Application of different prognostic scores in liver transplantation decision-making for acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.

Effect of Circulating Plasma Cells on the Prognosis of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#to analyze the effect of circulating plasma cells(CPC) on the prognosis of patients with multiple myeloma(MM) in the era of new drugs, and to explore the new definition standard of primary plasma cell leukemia(pPCL).@*METHODS@#The clinical data of 321 patients with newly diagnosed MM and 21 patients with pPCL admitted to our hospital from January 2014 to May 2022 were retrospectively analyzed. According to the proportion of CPC in peripheral blood smears, all patients were divided into 4 groups: CPC 0% group(211 cases), CPC 1%-4% group(69 cases), CPC 5%-19% group(41 cases) and CPC≥20% group(21 cases). The clinical features of patients in each group were compared and the prognosis fators was analyzed.@*RESULTS@#The median OS of the four groups were 44.5,21.3,24.6 and 12.8 months, respectively. Among them, 295 patients(86.3%) were treated with new drugs, and the median OS of the four groups were not reached, 26.7, 24.6 and 14.9 months, respectively. As the survival curves of CPC 5%-19% group and CPC≥20% group were similar, the patients were divided into CPC<5% group and CPC≥5% group, the median OS of CPC<5% group was better than that in CPC≥5% (43.5 vs 22.3 months, P<0.001). In addition, the median OS of patients in the CPC 1%-4% group was also significantly lower than that in the CPC 0% group and similar to that in the CPC≥5% group. Multivariate analysis showed that 1%-4% CPC was an independent risk factor for the OS of patients with CPC<5%. The patients with CPC<5% were stratified by R-ISS staging, and the OS of R-ISS stage Ⅰ or stage Ⅱ with 1%-4% CPC was similar to that of R-ISS stage Ⅲ. The newly defined pPCL patients showed increased tumor load and obvious invasive characteristics. Multivariate analysis showed no independent prognostic factors for pPCL, and high-risk cytogenetic abnormalities(HRCA) had no significant effect on the prognosis.@*CONCLUSION@#The validity of IMWG's new pPCL definition standard was verified, and it was found that the survival of MM with 1%-4% CPC also is poor and the prognosis is very close to pPCL. In addition, the newly defined pPCL has unique clinical and biological characteristics.

Correlation between D-Dimer/Fibrinogen Ratio and Bleeding in Patients with Newly Diagnosed Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To further explore the better indicators for predicting the degree of bleeding associated with newly diagnosed acute promyelocytic leukemia (APL).@*METHODS@#A total of 131 patients with newly diagnosed APL were classified according to WHO bleeding scales before treatment and divided into two groups: scales 0, 1 and 2 were included in no severe bleeding group, scales 3 and 4 were included in severe bleeding group. The information of the patients were collected, including sex, age, hemoglobin (Hb), white blood cell (WBC) count and platelet (PLT) count, peripheral blood lymphocyte percentage (LYMPH%), peripheral blood monocyte percentage (MONO%), percentage of leukemic cells in pripheral blood and bone marrow, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, D-dimer (D-D), D-dimer/fibrinogen ratio (DFR).@*RESULTS@#Among 131 patients, 110 were classified as no severe bleeding, and 21 were severe bleeding. The results of univariate analysis showed that patients with severe bleeding had significantly higher percentage of leukemic cells in pripheral blood, WBC, D-D, and DFR, as well as longer PT and lower LYMPH%, compared to those with no severe bleeding. Multivariate analysis revealed that DFR (OR =1.054, 95%CI : 1.024-1.084, P < 0.001) and percentage of peripheral blood leukemic cells (OR=1.026, 95%CI: 1.002-1.051, P =0.033) were independent risk factors for severe bleeding. The area under ROC curve (AUC) of peripheral blood leukemic cells, D-D and DFR were 0.748, 0.736 and 0.809, respectively. There was no statistical difference between the peripheral blood leukemic cells and D-D in diagnostic efficacy (P =0.8708). Compared with D-D, DFR had a higher predictive value (P =0.0302). The optimal cut-off value of DFR was 16.50, with a sensitivity of 90.5% and a specificity of 70.0%.@*CONCLUSION@#DFR has a significant advantage in predicting the degree of bleeding associated with newly diagnosed APL. The greater the DFR value, the heavier the degree of bleeding. The risk of severe or fatal bleeding increases when DFR is greater than 16.50.

