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 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.

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.

Objective: To explore the intra-host genetic evolution of HIV-1 pol gene via follow-up for treatment-naïve HIV infections, and estimate the infection time with Bayesian coalescent theory, so as to support the evaluation of HIV epidemic. Methods: Five cases were recruited and followed up. The pol gene fragments were amplified for the characteristics of transmitted drug resistance ( TDR ) by RT-PCR. Bayesian coalescent theory was utilized to construct maximum clade credibility ( MCC ) tree for genetic evolution and calculate the time to the most recent common ancestor ( tMRCA ). Results: The five cases were all male, and aged from 27 to 50 years old.Five to nine sampling times were obtained from each case, and the pol gene sequences from each case formed a unique subcluster (posterior probability: 100% ), with different evolution characteristics, in the MCC tree. The three cases in primary HIV-1 infection were estimated to be infected one to five months before the first positive reaction of HIV screening, whereas the two HIV-1 diagnosed cases at first screening were extrapolated to get infected fourteen months and seven months before diagnosis, respectively. One case with acute HIV-1 infection carried TDR mutation ( M46I ) , expressing fast disease progress and quasispecies variation. Conclusions The general infection time can be estimated by analyzing the characteristics of intra-host genetic evolution of HIV-1 pol gene with Bayesian coalescent theory, and this method can help to estimate the HIV epidemic.

A double burden of overweight/obesity and malnutrition during childhood is a major concern in China. Dietary intakes in this critical period affect children's physical and cognitive development, and also have health consequences in later life. Therefore, establishing healthy eating habits that will endure is crucial for children. Nutrition education is an effective way in improving nutrition knowledge and attitudes, and healthy eating behaviors. Diverse forms of nutrition improvement programs that targeting children, family, teachers, and school settings have been conducted in many developed countries. However, due to the differences of genetic background, household environment as well as dietary patterns between Chinese children and children from other countries, the existing nutrition education programs for children abroad might not be appropriate for children in China. Thus, nutrition education programs that consider Chinese nutrition-related policies and food supply as well as the local educational resources are required for Chinese children. This review summarized nutrition-related policies and legislations in China and developed countries. A series of evidence-based nutrition education programs that combined educational strategies and environmental supports conducted in the Southwest China Childhood Nutrition and Growth Study were presented. These programs can serve as example models for adopting nutrition interventions to improve nutrition and health status of children in different regions of China.

Objective To evaluate the clinical effect of dextromethorphan and its effect on daily living of patients with poststroke pseudobulbar affect. Methods Sixty patients with poststroke pseudobulbar affect admitted in our hospital from May 2013 to October 2016 were enrolled. Then they were randomly divided into the control group and the treatment group,with 30 patients in each group.Patients in the control group were treated with fluox-etine therapy and patients in the treatment group were treated with dextromethorphan therapy.The center for neuro-logic study lability scale(CNS-LS)and activity of daily living(Barthel index,BI)before and 30 days after the treat-ments in the two groups had been accessed. Results Thirty days after the treatment,CNS-LS of the treatment group had obvious improvement compared with that before treatment(P < 0.01),but CNS-LS of the control group had no obvious improvement compared with that before treatment(P > 0.05). And significant improvement has been found 30 days after the treatment between the two groups(P<0.01).Furthermore,significant difference was found on BI between these two groups(P<0.05).Conclusions Dextromethorphan is effective in treatment of pa-tients with poststroke pseudobulbar affect and it can improve the activity of daily living of these patients.

Objective To observe the clinical effects of breaking blood expelling stasis method of traditional Chinese medicine (TCM) combined with edaravone on patients with acute hypertensive intra-cerebral hemorrhage and preliminarily discuss its protection mechanism on this disease. Methods Ninety-two patients with hypertensive intra-cerebral hemorrhage within 72 hours after occurrence admitted to Zengcheng District People's Hosipital of Guangzhou from May 2013 to December 2017 were enrolled, they were divided into conventional therapy group and combined treatment of TCM and western medicine group by random numbers produced by a computer, 46 cases in each group. The conventional therapy group was treated with conventional therapy, and the combined treatment of TCM and western medicine group was treated with conventional therapy, additionally the treatment of Poxue Zhuyu decoction (the ingredients of the decoction: leech 10 g, gradfly 10 g, rhubarb 15 g, cattail pollen 5 g, trichosanthes fruit 10 g, radix notoginseng 5 g, colla plastri testudinis 10 g, grassleaf sweetflag rhizome 10 g, ground beetle 3 g, dried lacquer 3 g, peach seed 10 g) and edaravone for 10 days. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were tested by enzyme-linked immunosorbent assay (ELISA) before and 7 days after treatment in the two groups; and the differences in National Institutes of Health stroke scale score (NIHSS) before and 14 days, 90 days after treatment as well as the changes of brain edema around the hematoma 14 days after treatment were compared between the two groups, and the incidence of adverse reaction was observed. Results After treatment, the levels of TNF-α, IL-6 and intra-cerebral hemorrhage quantities in the two groups were all decreased compared with those before treatment, and the degrees of decrease of TNF-α and cerebral hemorrhage volume in combined treatment of TCM and western medicine group were more significant than those in the conventional treatment group [TNF-α (ng/L): 21.00±6.10 vs. 29.40±11.33, cerebral hemorrhage volume (mL): 5.23±0.60 vs. 8.50±0.64, both P <0.05]. The IL-6 in the two groups were recovered to approximately normal levels after the treatment (ng/L: 13.60±5.36 vs. 15.40±6.13, P > 0.05). With the prolongation of therapeutic time, the scores of NIHSS of the two groups were significantly lowered than those before treatment, and the degree of reduction in the combined TCM and western medicine group on 90 days after treatment was more obvious than that of the conventional treatment group (4.34±0.67 vs. 7.73±0.61, P < 0.05). The volumes of edema around hematomas were increased after treatment in the two groups, but the degree of increase in combined treatment of TCM and western medicine group was slower than that of the conventional group (cm3: 7.57±0.64 vs. 10.16±0.60, P < 0.05). There was no statistical significant difference in the incidence of adverse reactions in comparison between the combined treatment of TCM and western medicine group and conventional therapy group [18.2% (8/44) vs. 20.5% (9/44), P > 0.05]. Conclusions Using breaking blood expelling stasis and edaravone for treatment of acute hypertensive intra-cerebral hemorrhage can accelerate the absorption of brain hematoma and improve the neurological function, and its mechanism may be relevant to the inhibition of some inflammatory factors.