The biological principle of "Biao Ben Jian Zhi" / 药学学报

Along with the progress of pharmaceutical science in the past century, the theme of pharmacology has gone through pseudo agent scheme, to ligand-receptor model, and then to the theory of targeted therapy today. Due to the success of drug R&D, current drug research keeps its focus mainly on drugs with single target and precise treatment, in which the molecular mechanism is relatively clear but the therapeutic efficacy is often limited. Thus, there is a big space for exploration in the field of pharmacology. In the past 30 years, several novel chemical drugs, originated from traditional Chinese medicine, have been identified and then used in clinic, provoking a strong interest to explore new theory for pharmacology, of which the term of "Biao Ben Jian Zhi" (treating diseases by directing symptoms and root causes) has demonstrated a promising nature. We consider this concept useful for future drug discovery, drug design and clinical therapy. In this review, example drugs such as berberine, metformin and azvudine, are discussed, and "drug Cloud" (dCloud) model is introduced to elaborate the mechanism of treating diseases by directing symptoms and root causes of diseases.

Short chain fatty acid: a messenger of gut-organ axis for disease regulation / 药学学报

Gut microbiota is a complex and dynamic system, and is essential for the health of the body. As the "second genome" of the body, it can establish communication with the important organs by regulating intestinal nerves, gastrointestinal hormones, intestinal barrier, immunity and metabolism, thus affecting host′s physiological functions. Short chain fatty acid (SCFA), known as one important metabolite of intestinal microbiota, is regarded as a significant messenger of the gut-organ communication, due to its extensive regulation in the body′s immunity, metabolism, endocrine and signal transduction. In this review, we summarize the interaction between gut-liver/brain/kidney/lung axis and diseases, and focus on the role and mechanism of SCFA in the gut-organ communication, hoping to provide new ideas for the treatment of the related diseases.

Efficacy and Mechanism of Shenbai Jiedu Prescription Against Proliferation of HCT116 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism by which Shenbai Jiedu prescription （SBJDF） inhibits the proliferation of colorectal cancer （CRC） HCT116 cells. MethodAfter 48 h treatment of HCT116 cells with SBJDF （0， 0.25， 0.5， 1， 2， 4 g·L-1）， the viability of HCT116 cells were determined by methyl thiazolyl tetrazolium （MTT） colorimetry. Following the classification of cells into blank control group and SBJDF （1， 2， 4 g·L-1） groups， the effect of SBJDF on HCT116 cell morphology was observed under an inverted microscope. The effects of SBJDF on the proliferation of HCT116 cells and mitochondrial membrane potential （Δψm） were detected by colony formation assay and JC-1 probe， respectively. The flow cytometry was then performed for determining cell cycle distribution and apoptosis. The effects of SBJDF on cell cycle-， apoptosis-， and nuclear factor kappa-B （NF-κB） signaling pathway-related proteins were determined by Western blot. ResultSBJDF effectively inhibited the vitality of HCT116 cells and changed their morphology in a concentration-dependent manner. Compared with the blank control group， SBJDF at 1， 2， 4 g·L-1 significantly reduced cell colony formation （P<0.05， P<0.01），and SBJDF at 2 and 4 g·L-1 arrested the HCT116 cell cycle at G0/G1 phase （P<0.05， P<0.01）. Compared with the blank control group， SBJDF at 1， 2， 4 g·L-1 remarkably down-regulated the protein expression of CyclinD1 （P<0.05， P<0.01）. SBJDF at 2 and 4 g·L-1 lowered the CyclinA2 and cyclin-dependent kinase 4 （CDK4） （P<0.05， P<0.01）. SBJDF at 4 g·L-1 reduced the cyclin-dependent kinase 1 （CDK1） （P<0.01）. Compared with the blank control group， SBJDF at 2 and 4 g·L-1 induced HCT116 cell apoptosis， down-regulated the protein expression of anti-apoptosis-related proteins Bcl-2 and Bcl-xl as well as the NF-κB signaling pathway-related proteins IκB kinase α （IKKα），inhibitor α of NF-κB （IκBα），and phospho-NF-κB p65 （p-p65） （P<0.05， P<0.01）， and diminished the mitochondrial membrane potential of HCT116 cells. ConclusionSBJDF inhibits the proliferation of HCT116 cells， which may be related to its inhibition of the activation of NF-κB signaling pathway and the induction of cell cycle arrest and apoptosis.

