrix.The EC subpopulations were classified according to previous researches and the Cellmarker database.Pseudo-time analysis was performed in EC, revealing the gene expression matrix of different states.CNV-EC were further selected with preliminary analysis of the expression characteristics.Another 6 mice were selected to establish the CNV model and eyeball frozen sections were prepared 7 days after modeling.Expression and distribution as well as the area percentage of EC marker Pecam1, mitochondrial outer membrane proteins Tomm20 and mt-Co1, and capillary markers Kdr and Plvap were observed by immunofluorescence staining, and the vascular diameter was calculated.The use and care of animals followed the ARVO statement.This study protocol was approved by the Experimental Animal Welfare and Ethics Committee of Air Force Military Medical University (No.20200181).Results:The cell viability of the single-cell suspension prepared from choroidal-scleral fragments and choroidal scrapings was 99.4% and 99.1%, respectively, both of which met the sequencing requirements.The percentage of EC detected by flow cytometry was approximately 1.58%.The scRNA-seq result revealed that both the normal control and CNV groups contained 13 choroidal cell clusters.Compared with the normal control group, the proportions of rod/cone photoreceptor cells, EC and hematopoietic cells all increased, while the retinal pigment epithelium (RPE) and Schwan cells reduced in the CNV group.Among all clusters, EC constituted 18.4%.The pseudo-time analysis demonstrated that EC could be further divided into 4 states.The percentage of state 2 EC was 29.1% in the CNV group, which was significantly higher than 9.5% in the normal control group.Differentially expressed gene analysis showed that the expression of mitochondrion-related genes, including mt-Nd4 and mt-Atp6, were upregulated in state 2 EC, while capillary-related genes, including Kdr and Esm1, were downregulated.Immunofluorescent staining revealed that the area of Tomm20 and mt-Co1 in Pecam1-positive EC in the CNV area was (19.50±4.68)% and (4.64±2.82)%, respectively, which were both higher than (3.00±2.09)% and (0.18±0.34)% in normal area ( t=7.88, 3.84; both at P<0.01). The area of Kdr and Plvap in Pecam1-positive EC in the CNV area was (1.50±0.29)% and (0.79±0.97)%, respectively, which were both lower than (31.30±5.44)% and (10.43±2.28)% in the normal area ( t=13.40, 9.48; both at P<0.01). The vascular diameter in the CNV area was (5.52±1.85)μm, which was larger than (4.21±1.84)μm in the normal area ( t=9.57, P<0.001). Conclusions:When CNV occurs, the proportion of EC in choroid increases, and CNV-EC shows pathologic features of mitochondrial metabolic activation and loss of capillary properties, suggesting the mitochondrial activation of EC may play a role in the formation of CNV.

Porto-sinusoidal vascular disease (PSVD) is an entity characterized with portal hypertension (PH) in the absence of cirrhosis, the related risk factors, and imaging evidence of obstructed portal vein, hepatic vein and inferior vena cava. Its prevalence varies significantly between East and West countries. Until now, the etiologies have been classified as autoimmune, hematologic, and prethrombotic conditions, infections, toxins or drugs, and genetic or metabolic disorders. However, the definite cause remains unknown. Diagnosis is based on three histopathological features: obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. The clinical manifestations of early PSVD are nonspecific, whereas those at a late stage are similar to cirrhosis. The imaging detection mainly reveals the PH signs and complications, but the liver stiffness is normal or slightly increased, necessitating a liver biopsy for PVSD diagnosis. PSVD treatment is similar to liver cirrhosis; however, the prognosis is better. In order to gain a thorough understanding of PSVD, the epidemiology, pathogenesis, clinical diagnosis, and treatment are discussed in this article.