Effect of acupuncture at Weizhong (BL 40) on bladder urination function based on ultrasound / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture at Weizhong (BL 40) with deqi on bladder urination function.@*METHODS@#A total of 60 healthy subjects were randomized into an observation group and a control group, 30 subjects in each group. Under the guidance of ultrasound, acupuncture was applied Weizhong (BL 40) on both sides. In the observation group, the needling depth was reached to the tibial nerve, and lifting-thrusting twirling method was used to induce deqi. In the control group, the needling depth was reached to the superficial fascia, and no manipulation was operated to induce deqi. The needles were retained for 10 min and acupuncture was given once in both groups. The bilateral ureteral ejection frequency and volume of the bladder were observed by ultrasound before and after acupuncture, and the score of clinical evaluation scale of deqi sensation was observed in both groups.@*RESULTS@#After acupuncture, the frequency of bilateral ureteral ejection in the observation group and the bladder volume in the two groups were increased compared before acupuncture (P<0.05), and the frequency of bilateral ureteral ejection, bladder volume and score of clinical evaluation scale of deqi sensation in the observation group were higher than those in the control group (P<0.05, P<0.01).@*CONCLUSION@#Acupuncture at Weizhong (BL 40) with deqi improves the bladder urination function. Ultrasound visualization improves the standardization and safety of acupuncture, intuitively evaluates the acupuncture effect, and provides an objective basis for the correlation between meridian points specificity and zang-fu organs.

Jianpi Peiyuan acupoint thread embedding therapy for perimenopausal obesity: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy and safety of Jianpi Peiyuan acupoint thread embedding therapy on perimenopausal obesity (PMO).@*METHODS@#Ninety-six patients of PMO were randomly divided into an observation group (48 cases) and a control group (48 cases). The control group received health education and lifestyle intervention. On the basis of the treatment in the control group, the observation group was treated with acupoint thread embedding at the main acupoints of Shangwan (CV 13), Zhongwan (CV 12), Xiawan (CV 10), Yinlingquan (SP 9) and Fenglong (ST 40), etc. as well as the supplementary acupoints in accordance with the syndrome differentiation, once every 2 weeks for 8 weeks (4 times in total). The indexes of obesity (body mass index [BMI], waist circumference, hip circumference and body mass), modified Kupperman score, insomnia severity index (ISI) score, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score of the two groups were observed before and after treatment, and the safety was evaluated.@*RESULTS@#After treatment, BMI, waist circumference, hip circumference and body mass in the two groups were lower than before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, Kupperman, ISI and SAS scores in the observation group were lower than before treatment (P<0.05), and ISI score in the control group was lower than before treatment (P<0.05). Kupperman, ISI and SAS scores in the observation group were lower than those in the control group (P<0.05). There was no significant difference in SDS between the two groups or within groups (P>0.05). No serious adverse reactions occurred during the experiment.@*CONCLUSION@#Jianpi Peiyuan acupoint thread embedding therapy can reduce the degree of obesity in PMO patients, and improve patients' the perimenopausal symptoms, insomnia and anxiety, with good safety.

Application and research progress of ultrasound in acupuncture treatment / 中国针灸

The operation standardization, quantitative standard and safety of acupuncture treatment are important links in the development of acupuncture modernization. In recent years, with the continuous development of ultrasonic imaging technology, ultrasonic medicine has the characteristics of visualization, quantitative analysis and real-time dynamics, which could play a unique role in acupuncture treatment. In this paper, the research progress of the combined application of ultrasonic medicine and acupuncture treatment is described from three aspects: ultrasound guidance helping to standardize acupuncture operation, ultrasound guidance helping to improve and evaluate the clinical efficacy of acupuncture, and ultrasound guidance helping to improve the safety of acupuncture, aiming to providing new ideas for the application of modern medicine in traditional medicine.