Dengzhan Shengmai inhibits nonalcoholic fatty liver disease via regulating intestinal microenvironment / 药学学报

The aim of this study was to investigate the efficacy and mechanism of Dengzhan Shengmai (DZSM) against nonalcoholic fatty liver diseases (NAFLD). The animal experiment program was reviewed and approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The NAFLD model of Syrian golden hamsters was established by high fat diets. After 6 weeks of DZSM treatment, the serum lipid, hepatic lipid accumulation, liver function and inflammatory response were determined. The regulations of gut microbiota and short-chain fatty acids were detected by 16S rRNA gene sequencing and gas chromatography-mass spectrometry method, respectively. The gut barrier function was evaluated by enzyme linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot and histopathological methods and further verified in HepG2 cells. The results showed that the efficacy of DZSM against NAFLD was remarkably reduced after removal of the gut microbiota. The study of mechanism showed that DZSM significantly regulated the composition of gut microbiota, promoted the production and absorption of intestinal short-chain fatty acids, then leading to the reduction of hepatic lipid accumulation. Moreover, after DZSM treatment, the decreased lipopolysaccharide (LPS) level by improving the intestinal barrier function significantly inhibited the hepatic inflammation through down-regulating Toll like receptor 4 (TLR4)-nuclear factor kappa B (NFKB) signaling pathway. These results indicate that DZSM inhibits NAFLD via regulating intestinal microenvironment.

Comparison of suture anchor and simple suture for acute injury to lateral ankle ligament: mid-to long-term outcomes / 中华创伤骨科杂志

Objective:To compare the mid-to long-term clinical outcomes between suture anchor and simple suture for acute injury to lateral ankle ligament (cauda equina tear near the insertion).Methods:This retrospective study included 146 patients (professional and semi-professional athletes) who had been treated for acute injury to lateral ankle ligament (cauda equina tear near the insertion) at Department of Sports Medicine, The Third Hospital Affiliated to Peking University from June 2007 to May 2017.They were 101 males and 45 females, with an age of (27.1±10.3) years (from 12 to 62 years). Depending on ligament repair techniques, the patients were divided into a suture anchor group of 81 cases subjected to reconstruction of the torn ligament with a 1.8 mm suture anchor, and a simple suture group of 65 cases subjected to direct suture of the torn ligament with a braided thread. The 2 groups were compared in terms of visual analog scale (VAS) pain scores, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and Tegner scores at preoperation and the last follow-up, time and level of postoperative motion recovery, proportion of limited joint motion, incidence of re-sprain and patient satisfaction.Results:There was no significant difference in the preoperative general data between the 2 groups, showing they were comparable ( P>0.05). The mean follow-up duration was (46.1±14.1) months (from 36 to 132 months). The VAS pain score, AOFAS ankle-hindfoot score and Tegner score at the last follow-up were significantly improved than those before operation in all the patients ( P<0.05). Postoperatively, there was no significant difference between the 2 groups in VAS pain score, AOFAS ankle-hindfoot score, Tegner score, incidence of re-sprain or proportion of limited joint motion ( P> 0.05). The suture anchor group was significantly better than the simple suture group in the level of postoperative motion recovery (92%±13% versus 89%±13%) and time of postoperative motion recovery [(4.2±1.1) months versus (4.6±1.0) months] ( P<0.05). Conclusions:Ligament repair, either by suture anchor or by simple suture, is a reliable procedure for patients with high sports demands after severe acute injury to the lateral ankle ligament. Compared with simple suture, suture anchor may accelerate postoperative motion recovery to the pre-injury level.

