ObjectiveTo investigate the liver-protecting and anti-liver fibrosis effects of astragaloside Ⅳ （AS-Ⅳ） in vitro and in vivo， as well as its mechanism of action in intervention against liver fibrosis. MethodsIn the animal experiment， C57BL/6J mice were divided into control group， model group， low-dose AS-Ⅳ （20 mg/kg） group， and high-dose AS-Ⅳ （80 mg/kg） group. The mice were given intraperitoneal injection of carbon tetrachloride for 6 weeks to induce liver fibrosis， and since week 3 of injection， the mice in the low-dose AS-Ⅳ group and the high-dose AS-Ⅳ group were given AS-Ⅳ by gavage at a dose of 20 mg/kg and 80 mg/kg， respectively. The serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured after 4 weeks of administration， as well as the serum levels of hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ N-terminal peptide （PⅢNP）， and collagen type Ⅳ （Col-Ⅳ）. HE staining， picrosirius red staining， and Masson staining were used to observe liver histopathology and collagen deposition； RT-qPCR was used to measure the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue， and Western blot was used to measure the protein expression levels of α-smooth muscle actin （α-SMA）， collagen type Ⅲ （Col-Ⅲ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated PI3K （pPI3K）， protein kinase B （Akt）， and phosphorylated AKT （p-Akt） in liver tissue； transcriptome sequencing was performed for liver tissue to identify differentially expressed genes and perform a bioinformatics analysis. In the cell experiment， transforming growth factor-β （TGF-β） was used to induce the activation of LX-2 cells， and the PI3K inhibitor LY294002 and the PI3K activator 740 Y-P were used for intervention. The cells were divided into control group， model group， AS-Ⅳ group， LY294002 group， and AS-Ⅳ+740 Y-P group， and the cells were harvested after 36 hours of intervention. Changes in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K/PI3K， and pAkt/Akt in LX-2 cells were measured， as well as changes in the relative mRNA expression levels of Acta2， Col1a1， and Col3a1. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the animal experiment， compared with the model group， the AS-Ⅳ treatment group had significant reductions in the serum levels of ALT， AST， HA， LN， PⅢNP， and Col-Ⅳ （all P<0.01）， the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue （all P<0.05）， and the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） in liver tissue （all P<0.05）. In the cell experiment， compared with the control group， the model group had significant increases in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） after TGF-β induction （all P<0.05）； compared with the model group， the AS-Ⅳ group had significant reductions in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） （all P<0.05）， and both the AS-Ⅳ group and the LY294002 group had significant reductions in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， Col1a1， and Col3a1 （all P<0.05）. Compared with the AS-Ⅳ group， there were significant increases in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， col1a1， and Col3a1 after 740 Y-P intervention （all P<0.05）. ConclusionAS-Ⅳ can inhibit hepatic stellate cell activation and improve liver fibrosis， possibly by inhibiting the PI3K/Akt signaling pathway.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

In modern society， the comorbidity of insomnia with amnesia has shown a significantly increasing incidence and become increasingly severe， emerging as a public health issue that endangers people's physical and mental health and quality of life. Anmei Dan （AMD）， originally recorded in the Shishi Milu by CHEN Shiduo in the Qing Dynasty， possesses profound theoretical foundations and distinct clinical advantages in ameliorating insomnia with amnesia. Basic research has unequivocally confirmed its definite therapeutic effects on insomnia with amnesia and revealed partial mechanisms. AMD is therefore a veritable classic prescription embodying the principle of treating different diseases with the same method for insomnia and amnesia. However， few researchers have reviewed the related research progress. This article systematically summarized the theoretical connotations of traditional Chinese medicine in treating insomnia with amnesia， delineated the multi-component material basis of AMD in ameliorating insomnia with amnesia （including various chemical components such as ginsenosides， jujubosides， and salvianolic acids）， and evaluate its multi-dimensional clinical efficacy （e.g.， prolonging total sleep time， improving sleep efficiency， and enhancing memory）. Moreover， it systematically summarizes the multi-pathway mechanisms of action. The results indicate that AMD has a clear material basis， definite clinical efficacy， and a favorable safety profile in ameliorating insomnia and amnesia. AMD may exert the therapeutic effect by regulating sleep-wake rhythms， enhancing synaptic plasticity， inhibiting neuroimmune inflammation， and modulating autophagy， oxidative stress， and energy metabolism. In conclusion， AMD exerts synergistic effects through multi-component， multi-dimensional， and multi-pathway approaches， serving as an important prescription for enriching and developing the theory of treating different diseases with the same method for insomnia with amnesia.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

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.

Objective: To analyze the burden of bipolar disorder among adolescents aged 10-24 in China from 1990 to 2021 and its trend of change, so as to provide theoretical basis for the prevention and treatment of bipolar disorder. Methods: The latest data from the Global Burden of Disease (GBD) database in 2021 were selected. The Joinpoint regression model, age-period-cohort (APC) model, and bayesian age-period-cohort (BAPC) model were used to analyze and predict indicators such as the age standardized incidence rate and age standardized disability adjusted life year (DALY) rate of bipolar disorder among Chinese adolescents, and the average annual percent change (AAPC) was calculated. Results: From 1990 to 2021, the overall age standardized incidence rate (1990:22.92/100 000, 2021:23.17/100 000) showed an upward trend ( AAPC=0.03, t=8.20, P <0.01) and change trend of age standardized DALY rate (1990:33.61/100 000, 2021:33.76/100 000) was relatively flat ( AAPC=0.01, t= 0.99 , P =0.32). From 1990 to 2021, age standardized incidence rate and age standardized DALY rate of girls were higher than boys ( χ 2=16.38, P <0.01). The net drift values for the incidence rate and DALY rate of bipolar disorder among Chinese adolescents aged 10-24 years were -0.23% and -0.22%, respectively. The highest incidence rate of bipolar disorder among Chinese adolescents aged 10-24 years was observed in the 15-19 age group, with a rate of 33.14/100 000; the highest DALY risk was in the 20- 24 age group, with a rate of 57.26/100 000. The lowest incidence risk and DALY risk RR values for bipolar disorder among Chinese adolescents aged 10-24 years were observed in 2017-2021, with RR values of 0.99 (95% CI =0.97-1.00) and 0.98 (95% CI = 0.97- 0.99), respectively ( P <0.05). Similarly, the lowest incidence risk and DALY risk RR values for this age group were observed in the 2000-2004 birth cohort, both of which were 0.86 (95% CI =0.84-0.87) ( P <0.05). It was projected that the overall age standardized incidence rate and age standardized DALY rate of bipolar disorder among Chinese adolescents aged 10-24 years will continue to increase from 2022 to 2031, reaching 24.10/100 000 and 34.90/100 000, respectively, by 2031. Conclusions From 1990 to 2021, both the age standardized incidence rate and age standardized DALY rate of bipolar disorder among Chinese adolescents shows an upward trend. Special attention should be given to female adolescents, with a focus on controlling the age standardized incidence rate of bipolar disorder among 15-19 year-old adolescents and the age standardized DALY rate among 20-24 year-old ones. Efforts should be enhanced to increase awareness and screening for bipolar disorder among adolescents.

Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.