Molecular dynamics simulation of hybrid structure and mechanical properties of DLC/Ni-DLC thin films.

To improve the mechanical properties of the rolling body surface of wind power bearings, extend its service life. In this study, a large-scale molecular/atomic parallel processor LAMMPS was introduced, and then the process of magnetron sputtering technology in the preparation of DLC/Ni-DLC thin films on the 42CrMo substrate material was simulated. The effects of deposition parameters such as sputtering temperature, sputtering voltage, deposition air pressure, and Ni doping on the residual stress, film base bonding, and organizational structure of the thin films were investigated. The simulation results show that for different deposition parameters, the atomic tensile and compressive stresses existed simultaneously in DLC/Ni-DLC films, and the residual stresses were between - 0.504-5.003 Gpa and - 2.11-0.065 Gpa, respectively; the doping of Ni effectively improved the distribution of hybrid structure and the mechanical properties of the DLC films, and the ratio of the sp3 hybrid structure in the film organization was about 2.56 times higher than that of the non-doped films, and the membrane base bonding force was increased by 32.78% and the residual stress is reduced and transitioned from tensile stress to compressive stress. In addition, it was observed that the thickness of the mixed layer of DLC/Ni-DLC films with the substrate was not increased after the thickness of the mixed layer was extended to about 2 nm. Nickel doping and reasonable control of deposition parameters help to reduce the residual stress and improve the bonding strength of the film by changing the organizational structure of the film, which provides an important theoretical and scientific basis for the preparation of low-stress, high-performance and long-life DLC films and the wide application of rolling bodies for wind power bearings under complex working conditions.

Pathological Mechanism of Diabetes Based on NF-κB Signaling Pathway and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

As people's living standards improve， the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B （NF-κB） in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors， so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer， and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine （TCM） treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad， it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation， oxidative stress， and energy metabolism， and it is involved in mediating inflammation， pancreatic β cell apoptosis， insulin signal transduction， and other physiological functions. Therefore， blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present， Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections， but the adverse reactions are obvious. TCM has been characterized by multi-target， extensive action， and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation， regulating qi and eliminating phlegm， clearing heat and detoxifying， and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper， the association between NF-κB signaling pathway and diabetes was summarized， and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed， so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.

Role of CIP2A in preoperative sleep deprivation-induced aggravation of postoperative cognitive dysfunction in aged mice / 中华麻醉学杂志