Clinical efficacy of precise hepatectomy for the treatment of recurrent unilateral hepato-lithiasis and prognostic factors analysis / 中华消化外科杂志

Objective:To investigate the clinical efficacy of precise hepatectomy for the treatment of recurrent unilateral hepatolithiasis and prognostic factors.Methods:The retrospec-tive case-control study was conducted. The clinicopathological data of 166 patients with recurrent unilateral hepatolithiasis who were treated by precise hepatectomy in the First Affiliated Hospital of Anhui Medical University from January 2015 to January 2021 were collected. There were 51 males and 115 females, aged (58±12)years. Observation indicators: (1)diagnosis and classification; (2) surgical and intraoperative situations; (3) postoperative situations; (4) follow-up; (5) analysis of prognostic factors. Follow-up was conducted using the outpatient examination and telephone inter-view to detect final stone clearance or recurrence and survival of patients up to August 2021. Patients with T-tube were performed T-tube cholangiography or choledochoscopy to evaluate the final stone clearance rate at postoperative week 8. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. Univariate and multi-variate analyses were conducted using the Logistic regression model. Results:(1) Diagnosis and classifica-tion: 166 patients were diagnosed as hepatolithiasis by preoperative imaging examination and intraoperative evaluation, including 134 cases with common bile duct stones. Of the 166 patients, 115 cases had stones located in the left lobe of liver and 51 cases had stones located in the right lobe of liver. There were 111 cases with bile pigment stones, 31 cases with cholesterol stones, 24 cases with mixed type of stones. There were 9 cases classified as Tsunoda type Ⅰ, 89 cases as Tsunoda type Ⅱ, 65 cases as Tsunoda type Ⅲ, 3 cases as Tsunoda type Ⅳ. There were 12 cases classified as type Ⅰ, 99 cases as type Ⅱ, 47 cases as type Ⅲ, 8 cases as type Ⅳ according to Japanese classification in 2001. All the 166 patients were classified as type Ⅰ based on Chinese classification. According to the classification of author team, 166 patients were classified as type Ⅱ. (2) Surgical and intra-operative situations: 119 of 166 patients had liver lobe or segment atrophy. All the 166 patients underwent precise hepatectomy combined with different methods of drainage, of which 28 cases underwent left hemihepatectomy, 11 cases underwent right hemihepatectomy, 1 case underwent liver resection of segment Ⅰ, 5 cases underwent liver resection of segment Ⅱ, 5 cases underwent liver resection of segment Ⅲ, 8 cases underwent liver resection of segment Ⅳ (left medial lobe), 3 cases underwent liver resection of segment Ⅴ, 2 cases underwent liver resection of segment Ⅵ, 2 cases underwent liver resection of segment Ⅷ, 68 cases underwent liver resection of segment Ⅱ and Ⅲ (left lateral lobe), 3 cases underwent liver resection of segment Ⅴ and Ⅵ, 6 cases underwent liver resection of segment Ⅴ and Ⅷ (right anterior lobe), 21 cases underwent liver resection of segment Ⅵ and Ⅶ (right posterior lobe), 1 case underwent liver resection of segment Ⅱ, Ⅲ and Ⅳa, 1 case underwent liver resection of segment Ⅴ, Ⅵ and Ⅶ, 1 case underwent liver resection of segment Ⅰ, Ⅱ, Ⅲ and Ⅳ. For biliary drainage methods of 166 patients, 120 patients received