ObjectiveThis paper aims to explore the in vitro anti-psoriasis activity and potential mechanism of Kangfuxin liquid （KFX liquid）， providing experimental evidence for the anti-psoriasis effect of KFX liquid. MethodsFirstly， the uninduced human immortalized keratinocyte cells （HaCaT cells） were divided into seven groups， namely the control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. After being treated with different concentrations of KFX liquid， the effect of KFX liquid on the normal cell proliferation was detected by using the cell counting kit-8 （CCK-8） method. Secondly， the uninduced HaCaT cells were divided into six groups， namely the control group and recombinant human interleukin-7A （rh-IL-7A） groups with different doses （5， 10， 50， 100， 120 g·L^-1）. After being treated with different concentrations of recombinant human interleukin-17A （rh IL-17A） liquid， the effect of rh IL-17A on cell proliferation was detected. The optimal induction concentration was screened. Then， normal HaCaT cells were divided into a control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. Except for the control group， the other groups established psoriasis cell models with the optimal induction concentration of rh IL-17A. After being treated with different concentrations of KFX liquid， the effects of KFX liquid on the psoriasis-like HaCaT cell proliferation were investigated. Finally， the uninduced HaCaT cells were divided into six groups， namely the control group， rh IL-17A group， methotrexate （MTX） group， and KFX liquid groups with different doses （20， 40， 80 g·L^-1）. Except for the control group， the other groups used the optimal induction concentration of rh IL-17A to establish psoriasis cell models. After being treated with different drugs， the cell migration levels were detected through scratch assays， and real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the relative mRNA expression levels of Ki-67 antigen （Ki67）， S100 calcium-binding protein A7 （S100A7）， S100 calcium-binding protein A8 （S100A8）， and S100 calcium-binding protein A9 （S100A9）， thereby comprehensively evaluating the in vitro anti-psoriasis activity of KFX liquid. By detecting the relative mRNA expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and chemokine-20 （CXCL-20） inflammatory-related factors in psoriasis-like HaCaT cells and the protein expression levels of Janus kinase 3 （JAK3）， phosphorylated Janus kinase 3 （p-JAK3）， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）， the mechanism was explored. ResultsCompared with that of control group， when treated with 80 g·L^-1 KFX liquid for 72 h （P<0.05） and at different times with 160 g·L^-1 KFX liquid， the HaCaT cell proliferation activity was significantly affected （P<0.01）， while the other concentrations of KFX liquid had no significant differences in cell morphology and cell proliferation activity at different times， indicating that the KFX liquid is relatively safe for HaCaT cells and has no obvious toxic side effects. Compared with that of control group， when treated with different concentrations of rh IL-17A for 24 h， the HaCaT cell proliferation activity was significantly enhanced， and the cell activity was the strongest when the concentration was 100 μg·L^-1 （P<0.05）， with a density close to 100% and intact cell morphology， indicating that 100 μg·L^-1 is the optimal concentration for inducing HaCaT cell proliferation. The results of the KFX liquid treatment on rh IL-17A-induced psoriasis-like cells show that the KFX liquid not only effectively inhibits the rh IL-17A-induced psoriasis-like HaCaT cell proliferation activity （P<0.01）， but also significantly reduces the migration ability of rh IL-17A-induced psoriasis-like HaCaT cells （P<0.01）， and the relative mRNA expression levels of Ki67， S100A7， S100A8， and S100A9 （P<0.01）. Moreover， the KFX liquid can significantly reduce the relative mRNA expression levels of IL-1β， IL-6， and CXCL-20 in rh IL-17A-induced psoriasis-like cells （P<0.01）， and significantly inhibit the phosphorylation levels of JAK3 and STAT3 proteins （P<0.05， P<0.01）. ConclusionThe KFX liquid has no obvious toxicity to uninduced HaCaT cells. It can inhibit rh IL-17A-induced psoriasis-like HaCaT cell proliferation， reduce the cell migration ability， and has good in vitro anti-psoriasis activity. Its action mechanism may be related to downregulating the expression levels of inflammation-related cytokines in the JAK3/STAT3 signaling pathway and inhibiting the phosphorylation levels of JAK3 and STAT3 proteins.