Objective:To evaluate the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in preoperative sleep deprivation (PSD)-induced aggravation of postoperative cognitive dysfunction (POCD) in aged mice.Methods:One hundred and ten healthy C57BL/6J mice of either sex, aged 18-20 months, weighing 29-35 g, were divided into 5 groups ( n=22 each) using a random number table method: sham operation group (S group), abdominal surgery group (O group), PSD + abdominal surgery group (D+ O group), CIP2A shRNA + abdominal surgery group (CS+ O group), and CIP2A shRNA+ PSD+ abdominal surgery group (CS+ D+ O group). At 14 days before surgery, control shRNA lentivirus was injected into the hippocampus in S, O and CS+ O groups, and CIP2A shRNA was injected into the hippocampus in D+ O and CS+ D+ O groups. PSD was carried out for 3 consecutive days prior to surgery. Cognitive function was assessed using the Morris water maze test at days 7-11 after surgery. The mice were sacrificed under deep anesthesia at day 3 after surgery, and hippocampal tissues were obtained to determine the expression of CIP2A, high mobility group box 1 (HMGB1), ionized calcium-binding adapter molecule 1 (Iba-1), alpha subunit of protein phosphatase 2A (PP2Aa), catalytic subunit of protein phosphatase 2A (PP2Ac), phosphorylated tau protein (p-tau) (S396), and p-tau (S404) (by Western blot), levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD), and count of Iba-1 positive cells in the hippocampal CA1 region (using immunofluorescence staining). Results:Compared with S group, the escape latency was significantly prolonged, the frequency of crossing the platform was reduced, duration of stay in the target quadrant was shortened, the expression of CIP2A, Iba-1 and HMGB1 was up-regulated, PP2Ac expression was down-regulated, levels of ROS and MDA and count of Iba-1 positive cells were increased, and the activity of SOD was decreased in O group ( P<0.05). Compared with O group, the escape latency was significantly prolonged, the frequency of crossing the platform was reduced, duration of stay in the target quadrant was shortened, the expression of CIP2A, Iba-1 and HMGB1 was up-regulated, PP2Ac expression was down-regulated, levels of ROS and MDA and count of Iba-1 positive cells were increased, and the activity of SOD was decreased in D+ O group, and the escape latency was significantly shortened, the frequency of crossing the platform was increased, duration of stay in the target quadrant was prolonged, the expression of CIP2A, Iba-1 and HMGB1 was down-regulated, PP2Ac expression was up-regulated, levels of ROS and MDA and count of Iba-1 positive cells were decreased, and the activity of SOD was increased in CS+ O group ( P<0.05). Compared with D+ O group, the escape latency was significantly shortened, the frequency of crossing the platform was increased, duration of stay in the target quadrant was prolonged, the expression of CIP2A, Iba-1 and HMGB1 was down-regulated, PP2Ac expression was up-regulated, levels of ROS and MDA and count of Iba-1 positive cells were decreased, and the activity of SOD was increased in CS+ D+ O group ( P<0.05). There was no significant difference in PP2Aa expression among the five groups ( P>0.05). Conclusions:The mechanism by which PSD aggravates POCD is related to up-regulating the expression of CIP2A and promoting oxidative stress responses, neuroinflammatory responses and phosphorylation of tau protein in aged mice.

Effect of ethyl acetate extract from Mimosa pudica root on acute myeloid leukemia in mice / 中国药房

OBJECTIVE To study the inhibitory effect of ethyl acetate extract from Mimosa pudica root （ethyl acetate extract for short） on acute myeloid leukemia in mice. METHODS Different concentrations of ethyl acetate extract （0.062 5， 0.125， 0.25， 0.5 mg/mL） were used to treat acute myelomonocytic leukemia cell lines WEHI-3， and their effects on cell viability were investigated. Fifty BALB/C mice were randomly divided into blank control group， model group， positive control group （5- fluorouracil， 13 mg/kg）， and ethyl acetate extract low-dose and high-dose groups （50， 200 mg/kg）， with 10 mice in each group. Except for the blank control group， the leukemia model was constructed by intraperitoneal injection of WEHI-3 cells in other groups， and from the second day of modeling， corresponding drugs/water were orally administered once a day for 14 consecutive days. After the last administration， the liver and spleen indexes of mice were measured， and liver tissue pathological morphology observation， hematological analysis， and white blood cell differentiation detection were performed； the levels of cytokine [interleukin-2 （IL-2）， IL-3， interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）] in serum were determined； the levels of leukocyte surface markers [cluster of differentiation 3 （CD3）， CD19， CD11b， CD107b （Mac-3）] in whole blood were all detected. RESULTS After treated with 0.062 5-0.5 mg/mL ethyl acetate， the inhibition rate of cell proliferation were increased significantly （P＜0.05）. After intervention with high-dose ethyl acetate， the liver and spleen index， serum level of TNF-α， the levels of CD11b and Mac-3 in blood were significantly reduced （P＜0.05）， while serum levels of IL-2， IL-3 and IFN-γ， and the levels of CD3 and CD19 in blood were increased significantly （P＜0.05）. Occasional lymphocyte infiltration was present in the liver parenchyma， with almost no infiltration of inflammatory cells； hematology improvement and weakened white blood cell differentiation were found. CONCLUSIONS The ethyl acetate extract of M. pudica root can inhibit the proliferation of WEHI-cells， and improve symptoms in acute myeloid leukemia mice， the mechanism of which may be associated with enhancing the immune function.