T-tube external drainage, 23 cases received choledochojejunostomy, 23 cases received choledochojejunostomy combined with T-tube external drainage. The original cholangiojejunal anastomotic stenosis was found and reconstructed in 10 patients. The operation time was (258±87)minutes and intraopera-tive blood transfusion rate was 16.87%(28/166) of 166 patients. All the 166 patients underwent fiber choledochoscopy, showing 77 cases with normal function of Oddi sphincter, 38 cases with disorder, 40 cases with dysfunction. There were 11 patients undergoing choledochojejunostomy who were not evaluate the function of Oddi sphincter. There were 21.69%(36/166)of patients with intra-hepatic biliary stricture. One hundred and forty-nine of 166 patients were conducted bile culture, showing the positive rate as 75.17%(112/149). There were 22 cases cultured multiple kinds of bacteria. The most common bacterium was Escherichia coli (43 cases), followed by Pseudomonas aeruginosa (12 cases), Klebsiella pneumoniae (9 cases), Klebsiella oxytoca (7 cases), Enterococcus faecium (7 cases). (3) Postoperative situations. The postoperative complication rate of 166 patients was 16.87%(28/166). In the 8 patients with serious complications of Clavien-Dindo grade Ⅲ, 6 cases were performed thoracocentesis or abdominocentesis for effusion, 1 case was stopped bleeding under gastroscopy for stress ulcerbleeding, 1 case was performed surgery for adhesive intestinal obstruction. Two patients with septic shock of Clavien-Dindo grade Ⅳ were converted to intensive care unit for treatment and discharged after recovery. There were 13 patients with biliary leakage, 10 patients with pulmonary infection, 6 cases with incision infection, which were improved after conservative treatments. There was no perioperative death. The instant stone clearance rate of 166 patients was 81.93%(136/166). The duration of postoperative hospital stay of 166 patients was (11±6)days. (4) Follow-up: 166 patients were followed up for (37±17)months. The final stone clearance rate and stone recurrence rate of 166 patients were 94.58%(157/166) and 16.87%(28/166), respectively. According to Terblanche classification of prognosis, there were 91, 36, 25, 14 cases of grade Ⅰ, Ⅱ, Ⅲ, Ⅳ in 166 patients, respectively. Five of the 166 patients underwent intrahepatic secondary malignancy in which 4 cases died. (5) Analysis of prognostic factors: results of univariate analysis showed that biliary culture, the number of previous surgeries, immediate stone clearance, final stone clearance were related factors affecting the prognosis of precise hepatectomy in patients with recurrent unilateral hepatolithiasis ( odds ratio=2.29, 7.48, 2.69, 4.52, 95% confidence interval as 1.09?4.85, 2.80?19.93, 1.16?6.25, 1.15?17.77, P<0.05). Results of multivariate analysis showed that the number of previous surgeries ≥3 was an independent risk factor affecting the prognosis of precise hepatectomy in patients with recurrent unilateral hepato-lithiasis ( odds ratio=6.05, 95% confidence interval as 2.20?16.62, P<0.05). Conclusions:Precise hepatectomy is safe and effective for the treatment of patients with recurrent unilateral hepato-lithiasis. The number of previous surgeries ≥3 is an independent risk factor affecting the prognosis of precise hepatectomy in patients with recurren t unilateral hepatolithiasis.

