Research progress on the material basis and pharmacological effects of Pien Tze Huang / 药学学报

The medicinal history of Pien Tze Huang is long, and it is the only "double top secret" variety of technology and formula at present. It has the effects of clearing heat and detoxifying, detumescence and pain, cooling blood and removing blood stasis. At present, researchers have analyzed and identified some compounds in Pien Tze Huang and its precious medicinal materials, such as Panax notoginseng, calculus bovis, snake gall and musk, and conducted activity screening, pharmacokinetics and pharmacological related studies on these chemical components. It was found that Pien Tze Huang had a significant effect on the treatment of acute and chronic hepatitis, ulcer, colon cancer, liver cancer and other diseases. The purpose of this paper is to systematically discuss the research achievements of researchers in recent years on the material basis, pharmacological effects and clinical application of Pien Tze Huang, with a view to providing ideas for the further research of Pien Tze Huang.

Clinical Analysis of SET-NUP214 Fusion Gene Positive Patients with Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene.@*METHODS@#The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively.@*RESULTS@#Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive.@*CONCLUSION@#The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.

Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

Silybin alleviates hepatic lipid accumulation in methionine-choline deficient diet-induced nonalcoholic fatty liver disease in mice via peroxisome proliferator-activated receptor α / 中国天然药物

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.

Therapeutic effects of herbal formula Huangqisan on metabolic disorders via SREBF1, SCD1 and AMPK signaling pathway / 中西医结合学报

OBJECTIVE@#Metabolic syndrome is a complex medical condition that has become an alarming epidemic, but an effective therapy for this disease is still lacking. The use of the herbal formula Huangqisan (HQS) to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.; however, its therapeutic effects and underlying mechanisms remain elusive.@*METHODS@#To investigate the beneficial effects of HQS on metabolic disorders, high-fat diet-induced obesity (DIO), leptin receptor dysfunction (db/db) and low-density lipoprotein receptor-knockout (LDLR@*RESULTS@#HQS lowered body weight, fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice (P < 0.05). HQS also blocked atherosclerotic plaque formation in LDLR@*CONCLUSION@#HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.

The mechanism of androgen independent signaling pathway in castration-resistant prostate cancer and the research progress on related drugs / 药学学报

Prostate cancer is one of the common malignant tumors of male urogenital system, and the incidence of prostate cancer in China has increased significantly in the past decade. At present, endocrine therapy based on androgen blockade is the main method of clinical treatment except radical surgery and radiotherapy/chemotherapy for prostate cancer. However, the clinical benefit can only be obtained in the early stage of treatment, and nearly 90% of patients will develop to the castration resistance, and among them, nearly 90% of patients will have bone metastasis. The quality of life decreases sharply with the progression of disease for patients. In addition to the androgen signal pathway, studies have shown that many other oncogenic signal pathways have involved in the development of castration resistance, including classic cancer signaling pathways, immune and inflammatory signaling pathways, etc. Understanding the mechanism of androgen independent signal pathway in the formation of castration resistance will help to understand the off-target effect of androgen blocking therapy and introduce new treatment targets or strategies to get rid of the "no drug available" dilemma for clinical treatment of castration resistance.

Effects of booster vaccination with tetanus toxoid, reduced diphtheria and acellular pertussis combined vaccine (Tdap) after vaccination of rats with DTacP-sIPV or DTacP-IPV/Hib / 中华微生物学和免疫学杂志