Effect of ethyl acetate extract from Mimosa pudica root on acute myeloid leukemia in mice / 中国药房

OBJECTIVE To study the inhibitory effect of ethyl acetate extract from Mimosa pudica root （ethyl acetate extract for short） on acute myeloid leukemia in mice. METHODS Different concentrations of ethyl acetate extract （0.062 5， 0.125， 0.25， 0.5 mg/mL） were used to treat acute myelomonocytic leukemia cell lines WEHI-3， and their effects on cell viability were investigated. Fifty BALB/C mice were randomly divided into blank control group， model group， positive control group （5- fluorouracil， 13 mg/kg）， and ethyl acetate extract low-dose and high-dose groups （50， 200 mg/kg）， with 10 mice in each group. Except for the blank control group， the leukemia model was constructed by intraperitoneal injection of WEHI-3 cells in other groups， and from the second day of modeling， corresponding drugs/water were orally administered once a day for 14 consecutive days. After the last administration， the liver and spleen indexes of mice were measured， and liver tissue pathological morphology observation， hematological analysis， and white blood cell differentiation detection were performed； the levels of cytokine [interleukin-2 （IL-2）， IL-3， interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）] in serum were determined； the levels of leukocyte surface markers [cluster of differentiation 3 （CD3）， CD19， CD11b， CD107b （Mac-3）] in whole blood were all detected. RESULTS After treated with 0.062 5-0.5 mg/mL ethyl acetate， the inhibition rate of cell proliferation were increased significantly （P＜0.05）. After intervention with high-dose ethyl acetate， the liver and spleen index， serum level of TNF-α， the levels of CD11b and Mac-3 in blood were significantly reduced （P＜0.05）， while serum levels of IL-2， IL-3 and IFN-γ， and the levels of CD3 and CD19 in blood were increased significantly （P＜0.05）. Occasional lymphocyte infiltration was present in the liver parenchyma， with almost no infiltration of inflammatory cells； hematology improvement and weakened white blood cell differentiation were found. CONCLUSIONS The ethyl acetate extract of M. pudica root can inhibit the proliferation of WEHI-cells， and improve symptoms in acute myeloid leukemia mice， the mechanism of which may be associated with enhancing the immune function.

Imaging diagnosis reasoning and countermeasures of pulmonary ground-glass nodules / 中国综合临床

The pulmonary ground glass nodule (GGN) is a common clinical phenomenon at present, and most of them are tumors. The new classification classifies these neoplastic lesions into pre invasive lesions and invasive adenocarcinoma, and proposes micro invasive carcinoma separately, because the cure rate of surgical resection is almost 100%. Computed tomography (CT) is the first choice for preoperative examination, especially the ultra-high resolution target scanning assisted by physiological ventilation can better display the characteristics of GGN. On this basis, it can effectively determine the aggressiveness of GGN, which is worth recommended.

Clinical significance of next-generation sequencing-based IGH/IGK gene rearrangement analysis in the diagnosis of minimal residual disease of children with acute B-cell lymphoblastic leukemia / 中华实用儿科临床杂志

Objective:To assess the clinical significance of next-generation sequencing (NGS)-based IGH/ IGK gene rearrangement analysis versus flow cytometry (FCM) in diagnosing minimal residual disease (MRD) of children with acute B-cell lymphoblastic leukemia (B-ALL). Methods:Clinical data, NGS-MRD and FCM-MRD findings at the initial diagnosis and after induction chemotherapy of 85 children diagnosed as B-ALL in Children′s Hospital of Nanjing Medical University from July 2019 to July 2021, were retrospectively analyzed.The sensitivity of the two methods, and the positive rate were compared by χ2 test or Fisher′ s test.The correlation was identified by Spearman correlation analysis. Results:Dominant clone sequences were detected in all children at the initial diagnosis by NGS, while selection markers were identified by FCM in 75(88.2%) patients.Positive MRD rate detected by NGS-MRD was significantly higher than that of FCM-MRD at the same time point after induction chemotherapy[31.8%(27/85) vs.9.4%(8/85), P<0.001]. Compared with those of FCM-MRD, NGS-MRD had good sensitivity (100.0%), specificity (75.3%) and negative predictive value (100.0%), and the positive predictive value was 29.6%.MRD results detected by NGS were consistent with that of FCM ( r=0.569, P<0.001). By July 27, 2022, 2 patients with NGS-MRD (+ )FCM-MRD (-)relapsed during maintenance chemotherapy. Conclusions:NGS is highly consistent with FCM in the detection of MRD in children with B-ALL, which is more sensitive.The combination of NGS-MRD and FCM-MRD benefits more in monitoring MRD in children with B-ALL after induction chemotherapy.