Design, synthesis and antiplatelet activity evaluation of novel quinoxaline antagonists of protease activated receptor 4 (PAR4) / 药学学报

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by 1H NMR, 13C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC50 = 0.26 μmol·L-1) was 6.7 times than the lead compound A (IC50 = 1.73 μmol·L-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

Current situation and the latest progress in the treatment of pyoderma gangrenosum / 中华烧伤杂志

Pyoderma gangrenosum (PG) is a rare chronic inflammatory non-infectious skin dermatosis, and there is no clear treatment guideline for this disease at home and abroad. There are a variety of clinical treatment methods for PG, including local therapy and systemic application of glucocorticoids, immunosuppressants, intravenous immuno- globulin, and biologics. Glucocorticoids are the first-line drugs commonly used in clinical practice, and immunosuppressants can be used alone or in combination with glucocorticoids. In recent years, more and more evidence has shown that biologics are a new trend in the treatment of PG, mainly including tumor necrosis factor α inhibitors, interleukin-1 (IL-1) inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, rituximab, and small molecular inhibitors. This article summarizes the current status and latest progress in the treatment of PG, hoping to provide clinicians with ideas for the treatment of PG.

Regulation of Wnt/β-catenin Signaling Pathway in Renal Interstitial Fibrosis by Traditional Chinese Medicine：A Review / 中国实验方剂学杂志

Chronic kidney disease （CKD） has become a public health problem worldwide with renal interstitial fibrosis （RIF） serving as the important pathological feature and pathological outcome of various CKD. Therefore， anti-fibrosis therapy has important practical significance for delaying the progression of CKD and improving the prognosis of CKD patients. The Wnt/β-catenin signaling pathway is a conserved signaling pathway through evolution， which plays a vital role in organ formation， tissue homeostasis， and disease progression during embryonic development. A growing body of research has confirmed that the Wnt/β-catenin signaling pathway is one of the key signaling pathways in a variety of kidney diseases and its activation is closely related to RIF. RIF is aggravated by the specific regulation of the expression of downstream target genes， such as fibroblasts， zinc finger transcription factor 1 （Snail1）， M2 macrophages， matrix metalloproteinase-7 （MMP-7）， plasminogen activator inhibitor-1 （PAI-1）， and renin-angiotensin system（RAS）， and relieved by targeting the signaling pathways， such as Klotho， Dickkopf-related protein 1 （DKK1）， secreted frizzled-related protein 1 （Sfrp1）， and indocyanine green-001. In addition，the pathological view of RIF in traditional Chinese medicine （TCM） coincides with that in western medicine. Based on the etiology and pathogenesis of TCM in the combination of deficiency and excess， TCM regulates fibrosis-promoting mediators by tonifying deficiency， eliminating turbidity， removing the toxin， resolving stasis， and treating both symptoms and root causes in a multi-target， multi-layer， and multi-pathway manner to inhibit the Wnt/β-catenin signaling pathway and play an important role in renal protection. Therefore， this study reviewed the regulatory mechanism of the Wnt/β-catenin signaling pathway in RIF and the protective effect of targeting this signaling pathway on renal function and discussed the potential role of TCM in delaying the progression of RIF， which is expected to provide new targets and strategies for the prevention and treatment of RIF.

Systematic Effect of Modified Renshen Wumeitang in Regulation of GABA Signaling Pathway in Rats with Diarrhea / 中国实验方剂学杂志

ObjectiveTo investigate the effect of modified Renshen Wumeitang（MRWT） on the related regulatory factors of the γ-aminobutyric acid （GABA） signaling pathway in colon tissues of rats with diarrhea， and reveal the mechanism of MRWT in invigorating Qi， generating fluid， and checking diarrhea. MethodForty-eight SD immature rats were randomly divided into a blank group （n=12） and an experimental group （n=36）. The diarrhea model was induced in the experimental group by Sennae Folium combined with overstrain and improper diet for 14 days. Subsequently， the model rats were randomly divided into a model group （normal saline， 20 mL·kg-1）， a western medicine group （Medilac-Vita， 0.7 g·kg-1）， and a Chinese medicine group （MRWT， 35 g·kg-1）， with 12 rats in each group. The rats in the blank group received normal saline at 20 mL·kg-1， and those in the other groups were treated correspondingly， once a day for 7 days. The general condition， loose stool rate， and diarrhea index of the rats were observed daily. Immunohistochemistry was used to detect the optical density expression of GABA protein in the colon of rats. The content of phosphatidylinositol-3 kinase （PI3K）， protein kinase B2 （Akt2）， phosphorylated Akt （p-Akt）， and interleukin-1β （IL-1β） was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PI3K， Akt2， and GABA type A receptor subunit β2 （GABRB2） in the colon of rats were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the blank group， the model group showed worsened general condition， The difference was not statistically significant of loose stool rate and diarrhea index， increased expression of GABA protein （P<0.05）， elevated expression of PI3K， Akt2， p-Akt， and IL-1β （P<0.05， P<0.01）， and up-regulated PI3K， Akt2， and GABRB2 mRNA and protein expression （P<0.01）. Compared with the model group， the western medicine group and the Chinese medicine group showed the improved general condition， decreased loose stool rate and diarrhea index （P<0.01）， and decreased content of PI3K， Akt2， p-Akt， and IL-1β （P<0.05）. The Chinese medicine group displayed decreased mRNA expression of PI3K， Akt2， and GABRB2 （P<0.05， P<0.01） and down-regulated protein expression of GABA， PI3K， and GABRB2 （P<0.05， P<0.01）. The western medicine group exhibited down-regulated mRNA expression of PI3K，Akt2，and protein of PI3K （P<0.05）. ConclusionMRWT can regulate the GABA signaling pathway， reduce Cl- flow in intestinal epithelial cells to the intestinal lumen， and improve the imbalance of colonic fluid metabolism in the colon of diarrhea rats， thereby exerting its effects of invigorating qi， generating fluid， and checking diarrhea.