Objective:To evaluate the effects of a booster immunization with a candidate tetanus toxoid, reduced diphtheria toxoid and acellular pertussis combined vaccine (Tdap) in a rat model after primary vaccination with diphtheria, tetanus, acellular pertussis and Sabin strain inactivated poliovirus combined vaccine (DTacP-sIPV) or diphtheria, tetanus, acellular pertussis, inactivated poliovirus and haemophilus type b combined vaccine (DTacP-IPV/Hib) for further preclinical study.Methods:Wistar rats were randomly divided into three groups and respectively immunized with a self-developed DTacP-sIPV, a marketed DTacP-IPV/Hib and normal saline at 0, 1, and 2 months of age. Serum levels of antibody against each component in each group were detected before immunization and after each dose. A booster dose of the candidate Tdap was given 10 months after primary immunization. Serum levels of antibody against each component in each group were detected before, 1 month and 6 months after the booster immunization.Results:One month after three doses of primary immunization, the geometric mean titers (GMT, Log2) of antibodies against diphtheria toxoid (DT), tetanus toxoid (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) in the DTacP-sIPV group were 17.41, 18.34, 18.11, 19.93 and 13.91, respectively, and the seroconversion rates of these components all reached 100%. Ten months after primary immunization, the GMTs of antibodies against DT, TT, PT, FHA and PRN decreased to 15.17, 14.26, 13.60, 14.51 and 10.39, respectively, and the seroconversion rates remained above 89%. One month after booster immunization, the GMTs of antibodies against DT, TT, PT and FHA in the DTacP-sIPV and DTacP-IPV/Hib groups were 16.49/17.26, 16.80/17.63, 16.70/17.74 and 18.48/19.26, respectively, and the seroconversion rates of these components all reached 100% with no significant difference between the two groups ( P>0.05). The GMTs of anti-PRN antibody in the DTacP-sIPV and DTacP-IPV/Hib groups were 13.07 and 11.00, and the seroconversion rates were 100% and 88%, which were higher in the DTacP-sIPV group than in the DTacP-IPV/Hib group ( P<0.05). Six months after booster immunization, the GMTs of antibodies against DT, TT, PT, FHA and PRN in the DTacP-sIPV and DTacP-IPV/Hib groups decreased to 15.74/14.87, 15.07/15.14, 14.84/15.73, 16.62/16.37 and 11.44/9.96, respectively, and the seroconversion rates remained above 88%. Conclusions:Booster vaccination with the candidate Tdap vaccine induces humoral immune response following primary immunization with DTacP-sIPV or DTacP-IPV/Hib in the Wistar rat model, while the antibody titer decreases with time.

Cerebrotendinous xanthomatosis： a family report and literature review / 中华神经科杂志

Objective:To summarize and review a Chinese family with cerebrotendinous xanthomatosis (CTX) so as to improve understanding of the disease.Methods:The proband was admitted to the Department of Neurology， the Second Hospital of Hebei Medical University on May 30, 2019. The medical history, neuro-imaging, pathology, CYP27A1 gene of the proband and CYP27A1 gene of her family were analyzed. Clinical features of similar cases from published literatures were retrieved and systematically summarized.Results:The proband was a 39-year-old female who was admitted to the Second Hospital of Hebei Medical University due to weakness of both lower limbs lasted for more than five years and aggravated for one year with speech slurred. The proband manifested with mental retardation, bilateral pyramidal tract impairment and cerebellar lesions, and had cholesterol crystal in xanthomas and compound heterozygous mutations of c.435G>A and c.1263+1G>A in CYP27A1 gene. The proband′s sister had the same mutation as the proband′s. The proband′s mother was the carrier of c.435G>A mutation, and father was the carrier of c.1263+1G>A mutation. Seventeen related cases concerning CTX with detailed clinical data were searched with major domestic databases. Combined with this case, clinical features with the frequency more than 50% were pyramidal sign, mental decline, ataxia, dysarthria, achilles tendon neoplasm, cataract, high arch foot.Conclusions:The onset of CTX is hidden, which can be diagnosed by its pathology and CYP27A1 gene detection. The possibility of CTX should be considered when there are unexplained clinical manifestations in common diseases such as pyramidal sign, mental decline, ataxia, dysarthria, achilles tendon neoplasm, cataract, high arch foot and so on.

Efficacy of Arsenic Trioxide Combined with ATRA and Chemotherapy for Relapsed Acute Promyelocytic Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients.@*METHODS@#The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed.@*RESULTS@#Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications.@*CONCLUSION@#For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.