Research progress of natural-derived compounds in the treatment of non-alcoholic fatty liver disease / 药学学报

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The prevalence of NAFLD is increasing year by year in the world, which seriously threaten the public health. The pathogenesis of NAFLD is complex, and there is no specific treatment for NAFLD. Natural-derived compounds have the characteristics of multi-target and multi-mechanism, which can improve the curative effect and reduce the toxic and side effects by regulating multiple factors of the disease. They are ideal drugs for treating complex diseases and have unique advantages in improving NAFLD. However, low intestinal absorption, poor bioavailability, and single medicine efficiency limit the utilization of many compounds, and further drug development and clinical application are challenging. This paper reviews the research progress of natural-derived compounds in the prevention and treatment of NAFLD in recent years, analyzes the existing problems, and discusses the improvement strategies, so as to provide reference for related research.

Progress of researches on schistosomiasis-associated pulmonary arterial hypertension / 中国血吸虫病防治杂志

Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is categorized as WHO Group I PAH because its clinical manifestations, laboratory and hemodynamic features share with PAH of other etiologies, such as idiopathic, heritable, HIV and autoimmune disorders. Sch-PAH is usually a life-threatening complication of hepatosplenic schistosomiasis characterized by changes in the vascular wall, remodeling and vasoconstriction with lesions primarily located in the precapillary segments of the pulmonary vasculature, which may result in a marked and sustained increase in pulmonary vascular resistance, right ventricular failure and ultimately death. Although egg deposition into lung and subsequent inflammatory cascades are key factors in the pathogenesis of Sch-PAH, the exact pathogenesis, course of disease and treatment of Sch-PAH remain largely uncertain. This review mainly discusses the pathophysiological and immunological mechanisms of Sch-PAH, so as to provide insights into the clinical diagnosis and treatment of Sch-PAH.

Inhibitory effect of Qing-Fei-Pai-Du decoction on coronavirus in vitro / 药学学报

Qing-Fei-Pai-Du decoction (QFPDD) is a combination of traditional Chinese medicine and plays an important role in the treatment of coronavirus disease 2019 (COVID-19). This study investigated the inhibitory effect of QFPDD on coronavirus replication and antiviral mechanism. The cytotoxicity of QFPDD was determined by PrestoBlue cell viability assay. Quantitive reverse transcription PCR (qRT-PCR) and immunofluorescence assay (IF) were used to detect the inhibitory effects of QFPDD on coronavirus at RNA and protein levels. qRT-PCR was used to detect the adsorption and penetration of coronavirus after QFPDD treatment. The effects of QFPDD on interferon (IFN) and interferon-stimulated genes (ISGs) were also detected by qRT-PCR. The results showed that QFPDD inhibited coronavirus at RNA and protein levels in a dose-dependent manner at non-toxic concentration, and QFPDD targeted in the early stages of coronavirus infection cycle. Preliminary mechanism studies have shown that QFPDD can directly block the virus entry into the cell by inhibiting virus adsorption, and QFPDD can also play an antiviral role by up-regulating the expression of IFN and ISGs. These results indicate QFPDD as a drug potential to treat coronavirus infection.

The anti-atherosclerotic effect and mechanism of puerarin / 药学学报

In recent years, with the improvement in living standards, the morbidity and mortality of cardiovascular and cerebrovascular diseases has increased markedly. Atherosclerosis is the main pathological basis for cardiovascular and cerebrovascular diseases, and there are many risk factors for atherosclerosis. The pharmacological effects of puerarin are broad, and considerable clinical data confirms that puerarin has a definite effect on cardiovascular diseases resulting from atherosclerosis. The use of puerarin for atherosclerosis has increased in recent years. This article reviews the effect and mechanism of puerarin on atherosclerosis.

Progress in diagnosis and treatment of meibomian gland dysfunction associated with dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

@#Considering the increased use of electronic devices, the incidence of dry eye disease(DED)has been rising. The condition has seriously affected people's work and lives. DED, the most common ocular surface disease, can be caused by many factors. The meibomian gland dysfunction(MGD)is one of the main factors. Either abnormal secretions from the meibomian gland or an obstruction of the gland ducts can lead to evaporative dry eye. By summarising the relevant literature, this review addresses the aetiology, pathology, diagnosis and treatment of DED associated with MGD.