Efficacy and safety of sofosbuvir-based direct-acting antiviral treatment in children and adolescent patients with chronic hepatitis C / 中华传染病杂志

Objective:To explore the efficacy and safety of sofosbuvir-based direct-acting antiviral treatment in children and adolescent patients with chronic hepatitis C (CHC).Methods:A total of 52 children and adolescent patients who admitted to The Third People′s Hospital of Kunming City and The People′s Hospital of Fuyuan County aged from three to 17 years old with CHC from January 2018 to August 2022 were enrolled, and their basic information was collected. Patients were treated with sofosbuvir/velpatasvir (SOF/VEL) or ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin for 12 weeks. The biochemical and virological indexes were followed up before and after treatment and 12 weeks after withdrawal. The primary endpoint was the sustained virological response (SVR) at week 12 of follow-up after treatment, and the occurrence of adverse events (AE) during treatment. Statistical analysis was used by nonparametric test.Results:A total of 52 patients with CHC including 38 children and 14 adolescents were enrolled. Thirty-one were male and 21 were female. The age was 9(7, 12) years old. Among 52 patients, seven patients were type 1b, 11 were type 2a, three were type 2, five were type 3a, 18 were type 3b, one was type 6a, three were type 6k, four were type 6n and one was type 6v. Twelve (23.1%) patients were vertical transmission, 21(40.4%) patients had horizontal transmission among family members, two (3.8%) patients were blood fluid transmission, and 17(32.7%) were unknown transmission route. Compared with the baseline levels, Total bilirubin, alanine aminotransferase and aspartate aminotransferase were all significantly decreased after 12 weeks of treatment and 12 weeks after withdrawal, and the differences were statistically significant ( F=12.71, 30.23 and 42.52, respectively, all P<0.05). Up to September 30, 2022, 100.0%(52/52) of patients achieved SVR at the end of treatment. For patients who completed follow-up for 12 weeks after treatment, 95.8%(46/48) achieved SVR. Common AEs during treatment were fatigue (11.5%(6/52)), headache (5.8%(3/52)), dizziness (1.9%(1/52)), abdominal pain (3.8%(2/52)), diarrhea (1.9%(1/52)), rash (1.9%(1/52)) and skin pruritus (1.9%(1/52)). No patients discontinued treatment because of AE. Conclusions:Sofosbuvir-based direct-acting antiviral treatment is efficient and well-tolerated in children and adolescent patients with CHC. No patients discontinued treatment due to AE.

Comparison of the detection rates of preconception health risks among Chinese couples of reproductive age in 2013 and 2019 / 中华健康管理学杂志