Effect of two kinds of surface pretreatments on bending strength to the modified polyetheretherketone / 华西口腔医学杂志

OBJECTIVE@#To evaluate the effect of sandblasting or acid etching on the three-point bending strength to the modified polyetheretherketone (PEEK).@*METHODS@#Forty-eight bars (15 mm×2 mm×1 mm) of specimens were fabricated from the modified PEEK (BioHPP). They were randomly divided into the following groups: A, B, C and D groups, which were blasted with alumina particles; E, F, and G groups, which were etched with 98% concentrated sulfuric acid; and control group H. The sand blast pressure of groups A, B and C was 0.2 MPa, and the grain sizes of the sand blasted were 120, 50, and 250 µm, respectively. Group D was blasted with 120 µm particle size at 0.7 MPa pressure. Groups E, F and G were acid etched for 60, 120, and 300 s, respectively. No surface treatment was conducted in group H. After all the specimens were processed, one sample was randomly selected from each group to observe its surface morphology under a scanning electron microscope (SEM), and the other specimens were tested for their three-point bending strength. SPSS 22.0 software was used to analyze the experimental data and to test whether the difference was statistically significant.@*RESULTS@#SEM observation showed that the surface morphology of the specimen changed after the treatment and revealed different degrees of cracks, pits, or voids. The three-point bending test indicated that the strength of the specimens treated with sandblasting or concentrated sulfuric acid decreased compared with that of the control group (P0.05). The strength of group D was lower than that of group A at the same particle size (P0.05).@*CONCLUSIONS@#The bending strength of BioHPP could be significantly decreased by surface sand blasting or concentrated sulfate etching as the sandblasting pressure increased, but the bending strength did not decrease as sand particle size and acid etching time changed.

Determination of Dissolution of Inhaled Drugs by Paddle Apparatus Method / 中国药学杂志

OBJECTIVE: To develop a method for determination of the dissolution of inhaled drugs by using indacaterol maleate, ipratropium bromide and budesonide as model drugs, and explore the law of dissolution of inhaled drugs. METHODS: Samples were prepared and the improved paddle apparatus method (USP dissolution assay-fifth method) was used for dissolution experiment. Samples were taken at a certain time, and the drug concentration was determined by HPLC. The sample dispersion method, dissolution medium and membrane were optimized, meanwhile inhaled drugs with different properties were measured and dissolution curve was modeled. RESULTS: An improved paddle apparatus method for simulating drug dissolution in respiratory tract was developed, samples were collected using the new generation impactor and the dissolution parameters were determined to be as follows: 150 mL of dissolution medium (250 mL dissolution cup), 2% Tween 80-PBS dissolution medium, 4.5 cm watch glass (4.7 cm drug-loaded membranes and 4.7 cm mesh screen), glass microfiber filters, double-layer membranes, drug-loaded membrane fixation method (level the mesh screen) and sampling time of 3 h; Weibull model was suitable for fitting the three drugs with different solubility (r2>0.999 1). CONCLUSION: The method is simple and reproducible, and can be used to determine the dissolution of inhalation drugs; the dissolution process of inhaled drugs is consistent with Weibull model.

A hepatoprotection study of Radix Bupleuri on acetaminophen-induced liver injury based on CYP450 inhibition / 中国天然药物

We investigated the potential hepatoprotective effect of Radix Bupleuri (RB) by inducing acute liver injury (ALI) in an animal model using acetaminophen (APAP) after pretreatment with RB aqueous extract for three consecutive days. Compared to those of the APAP group, the biochemical and histological results of the RB pretreatment group showed lower serumaspartate transaminase (AST) and alanine transaminase (ALT) levels as well as less liver damage. Pharmacokinetic study of the toxicity related marker acetaminophen-cysteine (APC) revealed a lower exposure level in rats, suggesting that RB alleviated APAP-induced liver damage by preventing glutathione (GSH) depletion. The results of cocktail approach showed significant inhibition of CYP2E1 and CYP3A activity. Further investigation revealed the increasing of CYP2E1 and CYP3A protein was significantly inhibited in pretreatment group, while no obvious effect on gene expression was found. Therefore, this study clearly demonstrates that RB exhibited significant protective action against APAP-induced acute live injury via pretreatment, and which is partly through inhibiting the increase of activity and translation of cytochrome P450 enzymes, rather than gene transcription.