ObjectiveThis paper aims to explore the in vitro anti-psoriasis activity and potential mechanism of Kangfuxin liquid （KFX liquid）， providing experimental evidence for the anti-psoriasis effect of KFX liquid. MethodsFirstly， the uninduced human immortalized keratinocyte cells （HaCaT cells） were divided into seven groups， namely the control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. After being treated with different concentrations of KFX liquid， the effect of KFX liquid on the normal cell proliferation was detected by using the cell counting kit-8 （CCK-8） method. Secondly， the uninduced HaCaT cells were divided into six groups， namely the control group and recombinant human interleukin-7A （rh-IL-7A） groups with different doses （5， 10， 50， 100， 120 g·L^-1）. After being treated with different concentrations of recombinant human interleukin-17A （rh IL-17A） liquid， the effect of rh IL-17A on cell proliferation was detected. The optimal induction concentration was screened. Then， normal HaCaT cells were divided into a control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. Except for the control group， the other groups established psoriasis cell models with the optimal induction concentration of rh IL-17A. After being treated with different concentrations of KFX liquid， the effects of KFX liquid on the psoriasis-like HaCaT cell proliferation were investigated. Finally， the uninduced HaCaT cells were divided into six groups， namely the control group， rh IL-17A group， methotrexate （MTX） group， and KFX liquid groups with different doses （20， 40， 80 g·L^-1）. Except for the control group， the other groups used the optimal induction concentration of rh IL-17A to establish psoriasis cell models. After being treated with different drugs， the cell migration levels were detected through scratch assays， and real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the relative mRNA expression levels of Ki-67 antigen （Ki67）， S100 calcium-binding protein A7 （S100A7）， S100 calcium-binding protein A8 （S100A8）， and S100 calcium-binding protein A9 （S100A9）， thereby comprehensively evaluating the in vitro anti-psoriasis activity of KFX liquid. By detecting the relative mRNA expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and chemokine-20 （CXCL-20） inflammatory-related factors in psoriasis-like HaCaT cells and the protein expression levels of Janus kinase 3 （JAK3）， phosphorylated Janus kinase 3 （p-JAK3）， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）， the mechanism was explored. ResultsCompared with that of control group， when treated with 80 g·L^-1 KFX liquid for 72 h （P<0.05） and at different times with 160 g·L^-1 KFX liquid， the HaCaT cell proliferation activity was significantly affected （P<0.01）， while the other concentrations of KFX liquid had no significant differences in cell morphology and cell proliferation activity at different times， indicating that the KFX liquid is relatively safe for HaCaT cells and has no obvious toxic side effects. Compared with that of control group， when treated with different concentrations of rh IL-17A for 24 h， the HaCaT cell proliferation activity was significantly enhanced， and the cell activity was the strongest when the concentration was 100 μg·L^-1 （P<0.05）， with a density close to 100% and intact cell morphology， indicating that 100 μg·L^-1 is the optimal concentration for inducing HaCaT cell proliferation. The results of the KFX liquid treatment on rh IL-17A-induced psoriasis-like cells show that the KFX liquid not only effectively inhibits the rh IL-17A-induced psoriasis-like HaCaT cell proliferation activity （P<0.01）， but also significantly reduces the migration ability of rh IL-17A-induced psoriasis-like HaCaT cells （P<0.01）， and the relative mRNA expression levels of Ki67， S100A7， S100A8， and S100A9 （P<0.01）. Moreover， the KFX liquid can significantly reduce the relative mRNA expression levels of IL-1β， IL-6， and CXCL-20 in rh IL-17A-induced psoriasis-like cells （P<0.01）， and significantly inhibit the phosphorylation levels of JAK3 and STAT3 proteins （P<0.05， P<0.01）. ConclusionThe KFX liquid has no obvious toxicity to uninduced HaCaT cells. It can inhibit rh IL-17A-induced psoriasis-like HaCaT cell proliferation， reduce the cell migration ability， and has good in vitro anti-psoriasis activity. Its action mechanism may be related to downregulating the expression levels of inflammation-related cytokines in the JAK3/STAT3 signaling pathway and inhibiting the phosphorylation levels of JAK3 and STAT3 proteins.