Objective:To assess the detection rates of preconception health risks among couples of reproductive age in China and analyze the differences between 2013 and 2019.Methods:In this cross-sectional study, the preconception health examination data of 9 153 916 couples of 20-49 years who participated in the National Free Preconception Health Examination Project in 2013 or 2019 were consecutively selected. The health risks involved eight aspects in women (genetic risk, reproductive risk, chronic disease risk, infectious risk, nutritional risk, behavioral risk, environmental risk and psychosocial risk) and seven aspects in men except for reproductive risks were assessed. The t test and χ2 test were used to compare the differences in demographic characteristics between the couples of reproductive age. The detection rates and 95% CI of each preconception health risk were calculated and the χ2 test was used to compare the differences in the detection rates of risk factors. Results:In 2019, the proportion of couples of reproductive age in China who were 35 years or older, had an education background of high school and above, workers, and held non-agricultural registered residence were all higher than those in 2013 (15.18% vs 6.22%, 52.12% vs 29.78%, 8.33% vs 7.17%, 12.39% vs 6.64%), while the proportion of farmers was significantly lower than that in 2013 (60.95% vs 76.87%) (all P<0.001). In 2013, the three health risks with the highest detection rate among Chinese women of reproductive age was nutritional risk (37.50%), infectious risk (16.95%) and psychosocial risk (11.62%), respectively; while in 2019, it was nutritional risk (38.07%), infectious risk (12.82%), and chronic disease risk (11.12%), respectively. The detection rate of nutritional risk in Chinese women of reproductive age in 2019 was significantly higher than that in 2013 (38.07% vs 37.50%), while the detection rates of infectious risk and psychosocial risk were both lower than those in 2013 (12.82% vs 16.95% and 7.37% vs 11.62%) (all P<0.001). In 2013, the top three risks detected in men of reproductive age was behavioral risk (44.87%), nutritional risk (36.81%) and psychosocial risk (13.43%), respectively; and in 2019, it was nutritional risk (45.47%), behavioral risk (38.76%) and psychosocial risk (9.18%), respectively. The detection rates of nutritional risk in men of reproductive age in 2019 was significantly higher than that in 2013 (45.47% vs 36.81%), while the detection rates of behavioral risk and psychosocial risk were both lower than those in 2013 (38.76% vs 44.87%, 9.18% vs 13.43%) (all P<0.001). Conclusions:The detection rate of nutritional risk in couples of reproductive age and genetic risk in men in 2019 in China are higher than those in 2013, and the exposure to the other preconception health risks is decreasing. The nutritional risk, infection risk, psychosocial risk and chronic disease risk are the main risk factors for women of reproductive age, while the nutritional risk, behavioral risk and psychosocial risk are the main risk factors for men.

Research progress on multiplexed point-of-care testing technology for the diagnosis of infectious diseases / 中华检验医学杂志

Accurate and rapid diagnosis of infectious diseases can effectively prevent their spread and promptly curb the epidemic hazards. Multiplexed point-of-care testing (x-POCT) technology can effectively avoid misdiagnosis caused by the detection of one single target and achieve rapid screening and timely control of multiple infectious diseases. Research progress and the latest applications of x-POCT including x-POCT assay methods for different targets in the diagnosis of infectious diseases and their pathogens are summarized in this review. The paper-based, microfluidic chip-based, and microdroplet-based device platforms of x-POCT, and eventually the challenges and future perspectives of x-POCT, especially progress on the effective infectious disease surveillance network establishment under One Health concept are highlighted.

Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway / 中国天然药物

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.

Rutin Promotes Browning of 3T3-L1 Preadipocytes and Its Mechanism / 中国实验方剂学杂志

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

Chinese Medicine Monomers Against Pancreatic Cancer： A Review / 中国实验方剂学杂志

Pancreatic cancer is a disease with a high fatality rate， with a five-year survival rate of no more than 10% and a significantly increasing annual mortality rate. The common pathogenesis factors of pancreatic cancer are family inheritance， diet， pancreatitis， obesity， etc.， among which， family inheritance of pancreatic cancer is the main reason， and about 7%-10% of patients have family inheritance. Surgery is an effective way to treat pancreatic cancer in patients and improve their survival， but most people are diagnosed with pancreatic cancer at intermediate and advanced stages and lose the opportunity for surgical treatment. Therefore， radiotherapy， interventional therapy， supportive treatment， immunotherapy， and other treatments are used clinically to relieve symptoms and prolong the survival of patients. The commonly used clinical drug is gemcitabine. Although it can inhibit tumor growth and improve the condition， it can bring side effects such as bone marrow suppression， rash， digestive tract side effects， and drug resistance. The damage of these side effects to the human body is systemic. Chinese medicine can be used alone or in combination with other treatment methods to reduce the toxic and side effects of chemotherapy， restore the physical energy of patients， and reduce its related complications. Chinese medicine contains a large number of active ingredients， including alkaloids， flavonoids， saponins， phenolic acids， and organic acids， with anti-inflammatory， anti-viral， anti-tumor， and other curative effects. Many clinical studies of traditional Chinese medicine （TCM） on cancers have verified that TCM plays a positive role in tumor prevention and treatment， especially in improving and controlling clinical symptoms， and also plays a good detoxification effect on radiotherapy and chemotherapy， with good results achieved in improving bone marrow suppression， improving immunity， improving quality of life， and prolonging survival. This paper reviewed the anti-pancreatic cancer mechanism of Chinese medicine monomers based on literature in China and abroad， aiming to provide new potential drug candidates for the treatment of pancreatic cancer.