Current status and future prospect of pharmacotherapy for pancreatic cancer / 中国中药杂志

Pancreatic cancer is the most common digestive tract tumor with an increasing incidence in recent years. The poor prognosis of pancreatic cancer is mainly because of the inability of detecting tumor at an early stage,its high potential for early dissemination,and its relatively poor sensitivity to chemotherapy. Most patients have lost the opportunity for surgery when they are diagnosed,which resulted in an urgent need for the development of more effective and safe therapies for pancreatic cancer. However,the current clinical cancer chemotherapy based on gemcitabine leads to poor prognosis in pancreatic patients. With the continuous research on the biological and cellular signaling pathways of pancreatic cancer,there have emerged a great many of novel agents,including new chemotherapeutic,targetable and immune-modulatory drugs,and some drugs have achieved encouraging results. Furthermore,as an alternative and supplementary method,traditional Chinese medicine has shown good application prospects in the field of pancreatic cancer treatment. This article reviews the current status of drug therapy for pancreatic cancer,summarizes the strength and weakness of existing therapeutic drugs in the application process,gives prospects of possible breakthroughs for the pharmacotherapy in the future,and provides certain new ideas and lessons for subsequent drug development.

Anti-lung cancer mechanisms of diterpenoid tanshinone via endoplasmic reticulum stress-mediated apoptosis signal pathway / 中国中药杂志

At present, lung cancer ranks second and first respectively in the incidence and the mortality among malignant tumors. It is urgent to find new effective anti-lung cancer drugs with less side effects and relatively defined mechanisms. Endoplasmic reticulum stress (ERS)-mediated apoptosis pathway is an effective way to promote tumor cell apoptosis; diterpenoid tanshinone (DT), an effective part separated from Salviae Miltiorrhizae Radix et Rhizoma, was found to have an anti-lung cancer effect in previous studies via ERS-induced PERK-EIF2α pathway. In this paper, human lung adenocarcinoma PC9 cell line and nude mouse transplantation tumor model were applied to verify the anti-lung cancer effect of DT in vivo and in vitro, and illuminate the potential mechanism via ERS induced IRE1α/caspase 12 apoptosis pathway. The results showed that in vivo, DT could promote PC9 cell apoptosis in a concentration-dependent manner, up-regulate Bip, IRE1 and TRAF2 protein expressions in tumor tissue, reduce tumor weight and alleviate bodyweight loss. In vitro, DT inhibited the proliferation of PC9 cell line in a concentration-dependent manner, and destroyed the structure of mitochondria in PC9 cell, promoted Bax, IRE1α, Bip, TRAF2 and caspase 12 protein expressions, lower Bcl-2 protein expression in a time-dependent manner. DT shows a good effect on anti-lung cancer both in vivo and in vitro. The mechanism is related to the activation of ERS-induced IRE1α/caspase 12 apoptosis pathway and the promotion of cell apoptosis. ERS-mediated apoptosis pathway may be an important target of DT on anti-lung cancer.

The effect of preoperative prehabilitation on nutritional status and body composition of patients with esophageal cancer after operation / 肠外与肠内营养

Objective: To observe the efficacy of preoperative prehabilitation on nutritional status and body composition of patients with esophageal cancer after operation. Methods: A total of 100 patients with esophageal cancer were randomly divided into the study group A and the control group B. The study group received prehabilitation from the day they adimitted to hospital and the control group received common preoperative preparation. The preoperative baseline data and postoperative indicators including levels of serum albumin, prealbumin, transferrin were recorded the day admitted to hospital and the 1, 3, 7, 30th day after surgery. Record the prognosis of the patients (albumin supplementation, incidence of postoperative complications, ICU monitoring time, total cost of hospitalization). And the body composition was examined on the day admitted to hospital and the 7, 30th day after surgery with BIA. Results: The level of serum albumin, prealbumin, transferrin and body composition were no statistically significant difference between the study group and the control group. Compared with the control group, the level of prealbumin were significantly higher in the study group on the 1, 3, 7, 30th day after surgery. The level of serum albumin, transferrin were also significantly higher in study group on the 3, 7, 30th day after surgery. The body composition was no significant difference between the two groups on the 7th day postoperatively. However, the loss of body composition such as skeletal muscle, body water, intracellular water, protein level and body cell volume were less in the study group compared with the control group on the 30th day after surgery. The incidence of postoperative complications in the prehabilitation group, ICU monitoring time, and hospitalization costs were significantly less than those in the control group. Conclusion: Prehabilitation intervention can obviously improve the nutritional status and the prognosis of the patients with esophageal cancer, and reduce the loss degree of their body composition.