Objective Based on the secreted frizzled-related protein 2(SFRP2)-Wnt/β-catenin signaling pathway,this study explored the effect and mechanism of Cuiru Keli(CRKL)in the treatment of postpartum hypogalactia.Methods A rat model of postpartum hypogalactia was established by gavaging 2 mL of 1.6 mg/mL bromocriptine mesylate to female rats on the third day after delivery.Female rats with a delivery time difference of less than 48 hours were selected and randomly assigned to 7 groups,including a normal group(without any modeling or medication),a model group,a CRKL low-dose group of model group model rats receiving CRKL at the dose of 3 g/kg,a CRKL medium-dose group of model rats receiving CRKL at the dose of 6 g/kg,a CRKL high-dose group of model rats receiving CRKL at the dose of 9 g/kg,a positive drug group of model rats receiving domperidone at the dose of 3 mg/kg,and a negative control(NC)group of model rats receiving normal saline.Each group contained 6 rats.Except for the normal and model groups,the remaining 5 groups were continuously administered with the respective intervention drugs at the specified doses by gavage once a day for 10 days.Changes in the total litter mass of the offspring in the 7 groups within 10 days were measured,and HE staining was performed to identify pathological changes in the mammary tissue(MT).Six groups of rats(excluding the positive control group)were used to observe the pathological changes of eosinophils in pituitary tissue.ELISA was performed to determine the content of prolactin(PRL)in serum,immunohistochemical staining was used to determine the expression of prolactin receptor(PRLR)in MT,and RT-qPCR was used to determine the mRNA expression of genes related to lactation in MT.Network pharmacology and molecular docking were used to study the therapeutic effect and mechanism of CRKL on postpartum hypogalactia,particularly whether it acted through the SFRP2-Wnt/β-catenin signaling pathway.The mechanism of CRKL treatment was further validated by detecting mRNA(RT-qPCR)and protein expression(Western blot)of related pathway genes.Cell experiments were conducted using primary culture rat mammary epithelial cells(RMEC)from rat MT.RMEC were divided into four groups,including a normal group(primary culture RMEC,untreated),SFRP2 overexpression group(primary cultured RMEC treated with SFRP2 overexpression vector),SFRP2 overexpression+CRKL group(receiving treatment for SFRP2 overexpression group plus 10% drug-containing serum),and negative control group(primary culture RMEC treated with empty vector).The effect of CRKL on the expression of lactation-related genes FASN,CSN2,and GLUT1 mRNA after SFRP2 overexpression was detected by RT-qPCR.Results In this study,CRKL was administered at a dose of 3 g/kg in the CRKL low-dose group,6 g/kg in the medium-dose group,and 9 g/kg in the high-dose group(P<0.05 or P<0.01).Compared with the model group,CRKL at all doses significantly increased the total litter weight gain of the offsprings within 10 days(P<0.05 or P<0.01),and effectively increased lactation(P<0.01),the area of mammary lobules,and the size and filling of acinar cavities.CRKL at all doses also increased the number of eosinophils that secreted PRL in the pituitary gland of the postpartum hypogalactia rat model,and increased the content of PRL in the serum(P<0.05 or P<0.01).CRKL promoted the secretion and expression of PRL in postpartum hypogalactic model rats.In addition,it significantly promoted the expression of genes related to milk fat,milk protein,and lactose synthesis in MT(P<0.05 or P<0.01).Network pharmacology predicted that the Wnt signaling pathway might be a key pathway for CRKL in treating postpartum hypogalactia.The molecular docking results showed that related chemical components in CRKL had good binding ability with CCND1 and SFRP2.Compared with the model group,CRKL at all doses inhibited the expression of SFRP2 gene in vivo(P<0.01)and activated the mRNA and protein expression of CCND1 and c-Myc in the Wnt/β-catenin signaling pathway in MT(P<0.05 or P<0.01).Cell experiments showed that,compared to the normal group,SFRP2 overexpression reduced the mRNA expression of milk synthesis-related genes FASN,CSN2,and GLUT1 in RMEC(P<0.01).The CCK8 results indicated that 10% of the drug-containing serum was the effective concentration administered to cells(P<0.01).After administering drug-containing serum,the expression of the lactation-related genes FASN,CSN2,and GLUT1 were up-regulated(compared with the SFRP2 overexpression group,P<0.01).Conclusion CRKL alleviates postpartum hypogalactia through the SFRP2-Wnt/β-catenin signaling pathway.SFRP2 might be a potential new target for the diagnosis and treatment of postpartum hypogalactia.This reveals a new mechanism of CRKL in treating postpartum hypogalactia and promotes its clinical application.