Analysis and prospects of a new component circular RNA in breast milk / 中华实用儿科临床杂志

Breast milk contains a variety of bioactive components, which play a vital role in disease prevention and treatment.Among them, circular RNA(circRNA), which is a closed ring structure formed by covalent bonds, has aroused interest because of its conservation and stability.Pediatric researchers should attach importance to studies on circRNA in breast milk, as they may bring new inspiration for breast milk functions.In this article, characteristics and functions of circRNA in breast milk will be investigated, and its research and prospects will be discussed.

Influencing factors for liver inflammation and fibrosis in the immune-tolerant phase of HBV infection / 临床肝胆病杂志

Objective To evaluate the degree of liver injury and liver fibrosis in patients in the immune-tolerant phase of chronic HBV infection, and to provide a basis for judging the condition of patients in the immune-tolerant phase. Methods A total of 300 patients with HBV DNA ≥10 7 IU/mL, alanine aminotransferase (ALT) ≤40 U/L, and complete data who were treated in The Third People's Hospital of Kunming from January 2015 to December 2019 were enrolled as subjects, and related data were collected, including age, sex, duration of HBV infection, blood biochemistry, hepatitis B surface antigen (HBsAg) level, and HBV DNA. Liver pathological examination was performed for all patients, and the patients were divided into G < 2 and G ≥2 groups according to inflammation grade and S < 2 and S ≥2 groups according to the degree of fibrosis. The t -test was used for comparison of continuous data between two groups, and univariate and multivariate unconditional logistic regression analyses were used to investigate the influencing factors for G ≥2 liver inflammation and S ≥2 liver fibrosis. Results Among the 300 patients, 213 (71%) had G ≥2 liver inflammation and 120 (40%) had S ≥2 liver fibrosis, with a baseline age of 26.06±9.01 years; male patients accounted for 48%, and the duration of infection was 5.62±5.09 years. The univariate analysis showed that there were significant differences between the G < 2 and G ≥2 groups in ALT, alkaline phosphatase (ALP), albumin (Alb), platelet count (PLT), diameter of the portal vein, and spleen thickness ( t =-26.677, -11.612, 2.149, 5.410, -6.092, and -2.911, all P < 0.05), and there were significant differences between the S < 2 and S ≥2 groups in duration of infection, ALT, ALP, Alb, HBV DNA, PLT, diameter of the portal vein, and spleen thickness ( t =-6.320, -6.694, -7.880, 2.349, 4.552, 19.160, -5.782, and -5.622, all P < 0.05). The multivariate analysis showed that ALT (odds ratio [ OR ]=10.270, 95% confidence interval [ CI ]: 2.212-47.672, P =0.003) and ALP ( OR =1.097, 95% CI : 1.013-1.188, P =0.023) were independent risk factors for G ≥2 liver inflammation in patients in the immune-tolerant phase, and ALP ( OR =1.034, 95% CI : 1.015-1.054, P < 0.001), PLT ( OR =0.913, 95% CI : 0.886-0.938, P < 0.001), HBV DNA ( OR =0.198, 95% CI : 0.062-0.636, P =0.007), and duration of infection ( OR =1.176, 95% CI : 1.033-1.340, P =0.015) were independent influencing factors for S ≥2 liver fibrosis in patients in the immune-tolerant phase. Conclusion Most patients in the immune-tolerant phase have significant liver histological changes. ALT and ALP are the influencing factors for significant liver inflammation, and ALP, HBV-DNA, PLT, and infection time are the influencing factors for significant liver fibrosis in patients in the immune-tolerant phase.