Research progress on the interaction of neuropsychiatric drugs with the gut microbiota / 药学学报

The gut microbiota is an intricate and dynamic community composed of many symbiotic and pathogenic microorganisms, and works closely with the host. In recent years increasing evidence has supported the gut-brain axis theory, lending support for a link between gut microbiota and neuropsychiatric diseases. Since most of the drugs used to treat neuropsychiatric diseases enter the intestinal tract after oral administration, interaction with the gut microbiota is likely. A number of studies have shown that such drugs can change the composition and function of the gut microbiota. At the same time, the gut microbiota also participates in the metabolism of drugs, which in turn have beneficial or harmful effects on brain function. Therefore, the role of gut microbiota in drug metabolism also has attracted attention. This article reviews the research results of the interaction between the two, discusses the influence of neuropsychiatric diseases on the gut microbiota and the effect of the gut microbiota on psychoactive drugs, and provides new ideas for the treatment of various clinical neuropsychiatric diseases.

Chlorogenic acid down-regulates the expression of PD-L1 in esophageal squamous cell carcinoma via IFN-γ signaling pathway / 药学学报

In this study, the regulatory effects of chlorogenic acid (CGA) on the expression of programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC), as well as the role of interferon γ (IFN-γ), has been discussed using both in vitro and in vivo animal models. ESCC murine model was established according to the standard operating procedures (SOP) of Animal Experiment Center of Institute of Materia Medica, Chinese Academy of Medical Sciences. The expression of PD-L1 in esophageal tissues of murine models was analyzed using the microarray assay. Then, the results were verified by qRT-PCR, Western blot and immunohistochemistry (IHC) staining, the molecular mechanism was explored in KYSE180 and KYSE510 ESCC cells in vitro. The results showed that CGA could suppress the expression of PD-L1 in tumor tissues in murine models significantly, rather than the expression in KYSE180 and KYSE510 ESCC cells in vitro. However, after the pretreatment of IFN-γ, the expression of PD-L1 was significantly increased, then it was down-regulated by CGA in both dose- and time-dependent manner. Meanwhile, the expression of interferon regulatory factor 1 (IRF1), an upstream regulatory factor of PD-L1, was suppressed by CGA in both KYSE180 and KYSE510 pretreated with IFN-γ, which was consistent with the expression of PD-L1. These results indicate that CGA down-regulates the expression of PD-L1 in ESCC via IFN-γ-IRF1 signaling pathway, providing the molecular theoretical basis for exploration of new treatment of ESCC.

Characteristics and related factors of plantar pressure in the chronic ankle instability individuals / 北京大学学报(医学版)

OBJECTIVE@#To analyze characteristics and related factors of the plantar pressure during the level walking and single leg standing in the chronic ankle instability (CAI) individuals.@*METHODS@#From April 2019, 75 CAI individuals and 40 healthy individuals were enrolled in this study. Both of the static and dynamic plantar pressure were measured during six times level walking and three times single leg standing testing. The data including peak force, time to peak force in various foot contact areas and the time to boundary (TTB) and velocity of center of pressure (COP) were measured and compared between the affected side and the unaffected side and between the CAI cases and the healthy individuals. The correlations between the plantar pressure and the gender, Beighton score, affected side and body mass index (BMI) were analyzed.@*RESULTS@#The characteristics of plantar pressure distribution in the CAI individuals included: (1) During the level walking, the affected side showed the similar pressure contribution as the unaffected side (P>0.05). While compared with healthy individuals, there was a significantly higher peak force in the 5th metatarsal area (t=-3.86, P=0.03) of the affected side, lower peak force in the 1st (t=2.99, P=0.02), 2nd metatarsal head areas (t=2.09, P=0.01) of the affected side, medial hindfoot areas of both sides (affected, t=2.33, P=0.01; unaffected, t=3.74, P=0.02) and toes areass of both sides (affected, t=2.23, P=0.01; unaffected, t=3.28, P=0.02) and a delay to peak force in the 4th metatarsal head area (t=3.33, P=0.01) of the affected side. (2) During the single leg standing, the CAI individuals showed significantly worse balance control in the anterior/posterior direction (P < 0.05) and lateral/medial direction (P < 0.05) compared with the healthy controls, and the affected side had more severe balance control deficit in the lateral/medial direction (P < 0.05). (3) The women (P < 0.05) and the individuals with higher Beighton scores (P < 0.05) showed worse balance control deficit in the lateral/medial direction.@*CONCLUSION@#CAI individuals showed significantly a more lateral shifted plantar distribution during the level walking compared with the healthy individuals and the tendency was worse on the affected sides, and showed worse balance control in the anterior/posterior direction and lateral/medial direction during the single leg standing. The women and those with generalized ligament laxity showed significantly worse balance control.