Primary Prophylatic Effect of Voriconazole Against Invasive Infection of Pulmonary Aspergillosis during Remission-Induction Chemotherapy for Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of primary prophylaxis of voriconazole against invasive infection of pulmonary aspergillosis (IPA) during remission-induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>Clinical data of 102 de novo AML patients who received primary anti-IPA prophylaxis during the first induction chemotherapy were analyzed retrospectively. All the cases were divided into voriconazole-treated group and posaconazole-treated group according to the prophylactic agent. The incidences of IPA and systemic antifungal treatment during induction chemotherapy were analyzed for both groups.</p><p><b>RESULTS</b>Among 102 enrolled cases, 42 cases received voriconazole and other 60 received posaconazole as primary prophylaxis. IPA occurred in 3 cases of voriconazole group (1 probable, 2 possible); IPA occurred in 4 cases of posaconazose group, and all were possible cases. The incidence of IPA during remission-induction chemotherapy in variconazole group equaled to posaconazose group (7.1% vs. 6.7%) (P=0.925). Beside IPA cases, 2 cases in voriconazole group and 4 cases in posaconazole group received intravenous anti aspergillosis drugs preemptive treatment, and no significant difference of prophylactic success rate was observed between two groups (88.1% vs. 86.7%) (P=0.831). Visual disturbance was the most common adverse event occurred in voriconazole group, but no significant differences of incidences of other adverse effects were observed when compared with posaconazole group.</p><p><b>CONCLUSION</b>According to similar prophylactic effect with posaconazole, voriconazole appears to be a good alternative for primary prophylaxis of IPA during remission-induction chemotherapy in AML patients.</p>

Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs / 中国天然药物

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg).

Update on immune and metabolic dysregulation in major depressive disorder and the implications for drug intervention / 药学学报

Traditional anti-depressant therapy based on the regulation of monoamine neurotransmitters has shown certain limitations. Recently, accumulating clinical and preclinical studies have reported the tantalizing link between immune dysregulation, inflammatory process and the initiation and exacerbation of major depressive disorder (MDD). With a deepening understanding of neural-immune-metabolic interactions, an immunometabolism driven disease network has attracted huge interests in understanding neuronal inflammation and dysfunction underlying MDD pathogenesis and intervention. This review describes recent data uncovering immunometabolic dysregulation as a key factor in MDD network, with a focus on the recent appreciation of immune-metabolic actions of several anti-depressant compounds. The implications for the discovery of novel antidepressant drugs and clinical management of MDD are discussed.

Comparative pharmacokinetic study of vonoprazan in acute hepatic injury rats and normal rats / 药学学报

Hepatic disease is one of the high-prevalence diseases in China, of which gastrointestinal bleeding is a common complication treated by proton pump inhibitors. Vonoprazan is a novel proton pump inhibitor which acts better than lansoprazole in pharmacokinetics and pharmacodynamics. In this study, the pharmacokinetics of vonoprazan was compared between acute hepatic injury and normal condition in rats. Results showed that the exposure (AUC) of vonoprazan was significantly higher in rats with acute hepatic injury than in normal rats, and the metabolites formation rates of vonoprazan also slowed down, which might be due to the change of activity of enzymes and transporters. This find may provide a theoretical basis for the dose regulation of vonoprazan in patients with hepatic injury.