TGF-β-related Signaling Pathways in Pathogenesis of Diabetes and Prospect of Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

The incidence of diabetes has been on the rise as the result of lifestyle changes， especially the high-fat diet and reduced exercise. Thus， it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β （TGF-β） signaling pathways with diabetes complications and tumors， but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors， directly or indirectly leading to the apoptosis of islet β cells and insulin resistance （IR）， and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase （AMPK）， protooncogene （c-Myc）， Ski-relatednovel protein N （SnoN）， Smad ubiquitination regulatory factor 1 （Smurf1）， miR-335-5p， and other signaling molecules. They participate in the occurrence and development of IR， apoptosis of islet β cells， insulin secretion disorder， fibrosis of adipocytes， and metabolic disorder of adipocytes， and inhibit the browning of white adipose tissue， playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine （TCM）， the pathogenesis of diabetes is the deficiency of Qi and Yin， and the late stage is characterized by the syndrome of Qi deficiency， and Yang deficiency and blood stasis， which should be treated according to the principle of replenishing Qi and nourishing Yin， warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways， elucidating the roles of them in pathogenesis of diabetes， and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.

Anemia in preschool children in China and its association with neuropsychological development / 中国学校卫生

Objective@#To explore the relationship between anemia and neuropsychological development in various domains among preschool children in China.@*Methods@#Data came from the National Nutrition and Health Systematic Survey for children in China, and 3 261 preschool children aged 2-6 years and their parents from 28 sites across 14 provinces were recruited in this study. Parental and child characteristics were obtained by interview administrated questionnaires. Blood hemoglobin(Hb) concentration was determined by Hemocue method. Neuropsychological development quotients were assessed using the Development Scale for Children Aged 0-6 Years(WS/T 580-2017).@*Results@#The average Hb level was (125.23±11.49)g/L and the overall anemia prevalence was 10.30% among preschool children. After adjusting the confounding factors(sex, age, ethnicity, region, feeding mode, maternal status during pregnancy, etc), developmental quotients of gross motor( β=-2.15, 95%CI =-3.89--0.41), fine motor( β=-2.46, 95%CI =-4.12--0.79), adaptive behavior( β=-2.59, 95%CI =-4.42--0.76), language( β=-3.65, 95%CI =-5.53--1.78), personal social behavior( β=-3.11, 95%CI =-4.94--1.28) and full scale( β=-2.79, 95%CI =-4.10--1.49) among children with anemia were significantly lower than non anemic infants( P <0.05).@*Conclusion@#Anemia was negatively associated with developmental quotient, as well as five domains of gross motor, fine motor, adaptive behavior, language, and personal social behavior in preschool children aged 2-6 years. It is suggested to carry out the work of anemia monitoring and intervention in preschool children to further improve their neuropsychological development.

Molecular Identification of Tibetan Codonopsis Plants Based on ITS2 and psbA-trnH Barcode / 中国实验方剂学杂志