Simultaneous determination of 13 hormones in Testis et Penis Cervi using QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry / 中国中药杂志

A reliable QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) analysis method was developed for the simultaneous determination of 13 steroid hormones(nrolone, androstenedione, methyltestosterone, testosterone, norethindrone, medroxyprogesterone, progesterone, diethylstilbestrol, hexan-stilbestrol, estradiol, estrotriol, cortisone, hydrocortisone) in Testis et Penis Cervi. The samples were extracted with methanol and purified by QuEChERS. Subsequently, the samples were separated by ACQUITY BEH C_(18) column and detected in the multiple reaction monitoring(MRM) mode under electrospray ionization in the positive and negative ion modes, respectively. Significant differences in the content of thirteen steroid hormones in Testis et Penis Cervi between the sika deer at different periods and the red deer were observed. The content of testosterone(10.88 μg·kg~(-1)) and hydrocortisone(12.82 μg·kg~(-1)) in Testis et Penis Cervi derived from rutting sika deer was significantly higher than the content of testosterone(1.05 μg·kg~(-1)) and hydrocortisone(0.73 μg·kg~(-1)) from antler growth stage. The content of progesterone in Testis et Penis Cervi derived from red deer was 6.07 μg·kg~(-1), significantly higher than that from sika deer. The content of progesterone in the testicle of red deer reached 27.46 μg·kg~(-1), 4.5 times greater than that in the penis of red deer. The sensitivity, accuracy, and precision of the method can meet the detection requirements, and the developed method is suitable for the measurement of hormones in animal-derived food.

Effects of vestibular spontaneous nystagmus on visual smooth pursuit function / 中华耳鼻咽喉头颈外科杂志

Objective: The aim of the study is to analyze the effects of vestibular spontaneous nystagmus(SN) on the smooth pursuit function of visual ocularmotor system. Methods: A total of 46 patients with acute unilateral peripheral vestibular syndrome with SN (26 cases of vestibular neuritis, 6 cases of Ramsay Hunt Syndrome (RHS) with vertigo, 14 cases of sudden deafness with vertigo) were included in this work. In the study group, the results of SPT and SN test with videonystagmography(VNG) were also reviewed. Taking SPT parameters, the influence of SN intensity on SPT gain, asymmetry and waveform and their correlation were analyzed.SPSS19.0 software was used for statistical analysis. Results: Among the 46 patients, there were 36 cases of SN pointing to the healthy side(SN intensity range of 2.68°/s-32.53°/s), and 10 cases of SN pointing to the affected side (SN intensity range of 2.66°/s-16.54°/s). SN intensity was divided into 3 groups, including light(0.50°/s-5.00°/s), medium(5.01°/s-10.00°/s) and strong(>10.01°/s), accounting for 14 cases(30.4%), 18 cases(39.1%) and 14 cases(30.4%), respectively. The differences of the gain of SPT to the fast phase and slow phase direction in the overall groups and light, medium and strong groups of SN intensity respectively were statistically significant(ttotal=13.338, tlight=6.184, tmedium=8.436, tstrong=8.477, all of P<0.001). The difference of SPT gain in SN fast phase direction between groups with different SN intensity was statistically significant(F=9.639, P<0.001),there was no statistically significant difference in SPT gain between the groups on the SN slow phase direction(F=1.137, P=0.330).The SN intensity significantly negatively correlated with the SPT gain of the fast phase direction of SN (r=-0.433, P=0.003), that was, the SPT gain on the fast phase direction of SN decreased with the increase of SN intensity. There was no significant correlation between SN intensity and the gain of SPT on the slow phase direction of SN (r=-0.061, P=0.687). SPT waveform analysis showed that type I, type II and type III accounted for 8 cases(17.4%), 21 cases(45.6%) and 17 cases(37.0%), respectively. The corresponding mean values of SN intensity were (3.71±0.69)°/s, (7.44±1.88)°/s, (20.04±5.53)°/s, respectively, without type IV wave. The intensity of SN was positively correlated with the asymmetric value of the gain of SPT left and right(r=0.450,P=0.002). That was, with the increase of SN strength, the asymmetric value also increased, and the worse the asymmetry of the gain of SPT left and right pursuit was, the worse the SPT waveform was. Conclusion: SPT gain, asymmetry and SPT waveforms are all affected by SN, and the greater the intensity of SN, the greater the influence on the three. When SN is strong, type III waves may occur, suggesting that acute peripheral vestibular syndrome can also affect the visual ocularmotor systems.

Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β1/Smad Signal Pathway / 中国实验方剂学杂志

Objective:To study the protective effect of Xiayuxue Tang on adenine-induced renal fibrosis model in rats and its impact on Wnt/<italic>β</italic>-catenin and transforming growth factor <italic>β</italic>₁（TGF-<italic>β</italic>₁）/Smad signal pathway. Method:A total of 50 SPF-grade male SD rats were randomly divided into 5 groups： the normal group， the model group， the losartan group （9 mg·kg^-1） and low and high dose （2.43，4.86 g·kg^-1） of Xiayuxue Tang groups. The rat model of renal fibrosis was established by ig administration adenine （250 mg·kg^-1） for 24 consecutive days. The rats were then given the corresponding drugs for 30 consecutive days. The levels of serum creatinine（SCr） and blood urea nitrogen （BUN） were measured by enzyme-linked immunosorbent assay（ELISA）. The histopathological changes of renal tissues in rats were observed by hematoxylin and eosin （HE） staining. The collagen deposition in rat renal tissue was observed by Masson staining； the protein expression levels of Wnt5a， Wnt5b， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁， Smad4， Smad7 in renal tissue were detected respectively by immunohistochemistry（IHC） and Western blot. Result:Compared with the normal group， the results of each experimental group showed that SCr and BUN levels significantly increased in the model group （<italic>P</italic><0.01）. SCr and BUN levels decreased significantly after the intervention with the Xiayuxue Tang （<italic>P</italic><0.01）. Compared with the normal group， HE and Masson staining results showed that rats in the model group had severe renal interstitial damage and massive deposition of renal interstitial collagen. The renal interstitial tubule injury was relieved after the intervention with the Xiayuxue Tang， and the renal interstitial collagen deposition decreased. The results of IHC and Western blot showed that compared with the normal group， the expressions of Wnt5a， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁ protein in the kidney of rats up-regulated （<italic>P</italic><0.01）， while the expressions of Wnt5b and Smad7 protein down-regulated （<italic>P</italic><0.01）. After the intervention with Xiayuxue Tang， the expressions of Wnt5a， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁ protein down-regulated （<italic>P</italic><0.01）， while the expressions of Wnt5b and Smad7 protein up-regulated（<italic>P</italic><0.01）. There was no significant difference between the low-dose and high-dose groups with Xiayuxue Tang. Conclusion:Xiayuxue Tang has the protective effect on RIF rats induced by adenine， and its mechanism is related to the inhibition of Wnt/<italic>β</italic>-catenin and TGF-<italic>β</italic>₁/Smad signal pathway.