Advances in molecular pathogenesis and treatment of intrahepatic cholangiocarcinoma / 中华消化外科杂志

Intrahepatic cholangiocarcinoma (ICC) is a group of adenocarcinoma that derives from epithelium of the subbranches of intrahepatic bile ducts, which is characterized by difficulty in early diagnosis, high malignancy and poor prognosis. ICC is relatively rare, but it is the second most common in primary liver cancer, and its incidence has gradually increased worldwide. Radical resection is recognized as the only treatment that can bring better long-term survival currently. However, many surgery-related problems, such as lymph node dissection and major vascular resection and reconstruction, are still controversial. Adjuvant therapy, including chemotherapy, regional therapy, targeted therapy and immunotherapy, has received increasing attention in recent years. Although there is no uniform standard, a large number of related studies have supported its efficacy. In this article, the authors have reviewed the molecular pathogenesis of ICC and advances in treatment.

Berberine ameliorates dexamethasone-induced metabolic disorder in C57 mice / 药学学报

The aim of this study was to evaluate the effects and mechanisms of berberine (BBR) against dexamethasone (Dex)-induced metabolic disorders. 3T3-L1 cells were differentiated by Dex treatment and then treated with BBR (2.5, 5, 10 μmol·L-1). Lipid accumulation was detected using oil-red O staining. After review and approval of the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, C57BL/6N mice were randomly divided into three groups. In the BBR treatment group, mice were subcutaneously implanted with an osmotic pump containing Dex and gavaged with BBR (100 mg·kg-1·day-1) for 4 weeks. The model control group was implanted with a Dex osmotic pump with no other treatment. Mice given a saline-filled osmotic pump were used as a negative control. During the study, food intake and body weight were measured weekly. Subcutaneous fat and visceral fat was detected by MRI. At the end of the experiment the plasma levels of total cholesterol (CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), glucose (Glu), and muscle mass were measured. The expression of peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase α (AMPKα) in 3T3-L1 cells and epididymal fat of C57BL/6N mice was evaluated through RT-PCR and Western blot analysis. The results showed that BBR inhibited Dex-induced adipocyte differentiation in 3T3-L1 preadipocytes by up to 23% in a dose-dependent manner. In C57BL/6N mice, berberine alleviated hyperlipidemia and hyperglycemia and reduced visceral fat accumulation induced by Dex. The results from RT-PCR and Western blot analysis showed that BBR reduced PPARγ expression and increased the phosphorylation of AMPKα in 3T3-L1 cells as well as in adipose tissue. Berberine might alleviate Dex-induced metabolic disorder and visceral fat accumulation by modulating PPARγ and AMPK expression.

Apatinib Combined with Local Irradiation Leads to Systemic TumorControl via Reversal of Immunosuppressive Tumor Microenvironmentin Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to investigate the potential systemic antitumor effects of stereotactic ablativeradiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. @*Materials and Methods@#Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor;irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grewto the touchable size, mice were randomly divided into eight treatment groups. These groupsreceived normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not tothe primary tumor. The further tumor growth/regression of mice were followed andobserved. @*Results@#For the single 15 Gy modality, tumor growth delay could only be observed at the primarytumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primaryand secondary tumor growth could be observed, indicated an abscopal effect wasinduced. Mechanism analysis suggested that programmed death-ligand 1 expressionincreased with SABR was counteract by additional apatinib therapy. Furthermore, whenapatinib was combined with SABR, the composition of immune cells could be changed.More importantly, this two-pronged approach evoked tumor antigen–specific immune responsesand the mice were resistant to another tumor rechallenge, finally, long-term survivalwas improved. @*Conclusion@#Our results suggested that the tumor microenvironment could be managed with apatinib,which was effective in eliciting an abscopal effect induced by SABR.