ObjectiveTo identify the molecular biology of various species of Tibetan Codonopsis plants based on internal transcribed spacer（ITS）2 and psbA-trnH sequence barcode technology. MethodThe genomic DNA of 28 Tibetan Codonopsis plant samples from four species （Codonopsis canescens，C. foetens subsp. nervosa，C. pilosula， and C. thalictrifolia var. mollis） were extracted，and the ITS2 and psbA-trnH sequences were amplified and sequenced. The related sequences of 81 Tibetan Codonopsis plant samples belonging to 15 species were downloaded from GenBank， and MEGA 6.0 was used for sequence comparison and mutation site analysis. The GC content and genetic distance within and between species were calculated. Additionally， phylogenetic trees were constructed by maximum likelihood （ML） method， neighbor-joining （NJ） method，and unweighted pair-group method with arithmetic means （UPGMA） . ResultAccording to the mutation site，C. canescens， C. pilosula，C. pilosula subsp. tangshen， C. pilosula var. modesta，C. bhutanica，C. clematidea，C. lanceolata，C. subglobosa and C. foetens were distinguished. In the phylogenetic trees，the optimal clustering effects for ITS2 and psbA-trnH sequences were obtained using the ML method and the UPGMA method， respectively， and 12 species were effectively clustered. ConclusionITS2 and psbA-trnH sequences have a high identification rate for species of single origin，but there are still some limitations in identifying variants and original variants. This study provides basis for the identification of affinity relationship and clinical safety of Tibetan Codonopsis plants.

Meridian Tropism of Components in Bupleuri Radix Based on Nonalcoholic Steatohepatitis Model and Principal Component Analysis / 中国实验方剂学杂志

ObjectiveTo explore the meridian tropism of components in Bupleuri Radix （Chaihu， CH） based on the model of nonalcoholic steatohepatitis （NASH） and clarify the substance basis of the meridian tropism of CH in Xiaoyaosan （XYS） by means of principal component analysis. MethodEighty SPF male C57BL/6 mice were randomly assigned into 8 groups， with 10 mice in each group. Except that the blank group was fed with the methionine choline-sufficient （MCS） diet， the other mice were fed with methionine choline-deficient （MCD） diet for 4 weeks to establish the nonalcoholic steatohepatitis （NASH） model. After the established model was confirmed by hematoxylin-eosin （HE） staining， the mice were administrated with corresponding drugs by gavage once a day for 4 weeks. Specifically， the 8 groups were XYS group （2.874 g·kg-1）， XYS-CH group （2.445 g·kg-1）， XYS-CH+volatile oils （Vol， 0.163 mg·kg-1） group， XYS-CH+polysaccharides （Pol， 24.067 mg·kg-1） group， XYS-CH+flavones （Fla， 2.241 mg·kg-1） group， and XYS-CH+saponins （Sap， 2.746 mg·kg-1） group. The model group and the blank group were administrated with the same volume of normal saline. After the last administration， the mice were sacrificed for the collection of blood and liver tissue. The pathological changes of liver were observed by HE staining and oil red O staining. Enzyme linked immunosorbent assay （ELISA） kits were used to determine the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL） in serum as well as malondialdehyde （MDA）， superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in liver. SPSS Statistics 23 was used for principal component analysis and comprehensive evaluation to determine the substance basis of the meridian tropism of CH in NASH mice. ResultCompared with the blank control group， the modeling led to hepatocyte swelling， increased fat vacuoles， and appearance of inflammatory cells. Further， the modeling elevated the levels of ALT， AST， TG， TC， and LDL and lowered the HDL level in serum， and it increased the MDA level and decreased the SOD， CAT， and GSH-Px levels in liver. Compared with the model group， the administration of XYS and XYS-CH in combination with the components of CH alleviated the oxidative damage in liver （P<0.05）. The comprehensive score of the pharmacological efficacy was in a descending order as follows： XYS > XYS-CH+Sap > XYS-CH+Fla > XYS-CH+Pol > XYS-CH+Vol > XYS-CH. Among the chemical components of CH， Sap had the best effect. ConclusionSap lowers the blood lipid level， regulates the abnormal lipid metabolism， and alleviates the oxidative damage of liver， which is the substance basis for CH to exert the meridian tropism in liver.

Total Flavonoids of Mulberry Leaves Improves Liver Lipid Metabolism in Type 2 Diabetic Rats by Regulating PPAR-α/CPT-1 Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L-1 were divided into three administration groups with the high dose （300 mg·kg-1）， medium dose （150 mg·kg-1）， and low dose （75 mg·kg-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.