Toxicity of Chemotherapeutics Based on Viscera-state doctrine / 中国实验方剂学杂志

Malignant tumors are important diseases that threaten human health. Although targeting and immunotherapy have been gradually applied in the treatment of malignant tumors in recent years， which can alleviate the suffering of patients to a certain extent， there are still problems of large adverse reactions and easy drug resistance. At present， chemotherapy is still the main method for the treatment of malignant tumors. While killing tumor cells， chemotherapy also damages normal cells， which often leads to drug toxicity， such as bone marrow suppression， gastrointestinal adverse reactions， liver and kidney function damage， and oral mucosal reactions. Although modern medicines have a certain effect on the toxicity of chemotherapy drugs， there are still limitations. Traditional Chinese medicine（TCM） has a long history of treating malignant tumors， and considers that chemotherapy is a drug with toxin invading the body， exacerbating the "deficiency"， "toxin" and "stasis" of the body， causing damage to Qi， blood and organs， especially in spleen， stomach， liver and kidney， and leading to bone marrow suppression， liver and kidney function injury and other adverse reactions. Studies have confirmed that the use of TCM treatment has a better clinical efficacy. Therefore， new therapies shall be explored based on the basic theory of traditional Chinese medicine. As the core part of the theoretical system of TCM， Viscera-state doctrine is closely related to looking， listening， questioning and feeling the pulse of TCM， and has constantly developed and improved. It has important significance in guiding diagnosis and treatment of diseases. This study is guided by viscera-state doctrine of TCM and based on the etiology and pathogenesis of TCM. It starts with the clinical manifestations of common drug toxicity of chemotherapy drugs， such as bone marrow suppression， gastrointestinal adverse reactions， liver and kidney function damage， oral mucosal reactions， which are external signs of the toxicity of chemotherapeutic drugs， and associates pathological manifestations of viscera to physiological functions. From elephants and Tibetans， it systematically summarizes the viscera characteristics of various common chemotherapeutic drugs and provides new ideas and methods for clinical use of TCM in treating the toxicity of chemotherapeutic drugs， so as to promote the application of viscera-state doctrine in diagnosis and treatment of diseases.

Shengyutang Improves Learning and Memory Ability of Sleep Deprived Mice by Regulating Levels of Monoamine Neurotransmitters in Hippocampus / 中国实验方剂学杂志

Objective:To observe the effect of Shengyutang on the levels of monoamine neurotransmitters in the hippocampus， and explore its possible mechanism on improving the learning and memory abilities of sleep deprivation （SD） mice. Method:The 50 mice were divided into normal group， model group， estazolam group， Shengyutang low and high dose groups， with 10 mice in each group. A multi-platform water environment was used to prepare SD mouse models. The low and high-dose Shengyutang groups received intragastric administration of 12.5， 25 g·kg^-1， respectively. The mice in the model group were intragastrically administered with the same dose of normal saline daily for 8 weeks. Morris water maze experiment was used to observe the behavioral changes of SD mice in the evasion latency period， the number of crossing platforms， and the stay time in the target quadrant of each group. HE staining was used to observe the pathomorphological changes of the hippocampal tissue of each group. The expression levels of eight monoamine neurotransmitters including serotonin （5-HT），dopandne （DA），epinephrine （EP），norepinephrine （NE），5-hydroxyindole acetic acid（5-HIAA）， high vanillic acid （HVA）， levodopa（<italic>L</italic>-DOPA），and 3，4-dihydroxyphenylacetic acid（DOPAC）were detected by high performance liquid chromatography， and the expression levels of c-Fos protein in hippocampus were detected by immunohistochemistry. Result:Compared with the normal group， the SD mice in the model group were in a poorer general state and severe fatigue was observed. Compared with the model group， SD mice in each dose group of Shengyutang got improved in eating， activity， sleep， hair color， and response to external stimuli. Compared with the normal group， the body weight of SD mice in the model group was significantly reduced （<italic>P</italic><0.05）， but the body weight in the Shengyutang high-dose group increased the most as compared with the model group （<italic>P</italic><0.05）. Compared with the normal group， the hippocampal cells in the model group were disorderly arranged， incomplete in shape， increased in gap and decreased in number. Compared with the model group， the number of neurons in the hippocampus of SD mice in each dose group of Shengyutang increased. Compared with the normal group， the escape latency time of SD mice in the model group was significantly prolonged， the times of crossing platform and the residence time in the target quadrant significantly decreased （<italic>P</italic><0.01）. Compared with the model group， the times of crossing platform and the residence time in the target quadrant of mice in each dose group of Shengyutang significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the normal group， the levels of 5-HT， 5-HIAA， <italic>L</italic>-DOPA， DOPAC， EP， NE， HVA and DA in the model group significantly decreased （<italic>P</italic><0.05，<italic> P</italic><0.01）； but these levels in each dose group of Shengyutang were higher than those in model group （<italic>P</italic><0.05）. Compared with the normal group， the average MD value of c-Fos protein in the hippocampus of the model group significantly increased （<italic>P</italic><0.01）， and the expression levels of c-Fos protein in the hippocampus of Shengyutang groups were significantly lower than those in model group （<italic>P</italic><0.01）. Conclusion:Shengyutang can improve the learning and memory abilities of SD rats， and its mechanism may be related to the decrease of monoamine neurotransmitter and c-Fos protein expression.