Methods: This study enrolled 51 patients with LDK out of 382 patients with adult degenerative spinal deformity. Baseline information was reviewed including demographic data and complications. Sagittal spinopelvic alignments and global imbalance parameters were assessed on full-length X-ray images of the spine. Muscularity and the fatty infiltration area of the ES and multifidus (MF) were measured at the L4/5 level on preoperative magnetic resonance image to evaluate the lumbar erector muscle atrophy. Stratification by sagittal vertical axis (SVA) was performed: group 1 with SVA <100 mm and group 2 with SVA >100 mm, and these groups were compared. Spearman correlation and multivariable logistic regression analyses were performed to analyze and define risk factors of postoperative proximal junctional kyphosis (PJK). Results: Group 2 had lower ES and MF muscularity than group 1. ES muscularity correlated with SVA (r=−0.510, p<0.003), lumbar lordosis (r=−0.415, p<0.018), and postoperative PJK (r=−0.508, p<0.022). MF muscularity did not correlate with the above parameters. Multivariable logistic regression analysis verified ES muscularity (odds ratio [OR], 0.001; p<0.039) and SVA (OR, 1.034; p<0.048) as the risk factors for postoperative PJK. Conclusions ES atrophy, besides the MF, is an important predictor in distinguishing decompensated LDK from well-compensated ones. It plays an important role in compensatory mechanism, not only correlates with global sagittal imbalance but also ties to PJK after deformity corrective surgery.

Methods: A cohort of 54 consecutive patients with DLS and RO was included in the study. All the included patients underwent selective RO fusion and at least 2 years of follow-up. They were divided into two groups: group 1 with a curve <30° and group 2 with a curve ≥30°. The clinical outcomes were evaluated by the Oswestry Disability Index (ODI) and Numerical Rating Scale. The radiological assessment included RO location, offset and subluxated-disc orientation, Cobb angle, and coronal as well as sagittal alignments. Results: The offset value was greater in group 2 than in group 1 (13.4±4.7 mm vs. 9.3±3.5 mm, p<0.001). The subluxated disc was mainly oriented to the concave side in group 2 (15/21) but to the convex side in group 1 (20/33) (p =0.022). Group 2 had a higher rate of postoperative adjacent RO than group 1 (14/21 vs. 1/33, p<0.001). The ODI was comparable between both groups preoperatively but higher at the final follow-up in group 2 (34.9±9.5) than in group 1 (24.4±6.2). In the multiple logistic regression analysis, the thoracolumbar/lumbar curve was identified as the risk factor for postoperative adjacent RO (odds ratio, 1.400; p=0.007). The receiver operating characteristic analysis verified it with an area under the curve of 0.960 (p<0.001). Conclusions The clinical and radiological outcomes were maintained well in group 1 but not in group 2. Selective RO fusion in DLS with a lumbar curve <30° is a rational option. However, it should be avoided in those with a lumbar curve >30° because of a higher complication rate and a worse clinical outcome at the final follow-up.

Alzheimer's disease(AD)is a degenerative neurological disorder that can lead to cognitive decline,mental behavior abnormalities,and a reduced ability to undertake daily life activities.Tryptophan is an essential amino acid for the human body and is produced by three main metabolic pathways,namely kynurenine,5-hydroxytryptamine,and indole derivatives.Influencing the metabolites of tryptophan can ameliorate neuroinflammation in the brain and significantly improve cognitive ability,while the occurrence and development of AD are reduced.In this paper,we review the research literature on the use of tryptophan metabolism intervention in AD in the last 3 years from CNKI,PubMed,and other databases,and summarize its mechanism of action,with a view to providing a reference for further research on anti-AD drugs.