Robot-assisted unilateral-decompression minimally invasive transforaminal lumbar interbody fusion for radiographic bilateral lumbar stenosis / 中国组织工程研究

BACKGROUND: In the elderly patients with degenerative lumbar spinal stenosis, bilateral nerve root canal stenosis commonly shows only one side of symptoms. There is still controversy about whether or not decompression is needed on the side without symptoms or with less symptoms and how to operate. OBJECTIVE: To explore the safety and efficacy of robot-assisted unilateral-decompression using minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) technique by investigating a series of cases with the radiographic bilateral lumbar canal stenosis presenting with unilateral symptoms and by comparing clinical decompression effect and imaging changes before and after operation. METHODS: Cases with radiographic bilateral lumbar canal stenosis presenting with unilateral symptoms subjected to unilateral decompression on the affected side, interbody fusion and bilateral fixation after robot-assisted MIS-TLIF in the same treatment group were retrospectively analyzed. Operation time, intraoperative blood loss and complications were recorded. The vertebral canal cross-sectional area, intervertebral foramen height, intervertebral space height, and lumbar lordosis angle were examined before and after surgery. Visual analogue scale scores for low back pain and leg pain were assessed before and after surgery. Oswestry disability index was used to assess lumbar function before and after surgery. Macnab criteria were used to evaluate the efficacy at the final follow-up after surgery. RESULTS AND CONCLUSION: (1) Operation time was 110-235 minutes, averagely 169.4 minutes. Intraoperative blood loss was 70-180 mL, averagely 112.4 mL. (2) After 3-8 months of follow-up, the visual analogue scale scores of low back pain and lower extremity pain 1 month after surgery and in final follow-up were significantly lower than those before operation (both P 0.05). (6) It is concluded that robot-assisted unilateral-decompression MIS-TLIF obtained satisfactory effect in bilateral lumbar canal stenosis patients presenting with unilateral symptoms.

Advances in pharmacological effects of higenamine on cardiovascular system / 药学学报

Higenamine (HG) is an active cardiotonic component isolated from Aconite. Chinese and foreign scholars have done a lot of research on the metabolism and pharmacological effects of HG, which confirmed that it has cardiovascular pharmacological effects of cardiactonic action and vasodilation for the treatment of heart failure and bradycardia, anti-oxidative and anti-apoptotic effects which can be used to protect the heart and reduce heart ischemia and reperfusion injury. In addition, HG inhibits the expression of iNOS mRNA by inhibiting the activity of the transcription factor NF-κB, inhibits the lipopolysaccharide (LPS)-induced NO product, and inhibits platelet aggregation and thrombus formation, thereby improving the experimental septic shock in animals. This article reviews the recent progress in cardiovasular pharmacology of HG, which will contribute to the further development and clinical application of it in the future.

Role of gut microbiota in the treatment of nonalcoholic fatty liver disease with traditional Chinese medicine / 药学学报

Nonalcoholic fatty liver disease (NAFLD) is a genetic and environmental factor-associated metabolic disease that can lead to fibrosis, cirrhosis and hepatocellular carcinoma. In recent decades the prevalence of NAFLD has increased, but effective pharmacotherapy is limited. Treatment regimens in traditional Chinese medicine (TCM) have made significant contributions to the control of NAFLD, but underlying mechanisms are far less elucidated. Increasing evidence suggests that gut microbiota play a crucial role in the pathogenesis and development of diseases including NAFLD. The outcomes of such research open a new approach in identifying the molecular mechanisms of TCM. Here we review the evidence that gut microbiota might be a target in the treatment NAFLD using TCM.