Traditional Chinese Medicine Regulates Notch Signaling Pathway to Prevent and Treat Renal Diseases：A Review / 中国实验方剂学杂志

As common and frequently-occurring disorders in clinic practice，renal diseases are characterized by the impairment of kidney structure and function due to a variety of reasons and can be divided into primary，secondary， and hereditary types. Clinically，the impairment of kidney structure and function is usually a chronic progressive process，and the resulting chronic renal diseases have become a major public health problem endangering human health worldwide. Notch signaling pathway affects cell proliferation，differentiation，migration，growth， and apoptosis and determines the fate of cells. Abnormal expression or gene mutation of Notch will cause tissue damage， followed by the occurrence and development of a variety of renal diseases. Traditional Chinese medicine （TCM）， as an important means to prevent and treat renal diseases，has the characteristics of acting on multiple targets and signaling pathways with multiple components，and is often used as a routine or potential complementary therapy for the treatment of chronic renal diseases and also a source of new drug discovery. In recent years， considering the limitations of western medicine in treating renal diseases，more and more scholars have begun to take Notch signaling pathway as the breakthrough point for exploring TCM prevention and treatment of renal diseases. They have conducted clinical and experimental studies on the regulation of Notch signaling pathway by a variety of individual Chinese herbs or their extracts，Chinese patent medicines， and Chinese medicinal compounds，and found that TCM exerted the renal protective effects by inhibiting the Notch signaling pathway. By collecting relevant literatures on TCM prevention and treatment of various renal diseases，especially those concerning TCM regulation of Notch signaling pathway for preventing and treating such chronic renal diseases as diabetic nephropathy，immunoglobulin A （IgA） nephropathy，renal fibrosis，membranous nephropathy，focal segmental glomerulosclerosis， and renal cell carcinoma，this paper summarized the current research status，in order to provide reference for clinical prevention and treatment of various renal diseases and build up the factual basis for the universal application of TCM.

Research and verification of quality evaluation method of Epimedii Folium based on quantitative analysis of multi-components by single marker / 中国中药杂志

The quality control of Epimedii Folium, composed of diverse constituents, is single at present. In view of this, an eva-luation method of 13 chemical constituents based on quantitative analysis of multi-components by single marker(QAMS) was established to further explore the composition differences of raw products and alcohol extracts in different batches and the influence of alcohol extraction on the composition, so as to provide a reference for improving the quality evaluation and control of Epimedii Folium. The fingerprints of different batches of Epimedii Folium were constructed by ultra-high performance liquid chromatography(UPLC) to evaluate the inter-batch consistency. The changes of the flavonoids in Epimedii Folium during alcohol extraction were analyzed based on determined levels and heat map, and the reasons for the changes were preliminarily discussed. With icariin, the quality control component recorded in the Chinese Pharmacopoeia, as the internal reference, the stability of the relative correction factors of chemical components under different conditions was investigated to obtain the relative correction factors. Then the determination results of QAMS and the external standard method were compared to verify the accuracy of QAMS. The results revealed that all batches of Epimedii Folium met the requirements specified in the Chinese Pharmacopoeia, and the fingerprints of Epimedii Folium from the same place of origin exhibited a high similarity. Raw products and alcohol extracts of Epimedii Folium could be clearly distinguished by prenylated flavonoids, which are potential biomarkers for quality control. Additionally, the glycoside hydrolysis in the alcohol extraction was preliminarily explored. The QAMS method has good accuracy, durability, and repeatability in determining 13 chemical components in Epimedii Folium under different experimental conditions. No significant difference in the results obtained by the two methods was observed. This study can provide a reference for comprehensive, rapid and reasonable quality evaluation of Epimedii Folium.

Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of insomnia / 中国中药杂志

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of insomnia by frequency network Meta-analysis. Randomized controlled trials of Chinese patent medicines for insomnia were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library databases from the time of database establishment to October 2020. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 11 kinds of Chinese patent medicines in 27 RCTs were included. According to Meta-analysis, in term of the effective rate, Tianmeng Liquid, Zaoren Anshen Capsules, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Anshen Bunao Liquid and Qiye Anshen Tablets combined with nonbenzodiazepine drugs(NBZDs) were superior to NBZDs alone. In term of the improvement of Pittsburg sleeping quality index(PSQI) score, Tianmeng Liquid, Shumian Capsules, Shensong Yangxin Capsules, Bailemian Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Yangxue Qingnao Granules and Yindan Xinnaotong Capsules combined with NBZDs were superior to NBZDs alone. In terms of the safety, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets and Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. In terms of the avoidance of dizziness and headache, Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. The results of Network Meta-analysis indicated that in term of the effective rate, top three optimal medication regimens were NBZDs combined with Shugan Jieyu Capsules, combined with Zaoren Anshen Capsules and combined with Shensong Yangxin Capsules in the order from high to low. With the respect of improvement of PSQI score, top three optimal medication regimens were NBZDs combined with Yangxue Qingnao Granules, combined with Tianmeng Liquid and combined with Yindan Xinnaotong Capsules in the order from high to low. In terms of the safety, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Shensong Yangxin Capsules and combined with Shenqi Wuweizi Tablets in the order from high to low. In terms of the avoidance of dizziness and headache, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Zaoren Anshen Capsules and combined with Shumian Capsules in the order from high to low. In terms of the avoidance of fatigue, top three optimal medication regimens were NBZDs combined with Shensong Yangxin Capsules, combined with Shumian Capsules and combined with Qiye Anshen Tablets in the order from high to low. In conclusion, Chinese patent medicines combined with NBZDs can effectively alleviate the symptoms of insomnia with a high safety. However, the conclusion of this study needs to be verified by more high-quality studies because of the low methodological quality of the included studies.

Effects of Human Immunodeficiency Virus-positive Mothers Receiving Antiretroviral Therapy to Prevent Mother-to-child Transmission on the Growth and Development of 18-month-old Children in Lingshan County of Guangxi / 中国医学科学院学报

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(

Anti-inflammatory target prediction of Gentianae Radix et Rhizoma based on network pharmacology and construction of a bioassay method for its quality control / 中国中药杂志

Based on the heat-clearing and detoxifying effects of Gentianae Radix et Rhizoma, the network pharmacology is mainly used to predict the potential targets of Gentianae Radix et Rhizoma for anti-inflammatory activity and to perform the experimental verification. A method for detecting the biological potency of Gentianae Radix et Rhizoma based on verifiable targets has been established to provide a reference for improving the quality evaluation and control standards of Gentianae Radix et Rhizoma. High performance liquid chromatography can be used to construct chemical fingerprints of different batches of Gentianae Radix et Rhizoma. Constructing a component-target-disease network of Gentianae Radix et Rhizoma for its anti-inflammatory activity was applied to screen potential anti-inflammatory components and related targets of Gentianae Radix et Rhizoma, and to verify the target of Gentianae Radix et Rhizoma by using biological evaluation methods. Detecting the biological potency of different batches of Gentianae Radix et Rhizoma extracts was used to inhibit COX-2 enzyme activity based the verifiable target cyclooxygenase-2(COX-2). The results showed that different batches of Gentianae Radix et Rhizoma accorded with the pharmacopoeia testing regulations, and the chemical fingerprints have a high similarity(similarity>0.93), suggesting that there is no significant difference in the characteristics of the chemical components. Based on network pharmacology predictions, 18 candidate targets were found to have potential direct interactions with the ingredients in Gentianae Radix et Rhizoma. Among them, the most important target is COX-2. Based on the experimental verification of recombinant human COX-2 protease activity inhibition, Gentianae Radix et Rhizoma can inhibit the COX-2 enzyme activity in a dose-dependent manner. It can function with a low concentration(0.75 mg·mL~(-1)), which preliminarily confirmed the accuracy of network pharmacology prediction. The biological potency detection method of Gentianae Radix et Rhizoma based on COX-2 inhibitory activity was optimized and established. The qualitative response parallel line method was used to calculate the biological potency of anti-inflammatory activity, which ranged from 23.04 to 46.60 U·mg~(-1). For network pharmacology prediction, it can screen and clarify the possible targets of traditional Chinese medicine rapidly, which can guide the establishment of a biological evaluation method for the quality of medicinal materials with related activities. Compared with chemical fingerprints, the biological potency testing can better detect quality fluctuations of traditional Chinese medicine.