Alzheimer's disease(AD)is a degenerative neurological disorder that can lead to cognitive decline,mental behavior abnormalities,and a reduced ability to undertake daily life activities.Tryptophan is an essential amino acid for the human body and is produced by three main metabolic pathways,namely kynurenine,5-hydroxytryptamine,and indole derivatives.Influencing the metabolites of tryptophan can ameliorate neuroinflammation in the brain and significantly improve cognitive ability,while the occurrence and development of AD are reduced.In this paper,we review the research literature on the use of tryptophan metabolism intervention in AD in the last 3 years from CNKI,PubMed,and other databases,and summarize its mechanism of action,with a view to providing a reference for further research on anti-AD drugs.

Methods: This study included 60 patients with Lenke 1 AIS who underwent selective thoracic fusion surgery. Coronal spinal alignment parameters were analyzed preoperatively, postoperatively, and at the final follow-up. The postoperative FMS was divided into two groups: the balanced group (FMS ≤20 mm) and the unbalanced group (FMS >20 mm). An independent t-test was used to compare quantitative data between groups, and a chi-square test was used for qualitative data. Furthermore, binary logistic regression and receiver operating characteristics curve analyses were used to identify the risk factors for postoperative distal adding-on in AIS. Results: At 2-year follow-up, the unbalanced group was more likely to have adding-on (17 of 24 patients) than the balanced group (six of 36 patients; p<0.001). Twenty-three patients with distal adding-on had significantly greater preoperative and postoperative lower instrumented vertebrae (LIV) rotation, FMS, and FMS angle (FMSA) than those without postoperative distal adding-on. Binary logistic regression analysis selected three independent risk factors for adding-on incidence after surgery: FMS (odds ratio [OR], 1.115; 95% confidence interval [CI], 1.049–1.185; p<0.001), FMSA (OR, 1.590; 95% CI, 1.225–2.064; p<0.001), and postoperative LIV rotation (OR, 6.581; 95% CI, 2.280–19.000; p<0.001). Conclusions Achieving a balanced fusion mass intraoperatively is important to avoid postoperative distal adding-on, with FMS of <20 mm and FMS angle of <4.5°. Furthermore, correcting LIV rotation helps to decrease the incidence of postoperative distal addingon.

Objective:To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection.Methods:This multicenter cross-sectional parallel control study was conducted in 11 children′s hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman′s rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection.Results:A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum ( r=0.97 , P<0.01). The linear regression equation was PCT?venous serum=0.135+0.929×PCT peripheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods ( r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. Conclusions:There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

OBJECTIVE： To investigate the acute toxicity， long-term toxicity， skin irritation and anaphylaxis of Bee venom （BV） plastics， and to evaluate its preclinical safety. METHODS： The acute toxicity of BV plastics to rats was investigated after administration of high-dose， medium-dose and low-dose （144， 96， 48 mg/kg） of BV plastics. The long-term toxicity of BV plastics was investigated by continuous administration of high-dose， medium-dose and low-dose （72， 48， 24 mg/kg） of BV plastics for 28 days. The irritation of intact and damaged skin in rabbits with 8 mg/kg BV plastics was investigated by using the self-control method of left and right homologous body. The skin anaphylaxis of guinea pig were investigated after sensitized with 15 mg/kg BV plastics on the left back （on 0， 7th， 14th day） and stimulated with 15 mg/kg BV plastics on the right back. RESULTS： During the acute toxicity experiment with BV plastic，the weight of rats and the changes of viscera were normal，and there was no relevant toxic reaction. Long-term toxicity test results showed that no significant pathological changes were observed at 24 h after the last administration； the spleen index  of rats in BV low-dose group， testicular index in middle-dose group and epididymis index in high-dose and middle-dose groups were significantly increased， while PT in plasma of rats in BV medium-dose and low-dose groups was significantly prolonged （P＜0.05）. There were no abnormal changes in organ appearance， other organ index， coagulation index and blood biochemical index. All above indexes became normal at the end of 2-week recovery period. Skin irritation test showed that BV plastics could cause slight erythema and obvious scab on the skin of rabbits which along with little irritation on intact or damaged skin. Skin anaphylaxis test showed that BV plastics produced mild erythema in the skin of guinea pigs， belonging to light allergy. CONCLUSIONS： No acute or long-term toxicity is observed after transdermal administration of BV plastics， which is safe and only causes mild irritation and irritability to skin， indicating there is good safety of the plastic under experiment doses.